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Cancer Science Jun 2022Cells detached from the extracellular matrix (ECM) can trigger different modes of cell death, and the survival of ECM-detached cells is one of the prerequisites for the...
Cells detached from the extracellular matrix (ECM) can trigger different modes of cell death, and the survival of ECM-detached cells is one of the prerequisites for the metastatic cascade. Ferroptosis, a form of iron-dependent programmed cell death, has recently been found to be involved in matrix-detached cancer cells. However, the molecular mechanisms by which ECM-detached cells escape ferroptosis are not fully understood. Here, we observed that cell migration-inducing protein (CEMIP) upregulation facilitates ferroptosis resistance during ECM detachment by promoting cystine uptake in prostate cancer (PCa) cells. Meanwhile, silencing CEMIP causes it to lose its ability to promote cystine uptake and inhibit ferroptosis. Mechanistically, the interaction of CEMIP with inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) modulates calcium ion (Ca ) leakage from the endoplasmic reticulum, activating calcium/calmodulin-dependent protein kinase II (CaMKII), which further facilitates nuclear factor erythroid 2-related factor 2 (NRF2) phosphorylation and nuclear localization, leading to elevated transcription of solute carrier family 7 member 11 (SLC7A11), a glutamate/cystine antiporter, in PCa cells. Our findings delineate a novel role of CEMIP in ferroptosis resistance during ECM detachment and provide new insights into therapeutic strategies for metastatic PCa.
Topics: Calcium; Cell Movement; Cell Survival; Cystine; Extracellular Matrix; Ferroptosis; Humans; Male; Prostatic Neoplasms
PubMed: 35363929
DOI: 10.1111/cas.15356 -
Microbiology Spectrum Feb 2022Patients with chronic respiratory diseases use home nebulizers that are often contaminated with pathogenic microbes to deliver aerosolized medications. The conditions...
Patients with chronic respiratory diseases use home nebulizers that are often contaminated with pathogenic microbes to deliver aerosolized medications. The conditions under which these microbes leave the surface as bioaerosols during nebulization are not well characterized. The objectives of this study were to (i) determine whether different pathogens detach and disperse from the nebulizer surface during aerosolization and (ii) measure the effects of relative humidity and drying times on bacterial surface detachment and aerosolization. Bacteria were cultured from bioaerosols after Pari LC Plus albuterol nebulization using two different sources, as follows: (i) previously used nebulizers donated by anonymous patients with cystic fibrosis (CF) and (ii) nebulizers inoculated with bacteria isolated from the lungs of CF patients. Fractionated bioaerosols were collected with a Next-Generation Impactor. For a subset of bacteria, surface adherence during rewetting was measured with fluorescence microscopy. Bacteria dispersed from the surface of used CF patient nebulizers during albuterol nebulization. Eighty percent (16/20) of clinical isolates inoculated on the nebulizer in the laboratory formed bioaerosols. Detachment from the plastic surface into the chamber solution predicted bioaerosol production. Increased relative humidity and decreased drying times after inoculation favored bacterial dispersion on aerosols during nebulized therapy. Pathogenic bacteria contaminating nebulizer surfaces detached from the surface as bioaerosols during nebulized therapies, especially under environmental conditions when contaminated nebulizers were dried or stored at high relative humidity. This finding emphasizes the need for appropriate nebulizer cleaning, disinfection, and complete drying during storage and informs environmental conditions that favor bacterial surface detachment during nebulization. Studies from around the world have demonstrated that many patients use contaminated nebulizers to deliver medication into their lungs. While it is known that using contaminated medications in a nebulizer can lead to a lung infection, whether bacteria on the surface of a contaminated nebulizer detach as bioaerosols capable of reaching the lung has not been studied. This work demonstrates that a subset of clinical bacteria enter solution from the surface during nebulization and are aerosolized. Environmental conditions of high relative humidity during storage favor dispersion from the surface. We also provide results of an assay conducted to monitor bacterial surface detachment during multiple cycles of rewetting that correlate with the results of nebulizer/bacterial surface interactions. These studies demonstrate for the first time that pathogenic bacteria on the nebulizer surface pose a risk of bacterial inhalation to patients who use contaminated nebulizers.
Topics: Aerosols; Bacteria; Bacterial Adhesion; Cystic Fibrosis; Equipment Contamination; Humans; Nebulizers and Vaporizers
PubMed: 35107362
DOI: 10.1128/spectrum.02535-21 -
NeuroImage Aug 2020In neuroscience, empathy is often conceived as relatively automatic. The voluntary control that people can exert on brain mechanisms that map the emotions of others onto...
In neuroscience, empathy is often conceived as relatively automatic. The voluntary control that people can exert on brain mechanisms that map the emotions of others onto our own emotions has received comparatively less attention. Here, we therefore measured brain activity while participants watched emotional Hollywood movies under two different instructions: to rate the main characters' emotions by empathizing with them, or to do so while keeping a detached perspective. We found that participants yielded highly consistent and similar ratings of emotions under both conditions. Using intersubject correlation-based analyses we found that, when encouraged to empathize, participants' brain activity in limbic (including cingulate and putamen) and somatomotor regions (including premotor, SI and SII) synchronized more during the movie than when encouraged to detach. Using intersubject functional connectivity we found that comparing the empathic and detached perspectives revealed widespread increases in functional connectivity between large scale networks. Our findings contribute to the increasing awareness that we have voluntary control over the neural mechanisms through which we process the emotions of others.
Topics: Adult; Brain; Empathy; Humans; Magnetic Resonance Imaging; Male; Motion Pictures; Photic Stimulation; Young Adult
PubMed: 31931155
DOI: 10.1016/j.neuroimage.2020.116529 -
BMJ Case Reports Feb 2022Here is presented a unique case of bilateral serous macular detachments as a side effect of topical travoprost (0.004%) therapy. Only three other cases in the literature...
Here is presented a unique case of bilateral serous macular detachments as a side effect of topical travoprost (0.004%) therapy. Only three other cases in the literature have definitively associated this side effect with other topical prostaglandins. The aetiological and pathophysiological pathways remain to be clearly elucidated but are potentially related to increased choroidal vascular permeability. In this case, the subretinal fluid resolved rapidly and completely after cessation of travoprost drops, showing it to be a reversible pathology similar to prostaglandin-associated cystoid macular oedema. This uncommon association is therefore important to consider in the differential diagnosis of serous macular detachment. Increasing ophthalmic awareness could help to prevent unnecessary investigations in undifferentiated patients without other guiding historical or examination features. This may save time and expense for the patient and health systems.
Topics: Fluorescein Angiography; Humans; Retinal Detachment; Subretinal Fluid; Tomography, Optical Coherence; Travoprost
PubMed: 35110285
DOI: 10.1136/bcr-2021-246712 -
American Journal of Clinical and... 2021A major metastasis suppressing mechanism is the rapid apoptotic death of cancer cells upon detachment from extracellular matrix, a process called anoikis. Focal adhesion...
A major metastasis suppressing mechanism is the rapid apoptotic death of cancer cells upon detachment from extracellular matrix, a process called anoikis. Focal adhesion kinase (PTK2/FAK) is a key enzyme involved in evasion of anoikis. We show that loss of the Cub-domain containing protein-1 (CDCP1), paradoxically stimulates FAK activation in the detached state of prostate cancer cells. In CDCP1 DU145 and PC3 prostate cancer cells, detachment-activation of FAK occurs through local production of PI(4,5)P. PI(4,5)P is generated by the PIP5K1c-201 splicing isoform of PIP5K1c, which contains a unique SRC phosphorylation site. In the detached state, reduced expression of CDCP1 and an alternative CDCP1-independent SRC activation mechanism triggers PIP5K1c-pY644 phosphorylation by SRC. This causes a switch of Talin binding from β1-integrin to PIP5K1c-pY644 and leads to activation of PIP5K1c-FAK. Reduced CDCP1 expression also inactivates CDK5, a negative regulator of PIP5K1c. Furthermore, immersion of prostate cancer cells in 10% human plasma or fetal bovine serum is required for activation of PIP5K1c-FAK. The PIP5K1c induced detachment-activation of FAK in preclinical models sensitizes CDCP1 prostate cancer cells to FAK inhibitors. In patients, CDCP1 versus CDCP1 circulating tumor cells differ in expression of and oncogenes and TMPRSS2 and display intra-patient heterogeneity of FAK-pY397 expression. Taken together, CDCP1 and CDCP1 detached prostate cancer cells activate distinct cytoplasmic kinase complexes and targetable transcription factors, which has important therapeutic implications.
PubMed: 34541033
DOI: No ID Found -
Acta Ophthalmologica Nov 2014To investigate pathomechanisms involved in graft detachment after Descemet's membrane endothelial keratoplasty (DMEK) and its clinical implications.
PURPOSE
To investigate pathomechanisms involved in graft detachment after Descemet's membrane endothelial keratoplasty (DMEK) and its clinical implications.
METHODS
In a prospective case series, 30 eyes with Fuchs' endothelial dystrophy underwent DMEK. Intraoperatively obtained recipients' endothelium-Descemet's membranes (EDMs) were investigated histologically and immunohistochemically. The postoperative donor graft status was categorized as attached or detached. Clinical and morphological parameters were analysed between the study groups.
RESULTS
The detachment rate was 40% (12/30). There was no significant difference in postoperative visual acuity between the groups, but visual recovery was delayed in eyes with initially detached grafts. Gender, age, preoperative central corneal thickness or best corrected visual acuity did not influence the detachment rate. However, separation and disruption of the anterior banded layer (ABL) were frequently observed in patients with graft detachment, and ABL thickness was identified as a significant predictor for graft detachment. The ABL thickness was 2.5 ± 0.9 μm and 3.5 ± 1.6 μm in patients with attached and detached grafts, respectively. Immunohistologically, a deficiency of fibronectin and cytokeratin was observed within the ABL of patients with detached grafts. In contrast, a complete removal of the EDM with residual stromal collagen fragments was observed in patients with adherent grafts.
CONCLUSIONS
Incomplete removal of the EDM, with residual ABL fragments on the recipients' corneal stroma, may be a risk factor for graft detachment after DMEK. The separation and disruption of the ABL might be promoted by a deficiency of matrix proteins, stronger biomechanical properties and a firm adherence to the posterior corneal stroma.
Topics: Aged; Aged, 80 and over; Biomarkers; Corneal Endothelial Cell Loss; Descemet Membrane; Descemet Stripping Endothelial Keratoplasty; Endothelium, Corneal; Female; Fluorescent Antibody Technique, Indirect; Fuchs' Endothelial Dystrophy; Graft Rejection; Humans; Male; Middle Aged; Postoperative Complications; Prospective Studies; Risk Factors; Visual Acuity
PubMed: 24725459
DOI: 10.1111/aos.12419 -
Biomimetics (Basel, Switzerland) Jan 2023Easy detachment is as important as reliable an attachment to climbing robots in achieving stable climbing on vertical surfaces. To deal with the difficulty of detachment...
Easy detachment is as important as reliable an attachment to climbing robots in achieving stable climbing on vertical surfaces. To deal with the difficulty of detachment occurring in wheeled and track-type climbing robots using bio-inspired spines, a novel climbing robot utilizing spiny track and dual-rail mechanism is proposed in this paper. The spiny track consists of dozens of spiny feet, and the movement of each spiny foot is guided by the specially designed dual-rail mechanism to achieve reliable attachment and easy detachment. First, the design of the climbing robot and the dual-rail mechanism are presented. Then, the dual-rail model is constructed to analyze the attaching and detaching movements of the spiny feet, and a mechanical model is established to analyze the force distribution on the spiny track. Finally, a robot prototype is developed, and the analysis results are verified by the experiment results. Experiments on the prototype demonstrated that it could climb on various rough vertical surfaces at a speed of 36 mm/s, including sandpaper, brick surfaces, concrete walls with pebbles, and coarse stucco walls.
PubMed: 36648800
DOI: 10.3390/biomimetics8010014 -
Frontiers in Neuroscience 2020One may notice a relatively wide range of tactile sensations even when touching the same hard, flat surface in similar ways. Little is known about the reasons for this...
One may notice a relatively wide range of tactile sensations even when touching the same hard, flat surface in similar ways. Little is known about the reasons for this variability, so we decided to investigate how the perceptual intensity of light stickiness relates to the physical interaction between the skin and the surface. We conducted a psychophysical experiment in which nine participants actively pressed their finger on a flat glass plate with a normal force close to 1.5 N and detached it after a few seconds. A custom-designed apparatus recorded the contact force vector and the finger contact area during each interaction as well as pre- and post-trial finger moisture. After detaching their finger, participants judged the stickiness of the glass using a nine-point scale. We explored how sixteen physical variables derived from the recorded data correlate with each other and with the stickiness judgments of each participant. These analyses indicate that stickiness perception mainly depends on the pre-detachment pressing duration, the time taken for the finger to detach, and the impulse in the normal direction after the normal force changes sign; finger-surface adhesion seems to build with pressing time, causing a larger normal impulse during detachment and thus a more intense stickiness sensation. We additionally found a strong between-subjects correlation between maximum real contact area and peak pull-off force, as well as between finger moisture and impulse.
PubMed: 32372893
DOI: 10.3389/fnins.2020.00235 -
La Tunisie Medicale Feb 2023To estimate metamorphopsia prevalence, predictors and etiologies in patients operated for rhegmatogenous retinal detachment (RRD) with detached macula with successful...
AIM
To estimate metamorphopsia prevalence, predictors and etiologies in patients operated for rhegmatogenous retinal detachment (RRD) with detached macula with successful results.
METHODS
Retrospective study including 50 eyes of 50 patients who underwent pars plana vitrectomy for RRD with detached macula with standard silicone oil (SO) tamponade. Patients who had successful surgery with durable anatomic reapplication of the retina after SO removal were included. Patients were examined on day 1, day 7,1 month, and 3 months after surgery. Best corrected visual acuity, Amsler grid, fundus biomicroscopy, Spectral Domain Optical Coherence Tomography (SD-OCT) and fundus auto-fluorescence (FAF) were performed in all patients after surgery. Structural abnormalities such as macular folds, macular epiretinal membrane, cystoid macular edema, and foveal disruption of the ellipsoid layer were observed on SD-OCT. Macular displacement was identified on FAF.
RESULTS
We identified metamorphopsia as post-operative visual impairment in 27 patients among 50 (54%). Clinical assessment found that a delay > 7 days between symptoms and surgery (p < 0.001), more than 2 detached quadrants (p=0.012), and stage C of proliferative vitreoretinopathy (p=0.035) were associated to metamorphopsia. Regarding multimodal imaging findings, only macular folds and macular displacement were significantly correlated with the occurrence of postoperative metamorphopsia (p <0.001).
CONCLUSION
Metamorphopsia is a common complaint after vitrectomy for RRD. Macular rotation and folds would be the main causes after complete and durable reapplication of the retina.
Topics: Humans; Retinal Detachment; Vitrectomy; Prevalence; Retrospective Studies; Vision, Low
PubMed: 37682273
DOI: No ID Found -
Retina (Philadelphia, Pa.) Nov 2018This review aimed to determine the optimal management of retinal pigment epithelial detachments (PEDs) in neovascular age-related macular degeneration (nAMD) based on... (Review)
Review
PURPOSE
This review aimed to determine the optimal management of retinal pigment epithelial detachments (PEDs) in neovascular age-related macular degeneration (nAMD) based on review of available evidence in the literature.
METHODS
A comprehensive literature review evaluates previous retrospective and prospective studies that assessed the treatment of PEDs in nAMD.
RESULTS
Studies illustrated that anti-vascular endothelial growth factor (VEGF) therapy can be effective in eyes with PED secondary to nAMD. Similar visual outcomes are associated with different anti-VEGF treatments. Higher anti-VEGF doses may improve anatomical response, without correlation with vision improvement. Fibrovascular PEDs may be difficult to treat, but even these eyes can gain vision with anti-VEGF therapy. A retinal pigment epithelial tear may develop in 15% to 20% of eyes with PEDs after anti-VEGF therapy, especially in PEDs greater than 500 µm to 600 µm in height; however, vision may stabilize with continued therapy. Atrophy may complicate eyes with PED and nAMD after anti-VEGF therapy, especially in association with complete PED resolution.
CONCLUSION
Available literature suggests that anti-VEGF therapy is safe and efficacious for PED and nAMD. Treatment should focus on vision gains rather than PED resolution because there is no apparent correlation between anatomical and functional improvement in most eyes with PED and nAMD.
Topics: Angiogenesis Inhibitors; Bevacizumab; Fluorescein Angiography; Humans; Intravitreal Injections; Ranibizumab; Retinal Detachment; Retinal Pigment Epithelium; Tomography, Optical Coherence; Vascular Endothelial Growth Factor A; Visual Acuity; Wet Macular Degeneration
PubMed: 29697591
DOI: 10.1097/IAE.0000000000002195