scholarly journals Involvement of cyclooxygenase-2 and prostaglandins in the molecular pathogenesis of inflammatory lung diseases

2006 ◽  
Vol 290 (5) ◽  
pp. L797-L805 ◽  
Author(s):  
Gye Young Park ◽  
John W. Christman
Keyword(s):  
Lung Diseases ◽  
Cell Types ◽  
Therapeutic Interventions ◽  
Biological Research ◽  
Specific Cell ◽  
Exact Nature ◽  
Proinflammatory Response ◽  
Disease States ◽  
Inflammatory Models ◽  
Cox 2

Inducible cyclooxygenase (COX-2) and its metabolites have diverse and potent biological actions that are important for both physiological and disease states of lung. The wide variety of prostaglandin (PG) products are influenced by the level of cellular activation, the exact nature of the stimulus, and the specific cell type involved in their production. In turn, the anti- and proinflammatory response of PG is mediated by a blend of specific surface and intracellular receptors that mediate diverse cellular events. The complexity of this system is being at least partially resolved by the generation of specific molecular biological research tools that include cloning and characterization of the enzymes distal to COX-2 and the corresponding receptors to the final cellular products of arachidonic metabolism. The most informative of these approaches have employed genetically modified animals and specific receptor antagonists to determine the exact role of specific COX-2-derived metabolites on specific cell types of the lung in the context of inflammatory models. These data have suggested a number of cell-specific, pathway-specific, and receptor-specific approaches that could lead to effective therapeutic interventions for most inflammatory lung diseases.

Epithelial Organotypic Cultures: A Viable Model to Address Mechanisms of Carcinogenesis by Epitheliotropic Viruses

2018 ◽  
Vol 18 (4) ◽  
pp. 246-255 ◽  
Author(s):  
Lara Termini ◽  
Enrique Boccardo
Keyword(s):  
Three Dimensional ◽  
Cell Types ◽  
Experimental Models ◽  
Biological Research ◽  
Specific Gene ◽  
Specific Cell ◽  
Organotypic Cultures ◽  
Skin Physiology

In vitro culture of primary or established cell lines is one of the leading techniques in many areas of basic biological research. The use of pure or highly enriched cultures of specific cell types obtained from different tissues and genetics backgrounds has greatly contributed to our current understanding of normal and pathological cellular processes. Cells in culture are easily propagated generating an almost endless source of material for experimentation. Besides, they can be manipulated to achieve gene silencing, gene overexpression and genome editing turning possible the dissection of specific gene functions and signaling pathways. However, monolayer and suspension cultures of cells do not reproduce the cell type diversity, cell-cell contacts, cell-matrix interactions and differentiation pathways typical of the three-dimensional environment of tissues and organs from where they were originated. Therefore, different experimental animal models have been developed and applied to address these and other complex issues in vivo. However, these systems are costly and time consuming. Most importantly the use of animals in scientific research poses moral and ethical concerns facing a steadily increasing opposition from different sectors of the society. Therefore, there is an urgent need for the development of alternative in vitro experimental models that accurately reproduce the events observed in vivo to reduce the use of animals. Organotypic cultures combine the flexibility of traditional culture systems with the possibility of culturing different cell types in a 3D environment that reproduces both the structure and the physiology of the parental organ. Here we present a summarized description of the use of epithelial organotypic for the study of skin physiology, human papillomavirus biology and associated tumorigenesis.

scholarly journals Deep Learning Identifies Cardiomyocyte Nuclei in Murine Tissue with High Precision

2020 ◽  
Author(s):  
Shah R. Ali ◽  
Dan Nguyen ◽  
Brandon Wang ◽  
Steven Jiang ◽  
Hesham A. Sadek
Keyword(s):  
Deep Learning ◽  
Cell Types ◽  
Label Cell ◽  
Biological Research ◽  
Mouse Heart ◽  
Specific Cell ◽  
Label Free ◽  
Structural Protein ◽  
Mammalian Tissues ◽  
Murine Tissue

ABSTRACTProper identification and annotation of cells in mammalian tissues is of paramount importance to biological research. Various approaches are currently used to identify and label cell types of interest in complex tissues. In this report, we generated an artificial intelligence (AI) deep learning model that uses image segmentation to predict cardiomyocyte nuclei in mouse heart sections without a specific cardiomyocyte nuclear label. This tool can annotate cardiomyocytes highly sensitively and specifically (AUC 0.94) using only cardiomyocyte structural protein immunostaining and a global nuclear stain. We speculate that our method is generalizable to other tissues to annotate specific cell types and organelles in a label-free way.

scholarly journals A single-cell and spatial atlas of autopsy tissues reveals pathology and cellular targets of SARS-CoV-2

2021 ◽  
Author(s):  
Toni M. Delorey ◽  
Carly G. K. Ziegler ◽  
Graham Heimberg ◽  
Rachelly Normand ◽  
Yiming Yang ◽  
...  
Keyword(s):  
Single Cell ◽  
Lung Tissue ◽  
Tissue Bank ◽  
Cell Types ◽  
H1n1 Influenza ◽  
Lung Epithelial Cells ◽  
Therapeutic Interventions ◽  
Alveolar Type ◽  
Specific Cell ◽  
Phagocytic Cells

AbstractThe SARS-CoV-2 pandemic has caused over 1 million deaths globally, mostly due to acute lung injury and acute respiratory distress syndrome, or direct complications resulting in multiple-organ failures. Little is known about the host tissue immune and cellular responses associated with COVID-19 infection, symptoms, and lethality. To address this, we collected tissues from 11 organs during the clinical autopsy of 17 individuals who succumbed to COVID-19, resulting in a tissue bank of approximately 420 specimens. We generated comprehensive cellular maps capturing COVID-19 biology related to patients’ demise through single-cell and single-nucleus RNA-Seq of lung, kidney, liver and heart tissues, and further contextualized our findings through spatial RNA profiling of distinct lung regions. We developed a computational framework that incorporates removal of ambient RNA and automated cell type annotation to facilitate comparison with other healthy and diseased tissue atlases. In the lung, we uncovered significantly altered transcriptional programs within the epithelial, immune, and stromal compartments and cell intrinsic changes in multiple cell types relative to lung tissue from healthy controls. We observed evidence of: alveolar type 2 (AT2) differentiation replacing depleted alveolar type 1 (AT1) lung epithelial cells, as previously seen in fibrosis; a concomitant increase in myofibroblasts reflective of defective tissue repair; and, putative TP63+ intrapulmonary basal-like progenitor (IPBLP) cells, similar to cells identified in H1N1 influenza, that may serve as an emergency cellular reserve for severely damaged alveoli. Together, these findings suggest the activation and failure of multiple avenues for regeneration of the epithelium in these terminal lungs. SARS-CoV-2 RNA reads were enriched in lung mononuclear phagocytic cells and endothelial cells, and these cells expressed distinct host response transcriptional programs. We corroborated the compositional and transcriptional changes in lung tissue through spatial analysis of RNA profiles in situ and distinguished unique tissue host responses between regions with and without viral RNA, and in COVID-19 donor tissues relative to healthy lung. Finally, we analyzed genetic regions implicated in COVID-19 GWAS with transcriptomic data to implicate specific cell types and genes associated with disease severity. Overall, our COVID-19 cell atlas is a foundational dataset to better understand the biological impact of SARS-CoV-2 infection across the human body and empowers the identification of new therapeutic interventions and prevention strategies.

Polymeric Vectors for Strategic Delivery of Nucleic Acids

Nano LIFE ◽  
2017 ◽  
Vol 07 (02) ◽  
pp. 1730003
Author(s):  
Andrew Dunn ◽  
Donglu Shi
Keyword(s):  
Molecular Weight ◽  
Transfection Efficiency ◽  
Cell Types ◽  
Primary Amines ◽  
Biological Research ◽  
Specific Cell ◽  
Nucleic Acid Delivery ◽  
Biological Studies

Genomic modification through nucleic acid delivery is a frequently applied method in fundamental biological studies and offers a potent therapeutic strategy for disease treatment and biological research. Delivery of nucleic sequences is therefore an attractive facet of biological nanotechnology as highly specific, efficient, and nonantagonistic delivery is necessary for in vivo and clinical use. Previous vectors have suffered from immunogenic responses, serum dependent inactivation, and cytotoxicity, hindering their translational applicability. Current research in polymeric-based nucleotide delivery strives to offer a highly biocompatible, broad use vector through the utilization of polypeptide and polyamine conjugation that can be easily tailored for specific targeting or wide dissemination. Cross-linking low molecular weight polyamines and lipophilic derivatization for amphiphile creation has lead to improved biocompatibility and transfection efficiency compared to higher molecular weight polyamines. Derivatization of hyperbranched and dendritic polyamido- and polyamines has allowed for the formation of efficient in vivo transfection vectors; ring opening synthesis of N-carboxyanhydride amino acids have led to controlled peptide architectures for improved transfection while simultaneously providing convenient primary amines useful in functionalization. Polymer libraries of poly(ß-amino esters) have provided insights into useful architectures for in vitro and in vivo gene delivery. Grafting small molecules to polyamines, such as folate and galactose, for enhanced interaction with cell surface receptors for selective targeting of specific cell types has proven to be encouraging and remains a prominent aspect in biological nanotechnology.

scholarly journals A pharmacological interactome platform for discovery of pain mechanisms and targets

2020 ◽  
Author(s):  
Andi Wangzhou ◽  
Candler Paige ◽  
Sanjay V Neerukonda ◽  
Gregory Dussor ◽  
Pradipta R Ray ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Sensory Neurons ◽  
Cell Types ◽  
Specific Cell ◽  
Interaction Point ◽  
Pain Mechanisms ◽  
Peripheral Cell ◽  
Disease States ◽  
Enteric Glial Cells ◽  
Receptor Interactions

AbstractCells communicate with each other through ligand and receptor interactions. In the case of the peripheral nervous system, these ligand-receptor interactions shape sensory experience. In disease states, such as chronic pain, these ligand-receptor interactions can change the excitability of target neurons augmenting nociceptive input to the CNS. While the importance of these cell to neuron interactions are widely acknowledged, they have not been thoroughly characterized. We sought to address this by cataloging how peripheral cell types interact with sensory neurons in the dorsal root ganglion (DRG) using RNA sequencing datasets. Using single cell sequencing datasets from mouse we created a comprehensive interactome map for how mammalian sensory neurons interact with 42 peripheral cell types. We used this knowledge base to understand how specific cell types and sensory neurons interact in disease states. In mouse datasets, we created an interactome of colonic enteric glial cells in the naïve and inflamed state with sensory neurons that specifically innervate this tissue. In human datasets, we created interactomes of knee joint macrophages from rheumatoid arthritis patients and pancreatic cancer samples with human DRG. Collectively, these interactomes highlight ligand-receptor interactions in mouse models and human disease states that reflect the complexity of cell to neuron signaling in chronic pain states. These interactomes also highlight therapeutic targets, such as the epidermal growth factor receptor (EGFR), which was a common interaction point emerging from our studies.

scholarly journals Regulation of Transcription Factor NF-κB in Its Natural Habitat: The Nucleus

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 753
Author(s):  
Susanne Bacher ◽  
Johanna Meier-Soelch ◽  
Michael Kracht ◽  
M. Lienhard Schmitz
Keyword(s):  
Transcription Factor ◽  
Target Genes ◽  
Natural Habitat ◽  
Transcriptional Response ◽  
Gene Clusters ◽  
Cell Types ◽  
Therapeutic Interventions ◽  
Specific Cell ◽  
Regulation Of Transcription ◽  
Specific Regulation

Activation of the transcription factor NF-κB elicits an individually tailored transcriptional response in order to meet the particular requirements of specific cell types, tissues, or organs. Control of the induction kinetics, amplitude, and termination of gene expression involves multiple layers of NF-κB regulation in the nucleus. Here we discuss some recent advances in our understanding of the mutual relations between NF-κB and chromatin regulators also in the context of different levels of genome organization. Changes in the 3D folding of the genome, as they occur during senescence or in cancer cells, can causally contribute to sustained increases in NF-κB activity. We also highlight the participation of NF-κB in the formation of hierarchically organized super enhancers, which enable the coordinated expression of co-regulated sets of NF-κB target genes. The identification of mechanisms allowing the specific regulation of NF-κB target gene clusters could potentially enable targeted therapeutic interventions, allowing selective interference with subsets of the NF-κB response without a complete inactivation of this key signaling system.

Correlative transmission and high-resolution scanning electron microscopic studies on pituitary cells

1990 ◽  
Vol 48 (3) ◽  
pp. 20-21
Author(s):  
S. Tai
Keyword(s):  
Cell Types ◽  
Depth Of Field ◽  
Secretory Cells ◽  
Specific Cell ◽  
Pituitary Cells ◽  
Electron Microscopic ◽  
3 Dimensional ◽  
Microscopic Studies ◽  
Structure And Activity ◽  
Intracellular Structure

Extensive cytological and histological research, correlated with physiological experimental analysis, have been done on the anterior pituitaries of many different vertebrates which have provided the knowledge to create the concept that specific cell types synthesize, store and release their specific hormones. These hormones are stored in or associated with granules. Nevertheless, there are still many doubts - that need further studies, specially on the ultrastructure and physiology of these endocrine cells during the process of synthesis, transport and secretion, whereas some new methods may provide the information about the intracellular structure and activity in detail.In the present work, ultrastructural study of the hormone-secretory cells of chicken pituitaries have been done by using TEM as well as HR-SEM, to correlate the informations obtained from 2-dimensional TEM micrography with the 3-dimensional SEM topographic images, which have a continous surface with larger depth of field that - offers the adventage to interpretate some intracellular structures which were not possible to see using TEM.

Nanotheranostic agents for neurodegenerative diseases

2020 ◽  
Vol 4 (6) ◽  
pp. 645-675
Author(s):  
Parasuraman Padmanabhan ◽  
Mathangi Palanivel ◽  
Ajay Kumar ◽  
Domokos Máthé ◽  
George K. Radda ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Neurodegenerative Diseases ◽  
Cell Types ◽  
Specific Cell ◽  
Ageing Population ◽  
Target Tissue ◽  
Therapeutic Approaches ◽  
Surface Receptors ◽  
Theranostic Agents ◽  
Preclinical Animal Models

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.

scholarly journals Unique Aspects of the Developing Lung Circulation: Structural Development and Regulation of Vasomotor Tone

2016 ◽  
Vol 6 (4) ◽  
pp. 407-425 ◽  
Author(s):  
Yuangsheng Gao ◽  
David N. Cornfield ◽  
Kurt R. Stenmark ◽  
Bernard Thébaud ◽  
Steven H. Abman ◽  
...  
Keyword(s):  
Lung Development ◽  
Lung Diseases ◽  
Vascular Tone ◽  
Current Knowledge ◽  
Normal Lung ◽  
Pulmonary Vasculature ◽  
Structural Development ◽  
Vasomotor Tone ◽  
Disease States ◽  
Vasculogenesis And Angiogenesis

This review summarizes our current knowledge on lung vasculogenesis and angiogenesis during normal lung development and the regulation of fetal and postnatal pulmonary vascular tone. In comparison to that of the adult, the pulmonary circulation of the fetus and newborn displays many unique characteristics. Moreover, altered development of pulmonary vasculature plays a more prominent role in compromised pulmonary vasoreactivity than in the adult. Clinically, a better understanding of the developmental changes in pulmonary vasculature and vasomotor tone and the mechanisms that are disrupted in disease states can lead to the development of new therapies for lung diseases characterized by impaired alveolar structure and pulmonary hypertension.

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