-
Archivum Immunologiae Et Therapiae... Jan 2024Venous thromboembolism, encompassing acute pulmonary embolism (APE) and deep vein thrombosis (DVT), is a potentially fatal disease with complex pathophysiology.... (Review)
Review
Venous thromboembolism, encompassing acute pulmonary embolism (APE) and deep vein thrombosis (DVT), is a potentially fatal disease with complex pathophysiology. Traditionally, the Virchow triad provided a framework for understanding the pathogenic contributors to thrombus formation, which include endothelial dysfunction, alterations in blood flow and blood hypercoagulability. In the last years, it has become apparent that immunity plays a central role in thrombosis, interacting with classical prothrombotic mechanisms, oxidative stress and vascular factors. Thrombosis amplifies inflammation, and exaggerated inflammatory processes can trigger thrombosis mainly due to the activation of leukocytes, platelets, and endothelial cells. APE-related endothelium injury is a major trigger for immune system activation. Endothelium is also a key component mediating inflammatory reaction and it is relevant to maintain vascular permeability. Exaggerated right ventricular wall stress and overload, with coexisting systemic hypotension and hypoxemia, result in myocardial injury and necrosis. Hypoxia, tissue factor activation and cytokine storm are engaged in the thrombo-inflammatory processes. Thrombus development is characterized by inflammatory state vascular wall caused mainly by an early extravasation of leukocytes and intense selectins and cytokines production. Nevertheless, immunity of DVT is well described, little is known about potential chemokine and cellular differences between thrombus that develops in the vein and thrombus that detaches and lodges in the pulmonary circulation being a cause of APE. There is a paucity of data considering inflammatory state in the pulmonary artery wall during an acute episode of pulmonary embolism. The main aim of this review is to summarize the knowledge of immunity in acute phase of pulmonary embolism in experimental models.
Topics: Animals; Endothelial Cells; Pulmonary Embolism; Thrombosis; Inflammation; Models, Animal; Hominidae
PubMed: 38299563
DOI: 10.2478/aite-2024-0003 -
Journal of Neuroinflammation Mar 2024The retinal pigment epithelium (RPE) maintains photoreceptor viability and function, completes the visual cycle, and forms the outer blood-retinal barrier (oBRB). Loss...
The retinal pigment epithelium (RPE) maintains photoreceptor viability and function, completes the visual cycle, and forms the outer blood-retinal barrier (oBRB). Loss of RPE function gives rise to several monogenic retinal dystrophies and contributes to age-related macular degeneration. Retinal detachment (RD) causes separation of the neurosensory retina from the underlying RPE, disrupting the functional and metabolic relationships between these layers. Although the retinal response to RD is highly studied, little is known about how the RPE responds to loss of this interaction. RNA sequencing (RNA-Seq) was used to compare normal and detached RPE in the C57BL6/J mouse. The naïve mouse RPE transcriptome was compared to previously published RPE signature gene lists and from the union of these 14 genes (Bmp4, Crim1, Degs1, Gja1, Itgav, Mfap3l, Pdpn, Ptgds, Rbp1, Rnf13, Rpe65, Slc4a2, Sulf1 and Ttr) representing a core signature gene set applicable across rodent and human RPE was derived. Gene ontology enrichment analysis (GOEA) of the mouse RPE transcriptome identified expected RPE features and functions, such as pigmentation, phagocytosis, lysosomal and proteasomal degradation of proteins, and barrier function. Differentially expressed genes (DEG) at 1 and 7 days post retinal detachment (dprd) were defined as mRNA with a significant (p≤0.05) fold change (FC) of 0.67 ≥ FC ≥ 1.5 in detached versus naïve RPE. The RPE transcriptome exhibited dramatic changes at 1 dprd, with 2297 DEG identified. The KEGG pathways and biological process GO groups related to innate immune responses were significantly enriched. Lipocalin 2 (Lcn2) and several chemokines were upregulated, while numerous genes related to RPE functions, such as pigment synthesis, visual cycle, phagocytosis, and tight junctions were downregulated at 1 dprd. The response was largely transient, with only 18 significant DEG identified at 7 dprd, including upregulation of complement gene C4b. Validation studies confirmed RNA-Seq results. Thus, the RPE quickly downregulates cell-specific functions and mounts an innate immune defense response following RD. Our data demonstrate that the RPE contributes to the inflammatory response to RD and may play a role in attraction of immune cells to the subretinal space.
Topics: Mice; Animals; Humans; Retinal Pigment Epithelium; Retinal Detachment; Retina; Macular Degeneration; Phagocytosis; Bone Morphogenetic Protein Receptors
PubMed: 38528525
DOI: 10.1186/s12974-024-03062-2 -
American Journal of Ophthalmology Case... Dec 2023To report a rare case of uveal effusion syndrome following COVID-19 vaccination.
PURPOSE
To report a rare case of uveal effusion syndrome following COVID-19 vaccination.
OBSERVATION
A 71-year-old Asian man presented to his ophthalmologist with blurred vision and noticing distorted lines in his left eye two weeks after the first dose of COVID-19 vaccination. Examination revealed choroidal detachment and he was advised systemic corticosteroids. The symptoms were ignored and the second vaccine dose was taken. After five months, he presented to our clinic with persistent visual complaints. He also had a history of COVID-19 infection three months prior to vaccination. Ocular examination revealed a quiet anterior chamber with annular choroidal detachment consistent with the diagnosis of Type 3 uveal effusion syndrome. B-scan ultrasonography revealed increased choroidal thickness with detachment. Optical coherence tomography showed subretinal fluid with retinal pigment epithelium and choroidal folds. Ultrasound biomicroscopy revealed all around supraciliary effusion in the left eye. The patient was treated with oral prednisolone and mycophenolate mofetil which resulted in complete resolution of uveal effusion and improvement in visual acuity.
CONCLUSIONS AND IMPORTANCE
Uveal effusion syndrome is a rare ocular disease, however it may manifest following COVID-19 vaccination. Our case highlights the importance of a complete ophthalmic examination in patients with ocular symptoms after vaccination.
PubMed: 38161517
DOI: 10.1016/j.ajoc.2023.101884 -
Indian Journal of Ophthalmology Aug 2023
Topics: Humans; Vitreoretinal Surgery; Retinal Diseases; Retinal Detachment; Retinal Artery Occlusion
PubMed: 37530292
DOI: 10.4103/IJO.IJO_231_23 -
Retinal Cases & Brief Reports Nov 2023To describe a case of chronic pediatric retinal detachment with multiple macrocysts, its surgical management, and a review of the literature. (Review)
Review
PURPOSE
To describe a case of chronic pediatric retinal detachment with multiple macrocysts, its surgical management, and a review of the literature.
METHODS
Case report with fundus photography and optical coherence tomography.
RESULTS
We describe a case of an asymptomatic, 11-year-old boy with a chronic rhegmatogenous retinal detachment with multiple peripheral macrocysts. The patient had counting fingers visual acuity on presentation. The detachment was successfully surgically repaired with scleral buckling, subretinal fluid drainage, cryotherapy, and a SF6 tamponade. At the 12-month follow-up, the retina remained attached with improvement of visual acuity to 20/100 with resolution of the cysts. Optical coherence tomography revealed loss of macular ellipsoid zone. Genetic testing revealed a heterozygous dominant COL11A1 mutation.
CONCLUSION
To the authors' knowledge, this is the first reported case of chronic retinal detachment presenting with multiple peripheral macrocysts in a pediatric patient with Stickler syndrome. More research is needed into the cause and significance of retinal macrocysts, particularly in the pediatric population.
Topics: Male; Humans; Child; Retinal Detachment; Scleral Buckling; Retina; Visual Acuity; Cryotherapy; Vitrectomy; Tomography, Optical Coherence
PubMed: 35972836
DOI: 10.1097/ICB.0000000000001288 -
Frontiers in Microbiology 2023Plant breeding is used to develop crops with host resistance to aphids, however, virulent biotypes often develop that overcome host resistance genes. We tested whether...
Plant breeding is used to develop crops with host resistance to aphids, however, virulent biotypes often develop that overcome host resistance genes. We tested whether the symbionts, () and (), affect virulence and fecundity in soybean aphid biotypes Bt1 and Bt3 cultured on whole plants and detached leaves of three resistant, , and and one susceptible, , soybean genotypes. Whole plants and individual aphid experiments of with and without and did not show differences in overall fecundity. Differences were observed in peak fecundity, first day of deposition, and day of maximum nymph deposition of individual aphids on detached leaves. Bt3 had higher fecundity than Bt1 on detached leaves of all plant genotypes regardless of bacterial profile. Symbionts did not affect peak fecundity of Bt1 but increased it in Bt3 (++) and all Bt3 strains began to deposit nymphs earlier than the Bt1 (+-). in Bt1 delayed the first day of nymph deposition in comparison to aposymbiotic Bt1 except when reared on . For the Bt1 and Bt3 strains, symbionts did not result in a significant difference in the day they deposited the maximum number of nymphs nor was there a difference in survival or variability in number of nymphs deposited. Variability of number of aphids deposited was higher in aphids feeding on resistant plant genotypes. The impact of on soybean aphid patterns of fecundity was dependent on the aphid biotype and plant genotype. alone had no detectable impact but may have contributed to the increased fecundity of Bt3 (++). An individual based model, using data from the detached leaves experiment and with intraspecific competition removed, found patterns similar to those observed in the greenhouse and growth chamber experiments including a significant interaction between soybean genotype and aphid strain. Combining individual data with the individual based model of population growth isolated the impact of fecundity and host resistance from intraspecific competition and host health. Changes to patterns of fecundity, influenced by the composition and concentration of symbionts may contribute to competitive interactions among aphid genotypes and influence selection on virulent aphid populations.
PubMed: 37720159
DOI: 10.3389/fmicb.2023.1209595 -
The Journal of Biological Chemistry Dec 2023Lipid rafts are highly ordered membrane domains that are enriched in cholesterol and glycosphingolipids and serve as major platforms for signal transduction. Cell...
Lipid rafts are highly ordered membrane domains that are enriched in cholesterol and glycosphingolipids and serve as major platforms for signal transduction. Cell detachment from the extracellular matrix (ECM) triggers lipid raft disruption and anoikis, which is a barrier for cancer cells to metastasize. Compared to single circulating tumor cells (CTCs), our recent studies have demonstrated that CD44-mediatd cell aggregation enhances the stemness, survival and metastatic ability of aggregated cells. Here, we investigated whether and how lipid rafts are involved in CD44-mediated cell aggregation. We found that cell detachment, which mimics the condition when tumor cells detach from the ECM to metastasize, induced lipid raft disruption in single cells, but lipid raft integrity was maintained in aggregated cells. We further found that lipid raft integrity in aggregated cells was required for Rac1 activation to prevent anoikis. In addition, CD44 and γ-secretase coexisted at lipid rafts in aggregated cells, which promoted CD44 cleavage and generated CD44 intracellular domain (CD44 ICD) to enhance stemness of aggregated cells. Consequently, lipid raft disruption inhibited Rac1 activation, CD44 ICD generation, and metastasis. Our findings reveal two new pathways regulated by CD44-mediated cell aggregation via maintaining lipid raft integrity. These findings also suggest that targeting cell aggregation-mediated pathways could be a novel therapeutic strategy to prevent CTC cluster-initiated metastasis.
Topics: Cell Aggregation; Extracellular Matrix; Membrane Microdomains; Monomeric GTP-Binding Proteins; Signal Transduction; MDA-MB-231 Cells; Humans; Animals; Mice; Cell Line, Tumor; Mice, Inbred BALB C; Hyaluronan Receptors; rac1 GTP-Binding Protein; Anoikis; Enzyme Activation; Neoplasm Metastasis
PubMed: 37866630
DOI: 10.1016/j.jbc.2023.105377 -
PLoS Computational Biology Jul 2023Muscle myosin is a non-processive molecular motor that generates mechanical work when cooperating in large ensembles. During its cyle, each individual motor keeps...
Muscle myosin is a non-processive molecular motor that generates mechanical work when cooperating in large ensembles. During its cyle, each individual motor keeps attaching and detaching from the actin filament. The random nature of attachment and detachment inevitably leads to losses and imposes theoretical limits on the energetic efficiency. Here, we numerically determine the theoretical efficiency limit of a classical myosin model with a given number of mechano-chemical states. All parameters that are not bounded by physical limits (like rate limiting steps) are determined by numerical efficiency optimization. We show that the efficiency is limited by the number of states, the stiffness and the rate-limiting kinetic steps. There is a trade-off between speed and efficiency. Slow motors are optimal when most of the available free energy is allocated to the working stroke and the stiffness of their elastic element is high. Fast motors, on the other hand, work better with a lower and asymmetric stiffness and allocate a larger fraction of free energy to the release of ADP. Overall, many features found in myosins coincide with the findings from the model optimization: there are at least 3 bound states, the largest part of the working stroke takes place during the first transition, the ADP affinity is adapted differently in slow and fast myosins and there is an asymmetry in elastic elements.
Topics: Myosins; Actin Cytoskeleton; Muscles; Kinetics; Actins
PubMed: 37478158
DOI: 10.1371/journal.pcbi.1011310 -
Molecular and Clinical Oncology Sep 2023Breast cancer stands as the most prevalent form of cancer affecting women, with metastasis serving as a leading cause of mortality among patients with breast cancer.... (Review)
Review
Breast cancer stands as the most prevalent form of cancer affecting women, with metastasis serving as a leading cause of mortality among patients with breast cancer. Gaining a comprehensive understanding of the metastatic mechanism in breast cancer is essential for early detection and precision treatment of the disease. Circulating tumor cells (CTCs) play a vital role in this context, representing cancer cells that detach from tumor tissues and enter the bloodstream of cancer patients. These cells travel in the blood circulation as single cells or clusters. Recent research has shed light on the enhanced metastatic potential of CTC clusters compared to single CTCs, despite their limited occurrence. The aim of the present review was to explore recent findings on CTCs with a particular focus on the clustering phenomenon of CTCs observed in breast cancer. Additionally, the present review delved into the comparison between single CTCs and CTC clusters regarding their implications for the treatment and prognosis of patients diagnosed with metastatic breast cancer. By examining the role and mechanisms of CTCs in breast cancer metastasis, the present review provided an improved understanding of CTCs and their significance in early detection of breast cancer metastasis through peripheral blood analysis. Moreover, it contributed to the comprehension of cancer prognosis and prediction by highlighting the implications of CTCs in these aspects. Ultimately, the present study seeks to advance knowledge in the field and pave the way for improved approaches to breast cancer management.
PubMed: 37614367
DOI: 10.3892/mco.2023.2667 -
Polymers Oct 2023Supramolecular responsive microcarriers based on chitosan microspheres were prepared and applied for nonenzymatic cell detachment. Briefly, chitosan microspheres (CSMs)...
Supramolecular responsive microcarriers based on chitosan microspheres were prepared and applied for nonenzymatic cell detachment. Briefly, chitosan microspheres (CSMs) were first prepared by an emulsion crosslinking approach, the surface of which was then modified with β-cyclodextrin (β-CD) by chemical grafting. Subsequently, gelatin was attached onto the surface of the CSMs via the host-guest interaction between β-CD groups and aromatic residues in gelatin. The resultant microspheres were denoted CSM-g-CD-Gel. Due to their superior biocompatibility and gelatin niches, CSM-g-CD-Gel microspheres can be used as effective microcarriers for cell attachment and expansion. L-02, a human fetal hepatocyte line, was used to evaluate cell attachment and expansion with these microcarriers. After incubation for 48 h, the cells attached and expanded to cover the entire surface of microcarriers. Moreover, with the addition of adamantane (AD), cells can be detached from the microcarriers together with gelatin because of the competitive binding between β-CD and AD. Overall, these supramolecular responsive microcarriers could effectively support cell expansion and achieve nonenzymatic cell detachment and may be potentially reusable with a new cycle of gelatin attachment and detachment.
PubMed: 37836073
DOI: 10.3390/polym15194024