Microarray analysis identification of key pathways and interaction network of differential gene expressions during osteogenic differentiation

Background: Adult bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stem cells that can differentiate into three lineages. They are suitable sources for cell-based therapy and regenerative medicine applications. This study aims to evaluate the hub genes and key pathways of differentially expressed genes (DEGs) related to osteogenesis by bioinformatics analysis in three different days. The DEGs were derived from the three different days compared with day 0. Results: Gene expression profiles of GSE37558 were obtained from the Gene Expression Omnibus (GEO) database. A total of 4076 DEGs were acquired on days 8, 12, and 25. Gene ontology (GO) enrichment analysis showed that the non-canonical Wnt signaling pathway and lipopolysaccharide (LPS)-mediated signaling pathway were commonly upregulated DEGs for all 3 days. KEGG pathway analysis indicated that the PI3K-Akt and focal adhesion were also commonly upregulated DEGs for all 3 days. Ten hub genes were identified by CytoHubba on days 8, 12, and 25. Then, we focused on the association of these hub genes with the Wnt pathways that had been enriched from the protein-protein interaction (PPI) by the Cytoscape plugin MCODE. Conclusions: These findings suggested further insights into the roles of the PI3K/AKT and Wnt pathways and their association with osteogenesis. In addition, the stem cell microenvironment via growth factors, extracellular matrix (ECM), IGF1, IGF2, LPS, and Wnt most likely affect osteogenesis by PI3K/AKT. © 2020, The Author(s)

Functional differences of Toll-like receptor 4 in osteogenesis, adipogenesis and chondrogenesis in human bone marrow-derived mesenchymal stem cells

Multipotent human bone marrow-derived mesenchymal stem cells (hMSCs) are promising candidates for bone and cartilage regeneration. Toll-like receptor 4 (TLR4) is expressed by hMSCs and is a receptor for both exogenous and endogenous danger signals. TLRs have been shown to possess functional differences based on the species (human or mouse) they are isolated from therefore, the effects of knockdown of TLR4 were evaluated in humans during the differentiation of MSCs into bone, fat and chondrocyte cells in vitro. We investigated the expression profile of TLR4 during the differentiation of hMSCs into three different lineages on days 7, 14 and 21 and assessed the differentiation potential of the cells in the presence of lipopolysaccharide (LPS, as an exogenous agonist) and fibronectin fragment III-1c (FnIII-1c, as an endogenous agonist). TLR4 expression increased following the induction of hMSC differentiation into all three lineages. Alkaline phosphatase activity revealed that FnIII-1c accelerated calcium deposition on day 7, whereas LPS increased calcium deposition on day 14. Chondrogenesis increased in the presence of LPS; however, FnIII-1c acted as a reducer in the late stage. TLR4 silencing led to decreased osteogenesis and increased adipogenesis. Furthermore, Wnt5a expression was inversely related to chondrogenesis during the late stage of differentiation. We suggest that understanding the functionality of TLR4 (in the presence of pathogen or stress signal) during the differentiation of hMSCs into three lineages would be useful for MSC-based treatments. © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd

How Can Selection of Biologically Inspired Features Improve the Performance of a Robust Object Recognition Model?

Humans can effectively and swiftly recognize objects in complex natural scenes. This outstanding ability has motivated many computational object recognition models. Most of these models try to emulate the behavior of this remarkable system. The human visual system hierarchically recognizes objects in several processing stages. Along these stages a set of features with increasing complexity is extracted by different parts of visual system. Elementary features like bars and edges are processed in earlier levels of visual pathway and as far as one goes upper in this pathway more complex features will be spotted. It is an important interrogation in the field of visual processing to see which features of an object are selected and represented by the visual cortex. To address this issue, we extended a hierarchical model, which is motivated by biology, for different object recognition tasks. In this model, a set of object parts, named patches, extracted in the intermediate stages. These object parts are used for training procedure in the model and have an important role in object recognition. These patches are selected indiscriminately from different positions of an image and this can lead to the extraction of non-discriminating patches which eventually may reduce the performance. In the proposed model we used an evolutionary algorithm approach to select a set of informative patches. Our reported results indicate that these patches are more informative than usual random patches. We demonstrate the strength of the proposed model on a range of object recognition tasks. The proposed model outperforms the original model in diverse object recognition tasks. It can be seen from the experiments that selected features are generally particular parts of target images. Our results suggest that selected features which are parts of target objects provide an efficient set for robust object recognition

The Effects of Separate and Combined Stress during Pregnancy on Motor Learning of Offspring of Rats

Abstract: Background & Aims: Today, due to the modern industrial life of human beings, stress has become prevalent among them and they will suffer from its complications. Exposure to stress during pregnancy can change many babies' normal physiological processes. The separate and combined effects of three common types of prenatal stress were investigated on motor learning of male offspring of rats. Methods: In the present study, pregnant NMRI rats were used. Except the control group, the other groups were stressed on the eighth day of gestation for 10 days. The motor learning of 40 male offspring rats were tested using the rotarod performance test 75 days after the experiment. The length of time that each rat could maintain its balance was recorded automatically. The study groups included control, electromagnetic field stress (intensity 1.2 mT, 50 Hz), immobility stress (for 0.5 hour - 2 times/day), social stress (6 rats kept in a small cage), and combined stress (all 3 of the above stresses). Data were analyzed by using multiple comparisons and Tukey’s tests. Results: The motor balance of the combined stress group was lower than the control, at first timing of the first test day (P < 0.05). In the next few days of the test, the effects of stress on learning of experimental groups were not similar. Combined stress reduced motor learning. Learning fluctuations were higher in electromagnetic field stress group compared to the other groups. Conclusion: The results of our study showed that prenatal combined stress can reduce motor learning of children. Keywords: Combined stress, Social stress, Immobility stress, Electromagnetic field, Motor learning, Ra

Effects of crocin on brain oxidative damage and aversive memory in a 6-OHDA model of Parkinson’s disease

ABSTRACT The purpose of the present study was to investigate the effect of crocin on brain oxidative damage and memory deficits in a 6-hydroxydopamine (6-OHDA) model of Parkinson’s disease. Male Wistar rats were subjected to unilateral injection of 6-OHDA (16 µg) into the medial forebrain bundle and treated with crocin (30 and 60 mg/kg) for six weeks. The rats were tested for memory performance at six weeks after 6-OHDA infusion, and then were killed for the estimation of biochemical parameters. The increase in thiobarbituric acid reactive substances (TBARS) and nitrite levels in the hippocampus were observed in the 6-OHDA lesioned rats, which was accompanied by memory deficits in a passive avoidance test at the end of week 6. Moreover, treatment with crocin decreased TBARS and nitrite levels in the hippocampus, and improved aversive memory. The present study conclusively demonstrated that crocin acts as an antioxidant and anti-inflammatory agent in the hippocampus of parkinsonian rats and could improve aversive memory through its properties

Comparison of the Analgesic Effect of Oral Sucrose And/or Music in Preterm Neonates: A Double-blind Randomized Clinical Trial

OBJECTIVE: To compare the analgesic effects of sucrose, music, and their combination on venipuncture\u27s pain in preterm neonates. METHODOLOGY: A double-blinded randomized control trial conducted at a Neonatal Intensive Care Unit (NICU) affiliated to Tehran University of Medical Sciences (TUMS) in Tehran, Iran. One hundred and twenty preterm neonates were randomly allocated into three experimental (sucrose, music and combination of sucrose and music) and one control groups (n = 30 for each group). Two minutes before the venipuncture, 0.5 ml of oral 24% sucrose was provided for the sucrose and combination groups. The combination group additionally received lullaby music as same as the music group. The control group had headphones without playing music and received sterile water. Blinded assessment of the Premature Infant Pain Profile (PIPP) was performed before and during venipuncture, as well as 30 s and 10 min and 10 min after its completion. RESULTS: The pain scores during venipuncture in the sucrose and combination groups were significantly lower than the control group (p = .003, p \u3c .001, respectively) but not in the music group. Thirty seconds after the end of the venipuncture, the pain score in the three intervention groups was significantly lower than the control group (sucrose, music and, combination group, p \u3c .001, p = .009, p \u3c .001, respectively). Ten min after the venipuncture, there was no significant difference in pain scores among the four groups. CONCLUSION: Music could relief pain 30 s after the venipuncture completion but not during the venipuncture. A more prolonged period of playing music is recommended to evaluate the analgesic effects of music in preterm neonates in future studies