scholarly journals Absorbance or organization into ankylosis: a microarray analysis of haemarthrosis in a sheep model of temporomandibular joint trauma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mai-Ning Jiao ◽  
Tong-Mei Zhang ◽  
Kun Yang ◽  
Zhao-Yuan Xu ◽  
Guan-Meng Zhang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Molecular Level ◽  
Contralateral Side ◽  
Sheep Model ◽  
Tmj Ankylosis ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
Or Organization ◽  
Joint Trauma

Abstract Background Traumatic haemarthrosis was hypothesized to be the etiology of temporomandibular (TMJ) ankylosis. Here, taking haematoma absorbance as a control, we aimed to reveal the molecular mechanisms involved in haematoma organizing into ankylosis using transcriptome microarray profiles. Material/methods Disk removal was performed to building haematoma absorbance (HA) in one side of TMJ, while removal of disk and articular fibrous layers was performed to induced TMJ ankylosis through haematoma organization (HO) in the contralateral side in a sheep model. Haematoma tissues harvested at days 1, 4 and 7 postoperatively were examined by histology, and analyzed by Affymetrix OviGene-1_0-ST microarrays. The DAVID were recruited to perform the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis for the different expression genes (DEGs). The DEGs were also typed into protein–protein interaction (PPI) networks to get the interaction data. Six significant genes screened from PPI analysis, were confirmed by real-time PCR. Results We found 268, 223 and 17 DEGs at least twofold at days 1, 4 and 7, respectively. At day 1, genes promoting collagen ossification (POSTN, BGN, LUM, SPARC), cell proliferation (TGF-β), and osteogenic differentiation of mesenchymal stem cells (BMP-2) were up-regulated in the HO side. At day 4, several genes involved in angiogenesis (KDR, FIT1, TEK) shower higher expression in the HO side. While HA was characterized by a continuous immune and inflammatory reaction. Conclusions Our results provide a comprehensive understanding of the role of haematoma in the onset and progress of TMJ ankylosis. The study will contribute to explaining why few injured TMJs ankylose and most do not from the molecular level.

scholarly journals Absorbance or Organization into Ankylosis: A Microarray Analysis of Haemarthrosis in a Sheep Model of Temporomandibular Joint Trauma

2021 ◽  
Author(s):  
Mai-Ning Jiao ◽  
Tong-Mei Zhang ◽  
Kun Yang ◽  
Zhao-Yuan Xu ◽  
Guan-Meng Zhang ◽  
...  
Keyword(s):  
Temporomandibular Joint ◽  
Molecular Mechanisms ◽  
Contralateral Side ◽  
Sheep Model ◽  
Tmj Ankylosis ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
New Ideas ◽  
Or Organization ◽  
Joint Trauma

Abstract Background: Traumatic haemarthrosis was hypothesized to be the etiology of temporomandibular joint (TMJ) ankylosis. Here, taking haematoma absorbance as a control, we aimed to reveal the molecular mechanisms involved in haematoma organizing into ankylosis using transcriptome microarray profiles.Material/Methods: Disk removal was performed to building haematoma absorbance (HA) in one side of TMJ, while removal of disk and articular fibrous layers was performed to induced TMJ ankylosis through haematoma organization (HO) in the contralateral side in a sheep model. Haematoma tissues harvested at days 1, 4 and 7 postoperatively were examined by histology, and analyzed by Affymetrix OviGene-1_0-ST microarrays. The DAVID were recruited to perform the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis for the different expression genes (DEGs). The DEGs were also typed into protein–protein interaction (PPI) networks to get the interaction data. Six significant genes screened from PPI analysis, were confirmed by real-time PCR.Results: We found 268, 223 and 17 DEGs at least 2-fold at days 1, 4 and 7, respectively. At day 1, genes promoting collagen ossification (POSTN, BGN, LUM, SPARC), cell proliferation (TGF-β), and osteogenic differentiation of mesenchymal stem cells (BMP-2) were up-regulated in the HO side. At day 4, several genes involved in angiogenesis (KDR, FIT1, TEK) shower higher expression in the HO side. While HA was characterized by a continuous immune and inflammatory reaction.Conclusions: Our results provide a comprehensive understanding of the role of haematoma in the onset and progress of TMJ ankylosis. Further study of key genes may provide new ideas for future treatment of the disease.

scholarly journals Molecular Mechanisms of Oxytocin Signaling at the Synaptic Connection

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Jan Bakos ◽  
Annamaria Srancikova ◽  
Tomas Havranek ◽  
Zuzana Bacova
Keyword(s):  
Neurodevelopmental Disorders ◽  
Molecular Mechanisms ◽  
Neuronal Excitability ◽  
Molecular Level ◽  
Short Term ◽  
Oxytocin Receptors ◽  
Potential Therapeutic Intervention ◽  
Early Alteration

Aberrant regulation of oxytocin signaling is associated with the etiology of neurodevelopmental disorders. Synaptic dysfunctions in neurodevelopmental disorders are becoming increasingly known, and their pathogenic mechanisms could be a target of potential therapeutic intervention. Therefore, it is important to pay attention to the role of oxytocin and its receptor in synapse structure, function, and neuron connectivity. An early alteration in oxytocin signaling may disturb neuronal maturation and may have short-term and long-term pathological consequences. At the molecular level, neurodevelopmental disorders include alterations in cytoskeletal rearrangement and neuritogenesis resulting in a diversity of synaptopathies. The presence of oxytocin receptors in the presynaptic and postsynaptic membranes and the direct effects of oxytocin on neuronal excitability by regulating the activity of ion channels in the cell membrane implicate that alterations in oxytocin signaling could be involved in synaptopathies. The ability of oxytocin to modulate neurogenesis, synaptic plasticity, and certain parameters of cytoskeletal arrangement is discussed in the present review.

A Pathway and Network Oriented Approach to Enlighten Molecular Mechanisms of Type 2 Diabetes Using Multiple Association Studies

2020 ◽  
Author(s):  
Burcu Bakir-Gungor ◽  
Miray Unlu Yazici ◽  
Gokhan Goy ◽  
Mustafa Temiz
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Protein Interaction ◽  
Molecular Mechanisms ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
Oriented Approach

AbstractDiabetes Mellitus (DM) is a group of metabolic disorder that is characterized by pancreatic dysfunction in insulin producing beta cells, glucagon secreting alpha cells, and insulin resistance or insulin in-functionality related hyperglycemia. Type 2 Diabetes Mellitus (T2D), which constitutes 90% of the diabetes cases, is a complex multifactorial disease. In the last decade, genome-wide association studies (GWASs) for type 2 diabetes (T2D) successfully pinpointed the genetic variants (typically single nucleotide polymorphisms, SNPs) that associate with disease risk. However, traditional GWASs focus on the ‘the tip of the iceberg’ SNPs, and the SNPs with mild effects are discarded. In order to diminish the burden of multiple testing in GWAS, researchers attempted to evaluate the collective effects of interesting variants. In this regard, pathway-based analyses of GWAS became popular to discover novel multi-genic functional associations. Still, to reveal the unaccounted 85 to 90% of T2D variation, which lies hidden in GWAS datasets, new post-GWAS strategies need to be developed. In this respect, here we reanalyze three meta-analysis data of GWAS in T2D, using the methodology that we have developed to identify disease-associated pathways by combining nominally significant evidence of genetic association with the known biochemical pathways, protein-protein interaction (PPI) networks, and the functional information of selected SNPs. In this research effort, to enlighten the molecular mechanisms underlying T2D development and progress, we integrated different in-silico approaches that proceed in top-down manner and bottom-up manner, and hence presented a comprehensive analysis at protein subnetwork, pathway, and pathway subnetwork levels. Our network and pathway-oriented approach is based on both the significance level of an affected pathway and its topological relationship with its neighbor pathways. Using the mutual information based on the shared genes, the identified protein subnetworks and the affected pathways of each dataset were compared. While, most of the identified pathways recapitulate the pathophysiology of T2D, our results show that incorporating SNP functional properties, protein-protein interaction networks into GWAS can dissect leading molecular pathways, which cannot be picked up using traditional analyses. We hope to bridge the knowledge gap from sequence to consequence.

scholarly journals Epigenetic Influences on Plant Responses to the Environment [University of Wisconsin - Oshkosh]

2019 ◽  
Author(s):  
Angela L Vickman ◽  
Travis Smith ◽  
Hayley Vandenboom ◽  
Lisa A. Dorn
Keyword(s):  
Gene Expression ◽  
Phenotypic Plasticity ◽  
Molecular Mechanisms ◽  
Molecular Level ◽  
Physical Structure ◽  
Plant Responses ◽  
Appropriate Behavior ◽  
Stressful Environment ◽  
University Of Wisconsin

Plants and animals may respond to changes in the environment at the molecular level by changing the amount of a gene product (a protein) to generate the appropriate behavior or physical structure (a phenotype) for that environment. For example, an extremely stressful environment can cause plants to reproduce immediately rather than waiting for conditions to improve. The molecular mechanisms for changing phenotype with environment (phenotypic plasticity) are not clear, however previous studies have shown plasticity may be the result of failing to change expression to maintain a phenotype or a deliberate change in expression altering the phenotype. To explore the molecular mechanisms underlying phenotypic plasticity, I am using a minION sequencing apparatus to re-sequence three inbred lines of Arabidopsis thaliana with extreme phenotypic plasticity differences and gene expression differences with the environment. I will specifically explore the role of methylated cytosines and adenines in gene expression.

scholarly journals Peptide KRP Conjugated with Doxorubicin Exerts Anti-Tumor Activity by Regulating RPS6KA2 in Osteosarcoma

2021 ◽  
Author(s):  
Mei Yu ◽  
Jiameng Liu ◽  
Zhiyuan Lu ◽  
Yiyang Chen ◽  
Dongjie Zhang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
S6 Kinase ◽  
Protein Protein Interaction ◽  
Qrt Pcr ◽  
Ribosomal Protein S6 ◽  
Ppi Networks ◽  
Specific Tumor ◽  
Network Analyst ◽  
Anti Tumor Activity

Abstract Objectives: Osteosarcoma (OS) is the most common primary solid malignant tumor of the bone in adolescents. Conventional treatment of OS by surgery and chemotherapy is not effective and the prognosis is poor. Our previous study demonstrated that a novel cell-penetrating peptide (KRP) that, coupled to doxorubicin (DOX), allowed specific tumor targeting. However, the underlying molecular mechanisms of the KRP-DOX antitumor effect were not completely elucidated. Therefore, the present work aimed to identify key candidate genes by integrated bioinformatics analysis. Methods: Differentially expressed genes (DEGs) were screened using the Network Analyst. The functions and pathway involvements of the DEGs were analyzed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively. The protein-protein interaction (PPI) network was used to identify hub genes. In addition, quantitative RT-PCR (qRT-PCR) and Western blotting were performed to assess the expression level of candidate biomarkers in OS cells after KRP-DOX treatment. Results: A total of 790 DEGs were identified. GO functional analysis and KEGG pathway analysis demonstrated that the DEGs were mostly enriched in the ribosome. DEGs were visualized by PPI networks. After treatment of OS cells with KRP-DOX, the downregulated ribosomal protein S6 kinase A2 (RPS6KA2) was found to be closely related to inhibition of OS proliferation. In agreement with the bioinformatics analysis, qRT-PCR and western blot results showed low expression of RPS6KA2 in osteosarcoma cells in the KRP-DOX treatment group.Conclusions: RPS6KA2 is significantly associated with the KRP-DOX anti-tumor effect and may serve as a candidate biomarker and therapeutic target for OS.

scholarly journals Endometritis and pyometra in bitches: a review

2013 ◽  
Vol 58 (No. 6) ◽  
pp. 289-297 ◽  
Author(s):  
B. Kempisty ◽  
D. Bukowska ◽  
M. Wozna ◽  
H. Piotrowska ◽  
M. Jackowska ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Reproductive Tract ◽  
Molecular Level ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Clinical Stages ◽  
Compound Process ◽  
Immunological Changes

Endometritis-pyometra is the most frequent and complex pathology in domestic bitches. This process involves several immunological changes as well as molecular mechanisms responsible for inflammation in the female uterus. The various clinical stages of pyometra are associated with various symptoms. In this review, several aspects are described, including physiological and pathological mechanisms as well as molecular changes which take place during induction of endometritis-pyometra. The authors also highlight the important role of growth factors and their receptors in this process. It is well known that pyometra is a compound process which mainly involves immunological changes during inflammation. However, this review presents a new overview of this process, which includes changes at the molecular level, e.g., the altered expression of genes crucial for the development of this disease. Although pyometra is the most frequent disease of the reproductive tract in bitches, the molecular basis of this process is still not entirely understood.  

scholarly journals Chaperones, Canalization, and Evolution of Animal Forms

2018 ◽  
Vol 19 (10) ◽  
pp. 3029 ◽  
Author(s):  
Atsuko Sato
Keyword(s):  
Molecular Mechanisms ◽  
Molecular Level ◽  
Bet Hedging ◽  
Evolutionary Processes ◽  
Expression Levels ◽  
Developmental Biologist ◽  
It Impacts ◽  
Organismal Development ◽  
Developmental Buffering

Over half a century ago, British developmental biologist Conrad Hal Waddington proposed the idea of canalization, that is, homeostasis in development. Since the breakthrough that was made by Rutherford and Lindquist (1998), who proposed a role of Hsp90 in developmental buffering, chaperones have gained much attention in the study of canalization. However, recent studies have revealed that a number of other molecules are also potentially involved in canalization. Here, I introduce the emerging role of DnaJ chaperones in canalization. I also discuss how the expression levels of such buffering molecules can be altered, thereby altering organismal development. Since developmental robustness is maternally inherited in various organisms, I propose that dynamic bet hedging, an increase in within-clutch variation in offspring phenotypes that is caused by unpredictable environmental challenges to the mothers, plays a key role in altering the expression levels of buffering molecules. Investigating dynamic bet hedging at the molecular level and how it impacts upon morphological phenotypes will help our understanding of the molecular mechanisms of canalization and evolutionary processes.

scholarly journals Resilience and evolvability of protein-protein interaction networks

2020 ◽  
Author(s):  
Brennan Klein ◽  
Ludvig Holmér ◽  
Keith M. Smith ◽  
Mackenzie M. Johnson ◽  
Anshuman Swain ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Preferential Attachment ◽  
Network Resilience ◽  
Biological Noise ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
Ppi Networks

AbstractProtein-protein interaction (PPI) networks represent complex intra-cellular protein interactions, and the presence or absence of such interactions can lead to biological changes in an organism. Recent network-based approaches have shown that a phenotype’s PPI network’s resilience to environmental perturbations is related to its placement in the tree of life; though we still do not know how or why certain intra-cellular factors can bring about this resilience. One such factor is gene expression, which controls the simultaneous presence of proteins for allowed extant interactions and the possibility of novel associations. Here, we explore the influence of gene expression and network properties on a PPI network’s resilience, focusing especially on ribosomal proteins—vital molecular-complexes involved in protein synthesis, which have been extensively and reliably mapped in many species. Using publicly-available data of ribosomal PPIs for E. coli, S.cerevisae, and H. sapiens, we compute changes in network resilience as new nodes (proteins) are added to the networks under three node addition mechanisms—random, degree-based, and gene-expression-based attachments. By calculating the resilience of the resulting networks, we estimate the effectiveness of these node addition mechanisms. We demonstrate that adding nodes with gene-expression-based preferential attachment (as opposed to random or degree-based) preserves and can increase the original resilience of PPI network. This holds in all three species regardless of their distributions of gene expressions or their network community structure. These findings introduce a general notion of prospective resilience, which highlights the key role of network structures in understanding the evolvability of phenotypic traits.1Author SummaryProteins in organismal cells are present at different levels of concentration and interact with other proteins to provide specific functional roles. Accumulating lists of all of these interactions, complex networks of protein interactions become apparent. This allows us to begin asking whether there are network-level mechanisms at play guiding the evolution of biological systems. Here, using this network perspective, we address two important themes in evolutionary biology (i) How are biological systems able to successfully incorporate novelty? (ii) What is the evolutionary role of biological noise in evolutionary novelty? We consider novelty to be the introduction of a new protein, represented as a new “node”, into a network. We simulate incorporation of novel proteins into Protein-Protein Interaction (PPI) networks in different ways and analyse how the resilience of the PPI network alters. We find that novel interactions guided by gene expression (indicative of concentration levels of proteins) creates a more resilient network than either uniformly random interactions or interactions guided solely by the network structure (preferential attachment). Moreover, simulated biological noise in the gene expression increases network resilience. We suggest that biological noise induces novel structure in the PPI network which has the effect of making it more resilient.

scholarly journals Identification of key candidate genes and pathways in axial Spondyloarthritis through integrated bioinformatics analysis

2020 ◽  
Author(s):  
Zhen-zhen Zhang ◽  
Jing Zeng ◽  
Hai-hong Li ◽  
Yu-cong Zou ◽  
Shuang Liang ◽  
...  
Keyword(s):  
Immunohistochemical Staining ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Axial Spondyloarthritis ◽  
Kegg Pathway ◽  
Transcriptional Regulatory Network ◽  
Rt Pcr ◽  
Protein Protein Interaction ◽  
Ppi Networks ◽  
Pathway Analyses

AbstractBackgroundRadiographic axial Spondyloarthritis (r-axSpA) is the prototypic form of seronegative spondyloarthritis (SpA). In the present study, we evaluated the key genes related with r-axSpA, and then elucidated the possible molecular mechanisms of r-axSpA.Material/MethodsThe gene expression GSE13782 was downloaded from the GEO database contained five proteoglycan-induced spondylitis mice and three naïve controls. The differentially expressed genes (DEGs) were identified with the Bioconductor affy package in R. Gene Ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were built with the DAVID program followed by construction of a protein-protein interaction (PPI) network performed with Cytoscape. WebGestalt was performed to construct transcriptional regulatory network and microRNAs-target regulatory networks. RT-PCR and immunohistochemical staining were performed to testify the expression of hub genes, transcription factors (TFs) and microRNAs.ResultsA total of 230 DEGs were identified. PPI networks were constructed by mapping DEGs into STRING, in which 20 hub proteins were identified. KEGG pathway analyses revealed that the chemokine, NOD-like receptor, IL-17, and TNF signalling pathways were altered. GO analyses revealed that DEGs were extensively involved in the regulation of cytokine production, the immune response, the external side of the plasma membrane, and G-protein coupled chemoattractant receptor activity. The results of RT-PCR and immunohistochemical staining demonstrated that the expression of DEGs, TFs and microRNAs in our experiment were basically consistent with the predictions.ConclusionsThe results of this study offer insight into the pathomechanisms of r-axSpA and provide potential research directions.

Molecular and Immunological Mechanisms Underlying the Various Pharmacological Properties of the Potent Bioflavonoid, Rutin

2020 ◽  
Vol 20 (10) ◽  
pp. 1590-1596
Author(s):  
David O.C. Yong ◽  
Sanggetha R. Saker ◽  
Dinesh K. Chellappan ◽  
Thiagarajan Madheswaran ◽  
Jithendra Panneerselvam ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Molecular Level ◽  
Signalling Pathways ◽  
Ancient History ◽  
Pharmacological Activities ◽  
Herbal Products ◽  
Therapeutic Benefits ◽  
Immunological Mechanisms ◽  
Therapeutic Properties

The application of medicinal plants has captured the interest of researchers in recent times due to their potent therapeutic properties and a better safety profile. The prominent role of herbal products in treating and preventing multiple diseases dates back to ancient history and most of the modern drugs today originated from their significant sources owing to their ability to control multiple targets via different signalling pathways. Among them, flavonoids consist of a large group of polyphenols, which are well known for their various therapeutic benefits. Rutin is considered one of the attractive phytochemicals and important flavonoids in the pharmaceutical industry due to its diverse pharmacological activities via various underlying molecular mechanisms. It is usually prescribed for various disease conditions such as varicosities, haemorrhoids and internal haemorrhage. In this review, we have discussed and highlighted the different molecular mechanisms attributed to the various pharmacological activities of rutin, such as antioxidant, anti-inflammatory, anticancer, anti-allergic and antidiabetic. This review will be beneficial to herbal, biological and molecular scientists in understanding the pharmacological relevance of rutin at the molecular level.

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