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CNS Spectrums Apr 2022Blood platelets, due to shared biochemical and functional properties with presynaptic serotonergic neurons, constituted, over the years, an attractive peripheral... (Review)
Review
BACKGROUND
Blood platelets, due to shared biochemical and functional properties with presynaptic serotonergic neurons, constituted, over the years, an attractive peripheral biomarker of neuronal activity. Therefore, the literature strongly focused on the investigation of eventual structural and functional platelet abnormalities in neuropsychiatric disorders, particularly in depressive disorder. Given their impact in biological psychiatry, the goal of the present paper was to review and critically analyze studies exploring platelet activity, functionality, and morpho-structure in subjects with depressive disorder.
METHODS
According to the PRISMA guidelines, we performed a systematic review through the PubMed database up to March 2020 with the search terms: (1) platelets in depression [Title/Abstract]"; (2) "(platelets[Title]) AND depressive disorder[Title/Abstract]"; (3) "(Platelet[Title]) AND major depressive disorder[Title]"; (4) (platelets[Title]) AND depressed[Title]"; (5) (platelets[Title]) AND depressive episode[Title]"; (6) (platelets[Title]) AND major depression[Title]"; (7) platelet activation in depression[All fields]"; and (8) platelet reactivity in depression[All fields]."
RESULTS
After a detailed screening analysis and the application of specific selection criteria, we included in our review a total of 106 for qualitative synthesis. The studies were classified into various subparagraphs according to platelet characteristics analyzed: serotonergic system (5-HT2A receptors, SERT activity, and 5-HT content), adrenergic system, MAO activity, biomarkers of activation, responsivity, morphological changes, and other molecular pathways.
CONCLUSIONS
Despite the large amount of the literature examined, nonunivocal and, occasionally, conflicting results emerged. However, the findings on structural and metabolic alterations, modifications in the expression of specific proteins, changes in the aggregability, or in the responsivity to different pro-activating stimuli, may be suggestive of potential platelet dysfunctions in depressed subjects, which would result in a kind of hyperreactive state. This condition could potentially lead to an increased cardiovascular risk. In line with this hypothesis, we speculated that antidepressant treatments would seem to reduce this hyperreactivity while representing a potential tool for reducing cardiovascular risk in depressed patients and, maybe, in other neuropsychiatric conditions. However, the problem of the specificity of platelet biomarkers is still at issue and would deserve to be deepened in future studies.
Topics: Antidepressive Agents; Biomarkers; Blood Platelets; Depressive Disorder, Major; Humans; Serotonin
PubMed: 33092669
DOI: 10.1017/S1092852920001959 -
Journal of Dental Sciences Jan 2022Nasal obstruction leads to oral breathing and consequently hypoxia. The purpose of this study was to determine the influence of hypoxia on inflammatory response and the...
BACKGROUND/PURPOSE
Nasal obstruction leads to oral breathing and consequently hypoxia. The purpose of this study was to determine the influence of hypoxia on inflammatory response and the effect on alveolar bone development in a rat model in which mouth breathing was induced by nasal obstruction.
MATERIALS AND METHODS
Unilateral nasal obstruction was performed by injecting a Merocel sponge into the nasal cavity of 8-week-old Sprague Dawley (SD) rats. After 3 and 6 weeks of nasal obstruction, rats were sacrificed, the organs were weighed, and the changes in mandibular bone quality were examined by micro-computed tomography (μ-CT). The stereomicroscope was used for the morphological analysis of alveolar bone loss in response to nasal obstruction. Hematoxylin and Eosin (H&E) and immunohistochemical staining were employed to examine inflammation and bone remodeling induced by hypoxia.
RESULTS
Nasal obstruction led to a delay in overall growth and organ development. The bone mineral density (BMD) and bone volume/total volume (BV/TV) of the mandible were reduced due to nasal obstruction, and the loss of the alveolar bone was confirmed morphologically. Our nasal obstruction method was observed to be successful in inducing hypoxia along with an increase in hypoxia-inducible factor 1-alpha (HIF-α). Oral hypoxia induced by nasal obstruction increased inflammatory response, and increased expression of receptor activator of nuclear factor kappa-Β ligand (RANKL) led to bone destruction.
CONCLUSION
This study demonstrated that nasal obstruction induced mouth breathing led to hypoxia in a rat model. Under hypoxic conditions, an increase in osteoclast differentiation induced by activation of the inflammatory pathway causes destructive changes in the alveolar bone.
PubMed: 35028036
DOI: 10.1016/j.jds.2021.05.012 -
Polymers Feb 2021Three-dimensional (3D) printing is a valuable tool in the production of complexes structures with specific shapes for tissue engineering. Differently from native... (Review)
Review
Three-dimensional (3D) printing is a valuable tool in the production of complexes structures with specific shapes for tissue engineering. Differently from native tissues, the printed structures are static and do not transform their shape in response to different environment changes. Stimuli-responsive biocompatible materials have emerged in the biomedical field due to the ability of responding to other stimuli (physical, chemical, and/or biological), resulting in microstructures modifications. Four-dimensional (4D) printing arises as a new technology that implements dynamic improvements in printed structures using smart materials (stimuli-responsive materials) and/or cells. These dynamic scaffolds enable engineered tissues to undergo morphological changes in a pre-planned way. Stimuli-responsive polymeric hydrogels are the most promising material for 4D bio-fabrication because they produce a biocompatible and bioresorbable 3D shape environment similar to the extracellular matrix and allow deposition of cells on the scaffold surface as well as in the inside. Subsequently, this review presents different bioresorbable advanced polymers and discusses its use in 4D printing for tissue engineering applications.
PubMed: 33668617
DOI: 10.3390/polym13040563 -
ACS Nano May 2023Hypoxic pulmonary hypertension (HPH) is characterized by pulmonary vascular sustained constriction and progressive remodeling, which are initiated by hypoxia then with...
Hypoxic pulmonary hypertension (HPH) is characterized by pulmonary vascular sustained constriction and progressive remodeling, which are initiated by hypoxia then with hypoxia-induced additive factors including pulmonary vascular endothelium injury, intrapulmonary angiotension system imbalance, and inflammation. Now HPH is still an intractable disease lacking effective treatments. Gene therapy has a massive potential for HPH but is hindered by a lack of efficient targeted delivery and hypoxia-responsive regulation systems for transgenes. Herein, we constructed the hypoxia-responsive plasmid of angiotensin-converting enzyme 2 (ACE2) with endothelial-specific promoter Tie2 and a hypoxia response element and next prepared its biomimetic nanoparticle delivery system, named ACE2-CS-PRT@PM, by encapsulating the plasmid of ACE2 with protamine and chondroitin sulfate as the core then coated it with a platelet membrane as a shell for targeting the injured pulmonary vascular endothelium. ACE2-CS-PRT@PM has a 194.3 nm diameter with a platelet membrane-coating core-shell structure and a negatively charged surface, and it exhibits higher delivery efficiency targeting to pulmonary vascular endothelium and hypoxia-responsive overexpression of ACE2 in endothelial cells in a hypoxia environment. In vitro, ACE2-CS-PRT@PM significantly inhibited the hypoxia-induced proliferation of pulmonary smooth muscle cells. In vivo, ACE2-CS-PRT@PM potently ameliorated the hemodynamic dysfunction and morphological abnormality and largely reversed HPH via inhibiting the hypoxic proliferation of pulmonary artery smooth muscle cells, reducing pulmonary vascular remodeling, restoring balance to the intrapulmonary angiotension system, and improving the inflammatory microenvironment without any detectable toxicity. Therefore, ACE2-CS-PRT@PM is promising for the targeted gene therapy of HPH.
Topics: Humans; Hypertension, Pulmonary; Angiotensin-Converting Enzyme 2; Endothelial Cells; Biomimetics; Hypoxia; Cell Proliferation
PubMed: 37071566
DOI: 10.1021/acsnano.2c12190 -
Journal of Clinical and Translational... Nov 2020Early identification of patients who fail to lung stereotactic body radiation therapy (SBRT) is vital as they can benefit from salvage therapy. Main guidelines recommend... (Review)
Review
BACKGROUND
Early identification of patients who fail to lung stereotactic body radiation therapy (SBRT) is vital as they can benefit from salvage therapy. Main guidelines recommend computed tomography (CT) to assess response and use of 18F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET)/CT only when a local recurrence is suspected in CT. The pattern of radiation-induced lung injury caused by SBRT is different from changes seen after conventional radiation therapy in terms of extent, time of manifestation, and morphologic characteristics, and knowing this is crucial for proper monitoring of the tumor response. In certain cases, it may be difficult to differentiate response from progression or recurrence on CT and, in addition, some changes in CT take a long time to evolve before they are considered suspicious, making early diagnosis difficult. Metabolic changes often precede morphological changes, so F-FDG PET/CT quantitative and qualitative metabolic criteria can be useful in assessing early response and detecting relapses. However, the optimal practice for follow-up remains unclear and there is an active search for imaging markers for recurrent disease, including CT texture analysis, biomarker assays, new PET/CT isotopes, and magnetic resonance imaging.
AIM
The aim of the study was to review the radiological changes that are objectified after pulmonary SBRT and the metabolic changes in F-FDG PET/CT, to assess the usefulness of following up patients with F-FDG PET/CT.
RELEVANCE FOR PATIENTS
At present, the evaluation of response and diagnosis of relapse after SBRT are difficult and the incorporation of routine F-FDG PET/CT may have value in early diagnosis of relapse when the patient may still benefit from rescue treatment.
PubMed: 33501386
DOI: No ID Found -
Angewandte Chemie (International Ed. in... Aug 2023Mechanochemical approaches are widely used for the efficient, solvent-free synthesis of organic molecules, however their applicability to the synthesis of functional...
Mechanochemical approaches are widely used for the efficient, solvent-free synthesis of organic molecules, however their applicability to the synthesis of functional polymers has remained underexplored. Herein, we demonstrate for the first time that mechanochemically triggered free-radical polymerization allows solvent- and initiator-free syntheses of structurally and morphologically well-defined complex functional macromolecular architectures, namely stimuliresponsive microgels. The developed mechanochemical polymerization approach is applicable to a variety of monomers and allows synthesizing microgels with tunable chemical structure, variable size, controlled number of crosslinks and reactive functional end-groups.
PubMed: 37177824
DOI: 10.1002/anie.202305783 -
Glia May 2021Astrocytes fulfil many functions in the central nervous system (CNS), including contribution to the blood brain barrier, synapse formation, and trophic support. In...
Astrocytes fulfil many functions in the central nervous system (CNS), including contribution to the blood brain barrier, synapse formation, and trophic support. In addition, they can mount an inflammatory response and are heterogeneous in morphology and function. To extensively characterize astrocyte subtypes, we FACS-isolated and gene expression profiled distinct astrocyte subtypes from three central nervous system regions; forebrain, hindbrain and spinal cord. Astrocyte subpopulations were separated based on GLAST/SLC1A3 and ACSA-2/ATP1B2 cell surface expression. The local brain environment proved key in establishing different transcriptional programs in astrocyte subtypes. Transcriptional differences between subtypes were also apparent in experimental autoimmune encephalomyelitis (EAE) mice, where these astrocyte subtypes showed distinct responses. While gene expression signatures associated with blood-brain barrier maintenance were lost, signatures involved in neuroinflammation and neurotoxicity were increased in spinal cord astrocytes, especially during acute disease stages. In chronic stages of EAE, this reactive astrocyte signature was slightly decreased, while obtaining a more proliferative profile, which might be relevant for glia scar formation and tissue regeneration. Morphological heterogeneity of astrocytes previously indicated the presence of astrocyte subtypes, and here we show diversity based on transcriptome variation associated with brain regions and differential responsiveness to a neuroinflammatory insult (EAE).
Topics: Adenosine Triphosphatases; Animals; Astrocytes; Cation Transport Proteins; Cell Adhesion Molecules, Neuronal; Encephalomyelitis, Autoimmune, Experimental; Mice; Mice, Inbred C57BL; Neuroinflammatory Diseases; Spinal Cord
PubMed: 33332631
DOI: 10.1002/glia.23954 -
International Journal of Molecular... Dec 2022Salt stress is an unfavorable outcome of global climate change, adversely affecting crop growth and yield. It is the second-biggest abiotic factor damaging the... (Review)
Review
Salt stress is an unfavorable outcome of global climate change, adversely affecting crop growth and yield. It is the second-biggest abiotic factor damaging the morphological, physio-biochemical, and molecular processes during seed germination and plant development. Salt responses include modulation of hormonal biosynthesis, ionic homeostasis, the antioxidant defense system, and osmoprotectants to mitigate salt stress. Plants trigger salt-responsive genes, proteins, and metabolites to cope with the damaging effects of a high salt concentration. Enhancing salt tolerance among crop plants is direly needed for sustainable global agriculture. Novel protein markers, which are used for crop improvement against salt stress, are identified using proteomic techniques. As compared to single-technique approaches, the integration of genomic tools and exogenously applied chemicals offers great potential in addressing salt-stress-induced challenges. The interplay of salt-responsive proteins and genes is the missing key of salt tolerance. The development of salt-tolerant crop varieties can be achieved by integrated approaches encompassing proteomics, metabolomics, genomics, and genome-editing tools. In this review, the current information about the morphological, physiological, and molecular mechanisms of salt response/tolerance in crops is summarized. The significance of proteomic approaches to improve salt tolerance in various crops is highlighted, and an integrated omics approach to achieve global food security is discussed. Novel proteins that respond to salt stress are potential candidates for future breeding of salt tolerance.
Topics: Proteomics; Plant Breeding; Crops, Agricultural; Genomics; Salt Tolerance; Stress, Physiological
PubMed: 36613963
DOI: 10.3390/ijms24010518 -
Frontiers in Immunology 2022Eosinophils are hallmarks in allergic type 2 inflammation and are known to release cytotoxic granule proteins that contribute to inflammation. Eosinophils develop in the...
OBJECTIVE
Eosinophils are hallmarks in allergic type 2 inflammation and are known to release cytotoxic granule proteins that contribute to inflammation. Eosinophils develop in the bone marrow from hematopoietic stem cells and once mature, have a limited lifespan in culture, making them difficult to study . IL-33 has increasingly been shown as a key regulator of type 2 inflammation signaling through its receptor, ST2. The present study was conducted to detail a method of eosinophil differentiation from hematopoietic stem cells and determine the response to IL-33.
METHODS
CD34+ and CD14+ cells were isolated from donor apheresis cones and differentiated into eosinophils or macrophage controls, respectively. Morphologic, transcriptional and protein analyses were performed to validate this method of eosinophil differentiation. The effect of IL-33 on differentiated eosinophils was assessed using qPCR, immunofluorescence, and multiplex cytokine array.
RESULTS
CD34 differentiated eosinophils appear morphologically similar by H&E and express eosinophil peroxidase (EPX) protein as well as the conventional eosinophil transcripts , , and . In addition, differentiated eosinophils expressed both isoforms of the IL-33 receptor, and s throughout the differentiation process. Transcript levels of both IL-33 receptors were up-regulated by treatment with IL-33 at earlier timepoints in the differentiation. These cells also expressed and mRNA which were up-regulated by IL-33 as well. Notably, expression was significantly higher with IL-33 treatment compared to media control at every timepoint measured. IL-33 significantly increased cellular secretion of IL-13 protein at most timepoints throughout differentiation. IL-8, LIF, CCL1, CCL5, CCL7, and CCL8 were also significantly secreted after IL-33 stimulation.
CONCLUSIONS
Our findings suggest that CD34 differentiated eosinophils are morphologically and phenotypically similar to peripheral eosinophils. The release of specific cytokines in direct response to IL-33 may contribute to the pathogenesis of type 2 inflammation and facilitates new avenues for studying eosinophils as effector cells .
Topics: Antigens, CD34; Cytokines; Eosinophil Peroxidase; Eosinophils; Humans; Inflammation; Interleukin-1 Receptor-Like 1 Protein; Interleukin-13; Interleukin-33; Interleukin-4; Interleukin-8; RNA, Messenger
PubMed: 36177009
DOI: 10.3389/fimmu.2022.946643 -
Frontiers in Oncology 2021Metastatic tumor deposits in bone marrow elicit differential bone responses that vary with the type of malignancy. This results in either sclerotic, lytic, or mixed bone... (Review)
Review
Metastatic tumor deposits in bone marrow elicit differential bone responses that vary with the type of malignancy. This results in either sclerotic, lytic, or mixed bone lesions, which can change in morphology due to treatment effects and/or secondary bone remodeling. Hence, morphological imaging is regarded unsuitable for response assessment of bone metastases and in the current Response Evaluation Criteria In Solid Tumors 1.1 (RECIST1.1) guideline bone metastases are deemed unmeasurable. Nevertheless, the advent of functional and molecular imaging modalities such as whole-body magnetic resonance imaging (WB-MRI) and positron emission tomography (PET) has improved the ability for follow-up of bone metastases, regardless of their morphology. Both these modalities not only have improved sensitivity for visual detection of bone lesions, but also allow for objective measurements of bone lesion characteristics. WB-MRI provides a global assessment of skeletal metastases and for a one-step "all-organ" approach of metastatic disease. Novel MRI techniques include diffusion-weighted imaging (DWI) targeting highly cellular lesions, dynamic contrast-enhanced MRI (DCE-MRI) for quantitative assessment of bone lesion vascularization, and multiparametric MRI (mpMRI) combining anatomical and functional sequences. Recommendations for a homogenization of MRI image acquisitions and generalizable response criteria have been developed. For PET, many metabolic and molecular radiotracers are available, some targeting tumor characteristics not confined to cancer type (e.g. F-FDG) while other targeted radiotracers target specific molecular characteristics, such as prostate specific membrane antigen (PSMA) ligands for prostate cancer. Supporting data on quantitative PET analysis regarding repeatability, reproducibility, and harmonization of PET/CT system performance is available. Bone metastases detected on PET and MRI can be quantitatively assessed using validated methodologies, both on a whole-body and individual lesion basis. Both have the advantage of covering not only bone lesions but visceral and nodal lesions as well. Hybrid imaging, combining PET with MRI, may provide complementary parameters on the morphologic, functional, metabolic and molecular level of bone metastases in one examination. For clinical implementation of measuring bone metastases in response assessment using WB-MRI and PET, current RECIST1.1 guidelines need to be adapted. This review summarizes available data and insights into imaging of bone metastases using MRI and PET.
PubMed: 34869009
DOI: 10.3389/fonc.2021.772530