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Advanced Science (Weinheim,... Sep 2023When circulating tumor cells (CTCs) travel in circulation, they can be killed by detachment-induced anoikis and fluidic shear stress (SS)-mediated apoptosis. Circulatory...
When circulating tumor cells (CTCs) travel in circulation, they can be killed by detachment-induced anoikis and fluidic shear stress (SS)-mediated apoptosis. Circulatory treatment, which can make CTCs detached but also generate SS, can increase metastasis of cancer cells. To identify SS-specific mechanosensors without detachment impacts, a microfluidic circulatory system is used to generate arteriosus SS and compare transcriptome profiles of circulating lung cancer cells with suspended cells. Half of the cancer cells can survive SS damage and show higher invasion ability. Mesotrypsin (PRSS3), protease-activated receptor 2 (PAR2), and the subunit of activating protein 1, Fos-related antigen 1 (FOSL1), are upregulated by SS, and their high expression is responsible for promoting invasion and metastasis. SS triggers PRSS3 to cleave the N-terminal inhibitory domain of PAR2 within 2 h. As a G protein-coupled receptor, PAR2 further activates the Gα protein to turn on the Src-ERK/p38/JNK-FRA1/cJUN axis to promote the expression of epithelial-mesenchymal transition markers, and also PRSS3, which facilitates metastasis. Enriched PRSS3, PAR2, and FOSL1 in human tumor samples and their correlations with worse outcomes reveal their clinical significance. PAR2 may serve as an SS-specific mechanosensor cleavable by PRSS3 in circulation, which provides new insights for targeting metastasis-initiating CTCs.
Topics: Humans; Cell Line, Tumor; Lung Neoplasms; Neoplastic Cells, Circulating; Receptor, PAR-2; Receptors, G-Protein-Coupled; Trypsin
PubMed: 37395651
DOI: 10.1002/advs.202301059 -
Nature Communications Oct 2023Crystal dissolution, which is a fundamental process in both natural and technological settings, has been predominately viewed as a process of ion-by-ion detachment into...
Crystal dissolution, which is a fundamental process in both natural and technological settings, has been predominately viewed as a process of ion-by-ion detachment into a surrounding solvent. Here we report a mechanism of dissolution by particle detachment (DPD) that dominates in mesocrystals formed via crystallization by particle attachment (CPA). Using liquid phase electron microscopy to directly observe dissolution of hematite crystals - both compact rhombohedra and mesocrystals of coaligned nanoparticles - we find that the mesocrystals evolve into branched structures, which disintegrate as individual sub-particles detach. The resulting dissolution rates far exceed those for equivalent masses of compact single crystals. Applying a numerical generalization of the Gibbs-Thomson effect, we show that the physical drivers of DPD are curvature and strain inherently tied to the original CPA process. Based on the generality of the model, we anticipate that DPD is widespread for both natural minerals and synthetic crystals formed via CPA.
PubMed: 37813861
DOI: 10.1038/s41467-023-41443-y -
Irish Journal of Medical Science Feb 2024Acute retinal necrosis (ARN) is a progressive necrotizing retinitis caused by viral infection. Optimal management strategies have not been established for this... (Review)
Review
BACKGROUND
Acute retinal necrosis (ARN) is a progressive necrotizing retinitis caused by viral infection. Optimal management strategies have not been established for this detrimental disease. Previous literature published suggests that Varicella-zoster virus (VZV) and Herpes simplex virus-1 (HSV1) are the most common promoters of acute retinal necrosis (ARN).
AIMS
The purpose of our study was to investigate the viral distribution, demographic, and treatment outcomes of ARN.
METHODS
A retrospective chart review evaluated data from PCR-positive ARN patients diagnosed between 2009 and 2018.
RESULTS
Analysis of fourteen eyes from 12 patients found CMV and VZV as the commonest causes of ARN. Patients on 1 g of valacyclovir three times a day (V1T) had worse vision between first and final visits (mean difference of 1.25 ± 0.65, n = 2) compared with patients treated with 2 g of valacyclovir three times a day (V2T), or 900 mg twice a day of valganciclovir (V9B) (mean difference of - 0.067 ± 0.13, n = 6, and 0.067 ± 0.067, n = 6, respectively). Both V1T patients developed retinal detachments (RD). Both CMV patients treated with intravitreal triamcinolone developed ARN, elevated IOP, and one developed multiple RD.
CONCLUSIONS
Our review found increased incidence of CMV-positive ARN. Patients with zone 1 disease had worse initial visual acuity. Moreover, patients had more favorable outcomes with V2T and V9B compared to V1T. CMV-positive patients clinically worsened after intravitreal steroid injections, further underscoring the value of a PCR diagnosis to tailor the patients' treatment plan accordingly.
Topics: Humans; Retinal Necrosis Syndrome, Acute; Valacyclovir; Retrospective Studies; Herpesvirus 3, Human; Retinal Detachment; Treatment Outcome; Polymerase Chain Reaction; Cytomegalovirus Infections
PubMed: 37365446
DOI: 10.1007/s11845-023-03426-2 -
Survey of Ophthalmology 2024Proliferative vitreoretinopathy (PVR) is an abnormal and prolonged healing response to retinal injury (retinal detachment, post retinal detachment surgery)... (Review)
Review
Proliferative vitreoretinopathy (PVR) is an abnormal and prolonged healing response to retinal injury (retinal detachment, post retinal detachment surgery) characterised by: pre/subretinal membrane formation; retinal gliosis and retinal shortening, retinal pigment epithelium cell proliferation; and increased glial (mainly Mu¨ller cells), fibroblast and inflammatory cell (macrophage, lymphocyte) activity, leading to tractional retinal holes/breaks and multiple costly eye operations suffered by patients. PVR can cause retinal re-detachment following primary surgical intervention for rhegmatogenous retinal detachment. Vitrectomy and scleral buckling surgery are the main approaches for treating PVR complications of retinal detachment. Patients require many operations to remove the scar tissue but vision results are suboptimal, and do not meet patient expectations. Over the past 40 years, this has been one of the greatest challenges for vitreoretinal surgeons and patients. Despite previous large clinical trials of multiple candidate drug therapeutics, no proven adjunctive treatment currently exists to either prevent, reduce, or treat PVR formation in retinal detachment. Both cellular proliferation and the intraocular inflammatory response are realistic targets for adjunctive treatments in PVR. The cellular components of PVR periretinal membranes (retinal pigment epithelial, glial, inflammatory and fibroblastic cells) proliferate and are thus targets for antiproliferative agents. In recent years, several new therapeutics have been tested, and we present an updated review of the clinical therapeutics for PVR in retinal detachment.
Topics: Humans; Vitreoretinopathy, Proliferative; Retinal Detachment; Vitrectomy; Angiogenesis Inhibitors
PubMed: 38492583
DOI: 10.1016/j.survophthal.2024.03.007 -
MethodsX Dec 2023Collagen remodelling is a vital process for embryonic development and homoeostatic maintenance of the adult body. Collagen remodelling is a complex process in...
Collagen remodelling is a vital process for embryonic development and homoeostatic maintenance of the adult body. Collagen remodelling is a complex process in fibroblasts, macrophages and other cells, whereby new collagen is secreted and polymerized into fibrils and old collagen is removed by proteolysis and endocytosis. Whereas the production of collagen is well-studied, the removal of collagen is less understood. In this protocol, we describe a method for the quantification of collagen uptake by cells. This protocol is based on the polymerisation of collagen type I-FITC conjugate in cell culture plate wells. Next, unpolymerized collagen is washed away and the cells are added in cell culture media. At this stage, they can be treated with inhibitors and/or stimulants if required. Afterwards, the cells are detached from the collagen using the protease accutase and the FITC signal is quantified using microscopy and/or flow cytometry.•Easy-to-use protocol for the quantitative measurement of collagen uptake in cells.•Cell detachment from collagen is quick and easy with accutase, even with strong adhering cells like macrophages.•Downstream applications can be a wide selection of analysis techniques like microscopy, RNA- and protein isolation, and flow cytometry.
PubMed: 37533791
DOI: 10.1016/j.mex.2023.102288 -
Japanese Journal of Ophthalmology Jan 2024Vitreomacular traction (VMT) has unique presentations in eyes with diabetic retinopathy (DR). This study aimed to investigate the characteristics and clinical course of...
PURPOSE
Vitreomacular traction (VMT) has unique presentations in eyes with diabetic retinopathy (DR). This study aimed to investigate the characteristics and clinical course of VMT in DR.
STUDY DESIGN
A retrospective case series.
METHODS
Thirty eyes from 30 patients with DR and concurrent VMT were retrospectively enrolled. Baseline and final best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) characteristics were reported. Linear regression models were used to analyze the correlating factors for visual outcome.
RESULTS
Of the 30 eyes, a thickened posterior hyaloid membrane was noted in all cases and multi-layered traction from different directions in 14 eyes (46.7%). Twenty-one eyes (70%) had tractional macular retinoschisis, seven (23.3%) had foveal detachment, five (16.7%) had a lamellar macular hole, and three (10%) had a full-thickness macular hole, including two with macular hole retinal detachment. Three eyes had spontaneous release of the VMT within 3 months of observation. For the remaining 27 eyes receiving operations, the VMT, full-thickness macular hole, and serous foveal detachment all resolved postoperatively with residual macular schisis in 6 eyes (22.2%) only. None of the baseline OCT characteristics were associated with postoperative BCVA (P > .05).
CONCLUSIONS
VMT in DR had a thickened posterior hyaloid, and many of them had multi-layered traction and/or concurrent macular retinoschisis. Lamellar macular hole, full-thickness macular hole, or concurrent retinal detachment may also occur. Spontaneous resolution of VMT rarely occurred, and those who underwent operation for VMT had improved vision and macular structures with resolution of the macular hole and retinal detachment.
Topics: Humans; Diabetic Retinopathy; Retinal Perforations; Retrospective Studies; Vitreous Detachment; Retinal Detachment; Retinoschisis; Traction; Vision Disorders; Tomography, Optical Coherence; Diabetes Mellitus
PubMed: 38001367
DOI: 10.1007/s10384-023-01034-2 -
Science (New York, N.Y.) Apr 2024The retractile type IV pilus (T4P) is important for virulence of the opportunistic human pathogen . The single-stranded RNA (ssRNA) phage PP7 binds to T4P and is brought...
The retractile type IV pilus (T4P) is important for virulence of the opportunistic human pathogen . The single-stranded RNA (ssRNA) phage PP7 binds to T4P and is brought to the cell surface through pilus retraction. Using fluorescence microscopy, we discovered that PP7 detaches T4P, which impairs cell motility and restricts the pathogen's virulence. Using cryo-electron microscopy, mutagenesis, optical trapping, and Langevin dynamics simulation, we resolved the structure of PP7, T4P, and the PP7/T4P complex and showed that T4P detachment is driven by the affinity between the phage maturation protein and its bound pilin, plus the pilus retraction force and speed, and pilus bending. Pilus detachment may be widespread among other ssRNA phages and their retractile pilus systems and offers new prospects for antibacterial prophylaxis and therapeutics.
Topics: Humans; Cryoelectron Microscopy; Fimbriae Proteins; Fimbriae, Bacterial; Pseudomonas aeruginosa; RNA Viruses; Pseudomonas Phages; Virus Internalization; Viral Proteins
PubMed: 38574145
DOI: 10.1126/science.adl0635 -
Ophthalmology. Retina Jan 2024Scleral buckling has been a reliable treatment option in the repair of primary rhegmatogenous retinal detachments. Occasionally, patients require scleral buckles (SBs)... (Observational Study)
Observational Study
PURPOSE
Scleral buckling has been a reliable treatment option in the repair of primary rhegmatogenous retinal detachments. Occasionally, patients require scleral buckles (SBs) to be removed for various reasons. While outcomes of SB removal have been investigated in this subset of patients, there has not been any large patient series to reach any conclusions. Long-term sequelae of SB removal are debated in the literature, specifically around the risk of redetachment.
DESIGN
We performed a retrospective, observational study to evaluate the clinical indications for, and outcomes of, SB removal.
PARTICIPANTS
No control patients in this retrospective, observational study.
METHODS
Eighty-six individuals with a history of SB removal from June 1, 2000, to January 1, 2021, were followed from a large academic center and a private, retina-only practice in Chicago. Exclusion criteria were age of < 18 years and unplanned or self-explanted SB removal.
MAIN OUTCOME MEASURES
Data extracted included patient symptoms before SB removal, indications for removal, resolution of symptoms following removal, rate of redetachment, and rate of additional ocular surgery. Secondary outcomes included identifying factors associated with poorer outcomes.
RESULTS
Eighty-six eyes with history of SB removal were included with an average follow-up of 4 years. Approximately 60% were males and the mean age at the time of SB removal was 59 years. Leading indications for removal were exposure (61.63%), infection (20.93%), and diplopia/strabismus (19.77%). The average time from SB placement to removal was 12.28 ± 11.16 years. Most patients requiring SB removal presented with symptoms, specifically of pain and discomfort (65.12%), diplopia (22.09%), and drainage/discharge (18.60%). Of these patients, 86.59% experienced symptom resolution following SB removal. Notably, 6.56% (4 eyes) of all eyes with at least 1 year of follow-up experienced a redetachment requiring surgery. Within this subset, the average time from SB placement to removal was 2.05 ± 2.01 years and time to redetachment following removal was 15.95 ± 25.71 months. Nine percent of all eyes required additional strabismus or oculoplastic surgery.
CONCLUSIONS
Scleral buckle removal provides a high rate of symptomatic relief and low risk of subsequent detachment. Nevertheless, close monitoring is warranted to monitor for recurrent retinal detachments.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Male; Humans; Middle Aged; Adolescent; Female; Scleral Buckling; Retinal Detachment; Diplopia; Retrospective Studies; Treatment Outcome; Visual Acuity; Strabismus
PubMed: 37531997
DOI: 10.1016/j.oret.2023.07.029 -
Journal of Insect Physiology Sep 2023Mosquito larvae display a stereotyped escape response when they rest attached to the water surface. It consists in detaching from the surface and diving, to return to...
Mosquito larvae display a stereotyped escape response when they rest attached to the water surface. It consists in detaching from the surface and diving, to return to the surface after a brief time. It has been shown that this response can be evoked several times, by repeatedly presenting a moving shadow. Diving triggered by a potential danger revealed as a simple bioassay for investigating behavioural responses in mosquito larvae, in particular their ability to learn. In the present work, we describe an automated system, based on video-tracking individuals, and extracting quantitative data of their movements. We validated our system, by reinvestigating the habituation response of larvae of Aedes aegypti reared in the laboratory, and providing original data on field-collected larvae of genera Culex and Anopheles. Habituation could be demonstrated to occur in all the species, even though it was not possible to induce dishabituation in Culex and Anopheles mosquitoes. In addition to non-associative learning, we characterised motor activity in the studied species, thanks to the possibility offered by the tracking system to extract multiple variables. The here-described system and algorithms can be easily adapted to multiple experimental situations and variables of interest.
Topics: Animals; Larva; Aedes; Learning; Anopheles; Culex
PubMed: 37419177
DOI: 10.1016/j.jinsphys.2023.104535 -
Hypertension Research : Official... Dec 2023Congestive heart failure produces fluid volume overload, central and renal venous pressure elevation, and consequently renal congestion, which results in worsening renal...
Congestive heart failure produces fluid volume overload, central and renal venous pressure elevation, and consequently renal congestion, which results in worsening renal function. Pericyte detachment and pericyte-myofibroblast transition (PMT) were linked to renal interstitial fibrosis. Dahl salt-sensitive hypertensive (DahlS) rats are a non-surgical renal congestion model. The relation, however, between renal interstitial damage, pericyte morphology, and PMT in the renal congestion of DahlS rats has not been reported. DahlS rats (8-week-old) were fed normal salt (NS, 0.4% NaCl) or high salt (HS, 4% NaCl), and the left kidney was decapsulated to reduce renal interstitial hydrostatic pressure (RIHP) at 9 weeks old. One week after capsulotomy, both kidneys were analyzed by molecular and histological techniques. Renal pericyte structure was assessed in the body donors with/without venous stasis. Markers of tubulointerstitial damage, interstitial fibrosis, and PMT were upregulated in the right non-decapsulated kidney of DahlS rats fed HS. Renal tubular injury and fibrosis were detected in the HS diet groups in histological analysis. Pericyte detachment was observed in the right non-decapsulated kidney of DahlS rats fed HS by low vacuum-scanning electron microscopy. Decapsulation in DahlS rats fed HS attenuated these findings. Also, renal pericytes detached from the vascular wall in patients with heart failure. These results suggest that pericyte detachment and PMT induced by increased RIHP are responsible for tubulointerstitial injury and fibrosis in DahlS rats and humans with renal congestion. Renal venous congestion and subsequent physiological changes could be therapeutic targets for renal damage in cardiorenal syndrome.
Topics: Humans; Rats; Animals; Rats, Inbred Dahl; Pericytes; Sodium Chloride; Kidney; Hypertension; Heart Failure; Sodium Chloride, Dietary; Fibrosis; Blood Pressure
PubMed: 37845397
DOI: 10.1038/s41440-023-01451-3