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Karim Parastouei Mohammad Hossein Aarabi Gholam Ali Hamidi Zahra Nasehi Shima Kabiri-Arani Faezeh Jozi Mohammad Esmaeil Shahaboddin 《Reports of Biochemistry & Molecular Biology》2022,11(1):1
Background:Cannabinoids (CBs) have been found to regulate the immune system, affect innate and adaptive immune responses, and reduce inflammatory reactions. This study assessed the therapeutic effects of GW-405833 synthetic CB2 agonist on inflammatory factors as well as locomotor activity in experimental autoimmune encephalomyelitis (EAE).Methods:In this experimental study, 48 adult male C57BL/6 mice were randomly and equally assigned to eight groups. By injecting 250 mg of MOG35-55 peptide, EAE was induced. Every other day for 17 days after EAE onset, EAE-afflicted mice in groups 1–3 received an intraperitoneal injection of GW-405833 at a dose of 3, 10, and 30 mg/kg, respectively. Clinical status and locomotor activity, measured using the beam walking assay, were assessed every other day during the first 17 days after EAE onset. Mice were euthanized in day 17th of treatment and the serum levels of the IL-1β, IL-12, CRP, and TNF-α proinflammatory cytokines as well as IL-4 and TGF-β anti-inflammatory cytokines were measured by ELISA method.Results:Clinical manifestations of EAE in groups 2 and 3 were significantly milder than group 4 and locomotor activity in groups 1–3 was significantly better than group 4 in days 5–17 (p< 0.05). GW-405833 also significantly decreased the levels of IL-12, TNF-α, and CRP and significantly increased the levels of IL-4 and TGF-β but had no significant effects on the level of IL-1β. GW-405833 was not associated with significant side effects.Conclusion:The CB2 receptor agonist GW-405833, improves clinical conditions and reduces inflammation in mice with EAE.Key Words: Clinical evaluation, Experimental autoimmune encephalomyelitis, GW-405833, Locomotor activity, Multiple sclerosis, Proinflammatory cytokines 相似文献
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Andrea Irazoki Marta MartinezVicente Pilar Aparicio Cecilia Aris Esmaeil Alibakhshi Maria RubioValera Juan Castellanos Luis Lores Manuel Palacín Anna Gum Antonio Zorzano David Sebastin 《Aging cell》2022,21(4)
Sarcopenia is one of the main factors contributing to the disability of aged people. Among the possible molecular determinants of sarcopenia, increasing evidences suggest that chronic inflammation contributes to its development. However, a key unresolved question is the nature of the factors that drive inflammation during aging and that participate in the development of sarcopenia. In this regard, mitochondrial dysfunction and alterations in mitophagy induce inflammatory responses in a wide range of cells and tissues. However, whether accumulation of damaged mitochondria (MIT) in muscle could trigger inflammation in the context of aging is still unknown. Here, we demonstrate that BCL2 interacting protein 3 (BNIP3) plays a key role in the control of mitochondrial and lysosomal homeostasis, and mitigates muscle inflammation and atrophy during aging. We show that muscle BNIP3 expression increases during aging in mice and in some humans. BNIP3 deficiency alters mitochondrial function, decreases mitophagic flux and, surprisingly, induces lysosomal dysfunction, leading to an upregulation of Toll‐like receptor 9 (TLR9)‐dependent inflammation and activation of the NLRP3 (nucleotide‐binding oligomerization domain (NOD)‐, leucine‐rich repeat (LRR)‐, and pyrin domain‐containing protein 3) inflammasome in muscle cells and mouse muscle. Importantly, downregulation of muscle BNIP3 in aged mice exacerbates inflammation and muscle atrophy, and high BNIP3 expression in aged human subjects associates with a low inflammatory profile, suggesting a protective role for BNIP3 against age‐induced muscle inflammation in mice and humans. Taken together, our data allow us to propose a new adaptive mechanism involving the mitophagy protein BNIP3, which links mitochondrial and lysosomal homeostasis with inflammation and is key to maintaining muscle health during aging. 相似文献
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A novel recombinant anti‐epidermal growth factor receptor peptide vaccine capable of active immunization and reduction of tumor volume in a mouse model
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Majid Asadi‐Ghalehni Mohamad Javad Rasaee Masoumeh RajabiBazl Masood Khosravani Majid Motaghinejad Masoud Javanmardi Saeed Khalili Helmout Modjtahedi Esmaeil Sadroddiny 《Microbiology and immunology》2017,61(12):531-538
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Esmaeil Nezami-Alanagh Ghasem-Ali Garoosi Sara Maleki Mariana Landín Pedro Pablo Gallego 《Plant Cell, Tissue and Organ Culture》2017,129(1):19-33
In this study, artificial intelligence techniques—specifically artificial neural networks (ANNs) in combination with fuzzy logic (neurofuzzy logic) or with genetic algorithms (ANNs–GA)—have been employed, as modeling tools, to get insight, to predict and to optimize the effect of several independent factors on four growth parameters during Pistacia vera micropropagation. Twenty-six media ingredients, including mineral ions (or salts), glycine, vitamins and plant growth regulators (PGRs) at different concentrations, were used as inputs and four growth parameters: proliferation rate, shoot length, total and healthy fresh weight as outputs on the models. The IF-THEN rules from neurofuzzy logic models have allowed discovering the positive (BAP, nicotinic-acid and pyridoxine-HCl) and negative (NO3 ?, Mg2+, Ag+ and gluconate?) effects on the growth parameters and the fundamental role of BAP over all of them. Also, ANNs–GA technology has permitted to estimate the best combination of media ingredients to simultaneously maximize the four parameters of growth: 4.4 new shoots per explant; 28.7 mm length; 1.1 and 0.53 g total and healthy fresh weight, respectively, minimizing physiological disorders. In our opinion, the information obtained in this study is extremely useful to improve the massive multiplication of pistachio plant, in particular, but also demonstrate the ability of artificial intelligence technology to design plant tissue culture media with predictable and tailorable characteristics. 相似文献
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Esmaeil Davoodi-Bojd Michael Chopp Hamid Soltanian-Zadeh Shiyang Wang Guangliang Ding Quan Jiang 《PloS one》2014,9(5)
Substantial effort is being expended on using micro-structural modeling of the white matter, with the goal of relating diffusion weighted magnetic resonance imaging (DWMRI) to the underlying structure of the tissue, such as axonal density. However, one of the important parameters affecting diffusion is the water exchange rate between the intra- and extra-axonal space, which has not been fully investigated and is a crucial marker of brain injury such as multiple sclerosis (MS), stroke, and traumatic brain injury (TBI). To our knowledge, there is no diffusion analytical model which includes the Water eXchange Rate (WXR) without the requirement of short gradient pulse (SGP) approximation. We therefore propose a new analytical model by deriving the diffusion signal for a permeable cylinder, assuming a clinically feasible pulse gradient spin echo (PGSE) sequence. Simulations based on Markov Random Walk confirm that the exchange parameter included in our model has a linear correlation (R2>0.88) with the actual WXR. Moreover, increasing WXR causes the estimated values of diameter and volume fraction of the cylinders to increase and decrease, respectively, which is consistent with our findings from histology measurements in tissues near TBI regions. This model was also applied to the diffusion signal acquired from ex vivo brains of 14 male (10 TBI and 4 normal) rats using hybrid diffusion imaging. The estimated values of axon diameter and axonal volume fraction are in agreement with their corresponding histological measurements in normal brains, with 0.96 intra-class correlation coefficient value resulting from consistency analysis. Moreover, a significant increase (p = 0.001) in WXR and diameter and decrease in axonal volume fraction in the TBI boundary were detected in the TBI rats compared with the normal rats. 相似文献
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Formin proteins direct the nucleation and assembly of linear actin filaments in a variety of cellular processes using their conserved formin homology 2 (FH2) domain. Diaphanous-related formins (DRFs) are effectors of Rho-family GTPases, and in the absence of Rho activation they are maintained in an inactive state by intramolecular interactions between their regulatory N-terminal region and a C-terminal segment referred to as the DAD domain. Although structures are available for the isolated DAD segment in complex with the interacting region in the N-terminus, it remains unclear how this leads to inhibition of actin assembly by the FH2 domain. Here we describe the crystal structure of the N-terminal regulatory region of formin mDia1 in complex with a C-terminal fragment containing both the FH2 and DAD domains. In the crystal structure and in solution, these fragments form a tetrameric complex composed of two interlocking N+C dimers. Formation of the tetramer is likely a consequence of the particular N-terminal construct employed, as we show that a nearly full-length mDia1 protein is dimeric, as are other autoinhibited N+C complexes containing longer N-terminal fragments. The structure provides the first view of the intact C-terminus of a DRF, revealing the relationship of the DAD to the FH2 domain. Delineation of alternative dimeric N+C interactions within the tetramer provides two general models for autoinhibition in intact formins. In both models, engagement of the DAD by the N-terminus is incompatible with actin filament formation on the FH2, and in one model the actin binding surfaces of the FH2 domain are directly blocked by the N-terminus. 相似文献