Interferon-γ-Treated Mesenchymal Stem Cells Modulate the T Cell-Related Chemokines and Chemokine Receptors in an Animal Model of Experimental Autoimmune Encephalomyelitis.

BACKGROUND: Mesenchymal stem cells (MSCs) modulate immune responses, and their immunomodulatory potential can be enhanced using inflammatory cytokines. Here, the modulatory effects of IFN-γ-licensed MSCs on expression of T cell-related chemokines and chemokine receptors were evaluated using an experimental autoimmune encephalomyelitis (EAE) model. MATERIAL AND METHODS: EAE was induced in 3 groups of C57bl/6 mice and then treated with PBS, MSCs and IFN-γ-treated MSCs. The EAE manifestations were registered daily and finally, the brain and spinal cords were isolated for histopathological and gene expression studies. RESULTS: The clinical scores were lowered in MSCs and IFN-γ-licensed MSCs groups, however, mice treated with IFN-γ-licensed MSCs exhibited lower clinical scores than MSCs-treated mice. Leukocyte infiltration into the brain was reduced after treatment with MSCs or IFN-γ-licensed MSCs compared to untreated group (P<0.05 and P<0.01, respectively). In comparison with untreated EAE mice, treatment with MSCs reduced CCL20 expression (P<0.001) and decreased CXCR3 and CCR6 expression (P<0.02 and P<0.04, respectively). In comparison with untreated EAE mice, treatment with IFN-γ-licensed MSCs reduced CXCL10, CCL17 and CCL20 expression (P<0.05, P<0.05, and P<0.001, respectively) as well as decreased CXCR3 and CCR6 expression (P<0.002 and P<0.02, respectively), whilst promoting expression of CCL22 and its receptor CCR4 (P<0.0001 and P<0.02, respectively). In comparison with MSC-treated group, mice treated with IFN-γ-licensed MSCs exhibited lower CXCL10 and CCR6 expression (P<0.002 and P<0.01, respectively), whereas greater expression of CCL22 and CCR4 (P<0.0001 and P<0.01, respectively). CONCLUSION: Priming the MSC with IFN-γ can be an efficient approach to enhance the immunomodulatory potential of MSCs.

Measurement-outlier robust Kalman filter for discrete-time dynamic systems.

This paper proposes a recursive filter for discrete-time linear dynamic systems subject to output outliers or heavy-tailed noises. First, we introduce a weight matrix in the conventional MAP estimation. It is shown that this matrix plays an influential role in the innovation whitening and asymptotic variance of the modified MAP estimation and, consequently, can be used in outlier detection. Then, we propose two different constrained optimization problems to obtain this weight. These constraints, stemming from environmental noise characteristics, help to obtain the weight matrix more precisely, which increases the filtering performance significantly. In the first approach, we introduce a convex optimization problem to minimize the estimation upper bound of the error covariance matrix. The second approach converts the modified MAP estimation to a min-min optimization problem with a concave cost function. Consequently, to reduce the effect of outliers in estimation, a semidefinite program (SDP) is proposed for outlier detection. At last, simulation results show the effectiveness and verify the performance of the proposed filter for dynamic systems in the presence of measurement outliers.

H∞ filtering for nonlinearly coupled complex networks subjected to unknown varying delays and multiple fading measurements.

In this paper, the robust filtering problem for uncertain complex networks with time-varying state delay and stochastic nonlinear coupling based on H∞ performance criterion is studied. The random connections of coupling nodes are represented by utilizing independent random variables and the multiple fading measurements phenomenon is characterized by introducing diagonal matrices with independent stochastic elements. Moreover, the probabilistic time-varying delays in the measurement outputs are described by white sequences with the Bernoulli distributions. Furthermore, All system's matrices are supposed to have uncertainty and a quadratic bound is assumed for nonlinear part of the network. This bound can be obtained by solving a sum of squares (SOS) optimization problem. By applying the Lyapunov theory, we design a robust filter for each node of the network so that the filtering error system is asymptomatically stable and the H∞ performances are met. Then, the parameters of the filters are achieved by solving a linear matrix inequality (LMI) feasibility problem. Finally, the applicability and performance of the proposed H∞ filtering approach are demonstrated via a practical example.

Inhibitory effects of selected antibiotics on the activities of α-amylase and α-glucosidase: In-vitro, in-vivo and theoretical studies.

Antibiotics are effective drugs that are used to treat infectious diseases either by killing bacteria or slowing down their growth. The well-adapted structural features of antibiotics for the inhibition/activation of enzymes include several available hydrogen bond (H-bond) acceptors and donors, flexible backbone and hydrophobic nature. The substrates of α-amylase and α-glucosidase, known as key absorbing enzymes, have functional groups (OH groups) rembling antibiotics. Given the possibility of developing in diabetics and the significant association between diabetes and infection, the present study was conducted to investigate the influences of tetracycline (TET), kanamycin (KANA), lincomycin (LIN), erythromycin (ERM) and azithromycin (AZM) on α-glucosidase and α-amylase activities with calculating IC50 and Ki values. Also, the efficacy of antibiotics after oral administration was evaluated by analysis of blood glucose concentrations in rats, as well as a molecular docking analysis was explored. α-glucosidase and α-amylase activities were inhibited in a dose dependent fashion by TET with an IC50 of 38.7 ±â€¯1.4 and 47.8 ±â€¯3.2 µM respectively, by KANA with an IC50 of 46.2 ±â€¯1.6 and 65.1 ±â€¯1.6, by LIN with an IC50 of 59.1 ±â€¯2.1 and 51.3 ±â€¯4.1, by ERM with an IC50 of 94.9 ±â€¯4.7 and 65.7 ±â€¯3.8 and by AZM with an IC50 of 69.4 ±â€¯4.4 and 103.6 ±â€¯6.2. Moreover, the Ki values of TET were calculated as 4.4 ±â€¯0.6 and 8.4 ±â€¯0.8 µM for α-glucosidase and α-amylase in a competitive-mode and mixed-mode inhibition. In addition, to communicate with the active site of α-glucosidase and α-amylase respectively, TET presented a binding energy of -9.8 and -8.8 kcal/mol, KANA -7.9 and -7.1, LIN -7.8 and -6.7, ERM -6.8 and -6.4, and AZM -6.4 and -7.5 kcal/mol. In-vivo studies also suggested a decrease in the blood glucose concentration after administering TET compared to the positive controls (P < 0.01). The results obtained from the present research can therefore help the scientific community explore the possible interconnection between the clinical side-effects of antibiotics and their α-glucosidase and α-amylase inhibitory properties, as the target enzymes in hypoglycemia conditions.

Carvacrol ameliorates experimental autoimmune encephalomyelitis through modulating pro- and anti-inflammatory cytokines.

AIM: The inflammatory process is a key step in multiple sclerosis (MS) development. Carvacrol exhibits various anti-inflammatory properties. We aimed to assess the Carvacrol effects on clinical manifestations and production of pro-inflammatory (IFN-γ, IL-6 and IL-17) and anti-inflammatory (TGF-ß, IL-4, and IL-10) cytokines in experimental autoimmune encephalomyelitis (EAE) as MS animal model. MAIN METHODS: EAE mice were treated with 5, 10 mg/kg dose of Carvacrol or vehicle, as the control EAE group, every other day until day-21 post EAE induction. On day22, the leukocyte infiltration within the CNS was estimated using hematoxylin-eosin staining. The cytokine production by splenocytes was determined after in vitro stimulating with myelin oligodendrocyte protein (MOG). KEY FINDINGS: The EAE clinical scores in 5 and 10 mg/kg Carvacrol-treated mice were lower than untreated group (P < 0.001 and P < 0.01, respectively). The amounts of IFN-γ and IL-6 production by splenocytes of 5 and 10 mg/kg Carvacrol-administered mice were lower than control group (P < 0.001, and P < 0.01 for IFN-γ respectively; P ˂ 0.05 for IL-6). Splenocytes of 5 and 10 mg/kg Carvacrol-treated mice produced higher levels of TGF-ß than untreated mice (P < 0.001). in splenocytes of 5 mg/kg Carvacrol-treated group the IL-10 production was higher while IL-17 secretion was lower than control group (both with P < 0.01). SIGNIFICANCE: Carvacrol exhibits modulatory effects on expression of pro- and anti-inflammatory cytokines. It ameliorates EAE clinical and pathological consequences and therefore its potentials may be considered in treating MS patients.

Beneficial effects of Thymus vulgaris extract in experimental autoimmune encephalomyelitis: Clinical, histological and cytokine alterations.

The imbalance between pro and anti-inflammatory cytokines plays an important role in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Thymus vulgaris (thyme) as a traditional medicinal plant has been reported to exert antimicrobial, antioxidant, and anti-inflammatory effects. Therefore, this study evaluated the modulatory effects of Thymus vulgaris on the clinical symptoms, histopathological scores, and the production of some anti-inflammatory (TGF-ß, IL-4, and IL-10) and pro-inflammatory (IFN-γ, IL-6 and IL-17) cytokines in EAE model. EAE was induced by MOG35-55 peptide and mice were treated intra-peritoneally (i.p) with phosphate buffered saline (PBS) in the control group or thyme extract (50 or 100 mg/kg of body weight, every other day) in thyme-treated EAE groups, from day 0 to +21 of post MOG immunization. Mice were sacrificed at day 22, and splenocytes were isolated and re-stimulated in vitro with MOG in order to measure the cytokine production and proliferation of re-stimulated cells by enzyme linked immunosorbent assay (ELISA) method and WST-1 reagent, respectively. The clinical symptoms and histopathological scores of the CNS were lower in thyme-treated than EAE control group. Furthermore, the production of IFN-γ and IL-6 by splenocytes was lower in thyme-treated EAE than in the control group. The production of IL-10 and TGF-ß increased in mice treated with thyme extract compared to the control group. In this study, we showed for the first time that the immunomodulatory effects of Thymus vulgaris in EAE model. Thus, the possible therapeutic potential of thyme for treatment of MS could be considered in future research.

A new approach to predict the strength of high energy materials.

This paper presents a new approach to predict the strength of energetic compounds in which there are important classes of high explosives including nitroaromatics, acyclic and cyclic nitramines, nitrate esters and nitroaliphatics. For C(a)H(b)N(c)O(d) compounds, the ratio of carbon to oxygen atoms and the predicted heat of detonation on the basis of the H(2)O-CO(2) arbitrary have been used to calculate the strength of an explosive. The new model can give good predictions for mentioned energetic compounds as determined by the Trauzl test. The novel correlation will be useful in predicting the strength or power of a new energetic compound that has significant potential in the field of explosives and propellants.