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Beilstein Journal of Nanotechnology 2024The mechanism by which insects achieve attachment and locomotion across diverse substrates has long intrigued scientists, prompting extensive research on the functional...
The mechanism by which insects achieve attachment and locomotion across diverse substrates has long intrigued scientists, prompting extensive research on the functional morphology of attachment pads. In stick insects, attachment and locomotion are facilitated by two distinct types of smooth cuticular attachment pads: the primary adhesion force-generating arolium and the friction force-generating euplantulae. They are both supported by an adhesive secretion delivered into the interspace between the attachment pads and the substrate. In this study, we analysed and compared internal morphology, material composition and ultrastructure, as well as the transportation pathways in both adhesive organs in the stick insect using scanning electron microscopy, micro-computed tomography, light microscopy, and confocal laser scanning microscopy. Our observations revealed structural differences between both attachment pads, reflecting their distinct functionality. Furthermore, our results delineate a potential pathway for adhesive secretions, originating from exocrine epidermal cells and traversing various layers before reaching the surface. Within the attachment pad, the fluid may influence the viscoelastic properties of the pad and control the attachment/detachment process. Understanding the material composition of attachment pads and the distribution process of the adhesive secretion can potentially aid in the development of more effective artificial attachment systems.
PubMed: 38887530
DOI: 10.3762/bjnano.15.52 -
BMC Ophthalmology Jun 2024
PubMed: 38886683
DOI: 10.1186/s12886-024-03525-3 -
PloS One 2024Photodynamic venous occlusion is a commonly accepted method for establishing mouse models of retinal vein occlusion (RVO). However, existing model parameters do not...
Photodynamic venous occlusion is a commonly accepted method for establishing mouse models of retinal vein occlusion (RVO). However, existing model parameters do not distinguish between acute and chronic RVO subtypes. Large variations in laser energy seem to correlate with fluctuating retinopathy severity and high rates of venous recanalization during the acute phase, along with the variable levels of retinal perfusion during the chronic phase. After optimizing the modeling procedure and defining success and exclusion criteria, laser energy groups of 80mW, 100mW, and 120mW were established. Multimodal imaging confirmed that higher energy levels increased the incidence of retinal cystoid edema and intraretinal hemorrhage, exacerbated the severity of exudative retinal detachment, and reduced the venous recanalization rate. For the acute model, 100mW was considered an appropriate parameter for balancing moderate retinopathy and venous recanalization. Continuous imaging follow-up revealed that day 1 after RVO was the optimal observation point for peaking of retinal thickness and intensive occurrence of retinal cystic edema and intraretinal hemorrhage. After excluding the influence of venous recanalization on retinal thickness, acute retinal edema demonstrated a positive response to standard anti-vascular endothelial growth factor therapy, validating the clinical relevance of the acute RVO model for further study in pathogenic mechanisms and therapeutic efficacy. For the chronic model, the 120mW parameter with the lowest venous recanalization rate was applied, accompanied by an increase in both photocoagulation shots and range to ensure sustained vein occlusion. Imaging follow-up clarified non-ischemic retinopathy characterized by tortuosity and dilation of the distal end, branches, and adjacent veins of the occluded vein. These morphological changes are quantifiable and could be combined with electrophysiological functional assessment for treatment effectiveness evaluation. Moreover, the stable state of venous occlusion may facilitate investigations into response and compensation mechanisms under conditions of chronic retinal hypoperfusion.
Topics: Retinal Vein Occlusion; Animals; Disease Models, Animal; Mice; Acute Disease; Chronic Disease; Lasers; Mice, Inbred C57BL; Male; Tomography, Optical Coherence; Retina
PubMed: 38885229
DOI: 10.1371/journal.pone.0305741 -
Journal of Pharmacy & Bioallied Sciences Apr 2024Descemet membrane endothelial keratoplasty (DMEK) has been utilized more frequently during recent years to treat penetrating keratoplasty (PKP) graft failures. The...
BACKGROUND
Descemet membrane endothelial keratoplasty (DMEK) has been utilized more frequently during recent years to treat penetrating keratoplasty (PKP) graft failures. The perioperative evaluation technique of anterior segment optical coherence tomography (AS-OCT) is increasingly significant. Our goal is to discuss DMEK surgical and clinical for subsequent PKP graft failure, along with significant surgical modifications and adjustments in accordance with preoperative assessment utilizing AS-OCT.
MATERIALS AND METHODS
Patients' records who performed DMEK for PKP failure were retrospectively reviewed. Demographic information, PKP graft size determined by postoperative problems, corneal donor endothelial cell density (ECD), AS-OCT, central pachymetry, visual acuity (VA) evaluated in Snellen units, intraoperative surgical procedure modifications, and postoperative ECD were all included in the data collection.
RESULTS
The observation was conducted with 16 patients with 16 eyes, nine males and seven females. The observation period is 18 months. DMEK was performed at an average age of 63. Preoperative AS-OCT was performed on all patients, and based on cases, surgical plans were created. Before processing DMEK, the mean VA is 0.04, and central pachymetry is 685 m. They improved considerably to 0.3 ( value = 0.001) and 542 m ( value = 0.008) at the most recent follow-up. About 93.75% of the grafts were adhered to after the procedure. Late decompensation caused a 6.25% graft failure rate. Graft detachment rates and cases requiring rebubble rates were respectively 18.75%.
CONCLUSION
In DMEK for failed PKP, a good case-specific preoperative assessment by AS-OCT is essential. As a result, it relies on developing a surgical strategy that can improve surgical outcomes, lower the risk of complications, and quicken visual recovery.
PubMed: 38882795
DOI: 10.4103/jpbs.jpbs_876_23 -
Journal of Pharmacy & Bioallied Sciences Apr 2024Matrix metalloproteinase-1 (MMP-1) plays a pivotal role in the pathogenesis of periodontal diseases, particularly periodontitis, by virtue of its collagenolytic activity... (Review)
Review
Matrix metalloproteinase-1 (MMP-1) plays a pivotal role in the pathogenesis of periodontal diseases, particularly periodontitis, by virtue of its collagenolytic activity targeting collagen type I, the primary component of periodontal tissues. This review abstract elucidates the intricate involvement of MMP-1 in periodontal tissue homeostasis and its dysregulation in disease states. Elevated MMP-1 levels, observed in gingival tissues and crevicular fluid of individuals with periodontitis, correlate with the degradation of collagen fibers within the periodontium. This degradation contributes to the detachment of teeth from surrounding tissues and exacerbates alveolar bone resorption, hallmark features of periodontal breakdown. Therapeutically, targeting MMP-1 activity emerges as a promising strategy, prompting ongoing research into MMP inhibitors and host modulation therapies. Understanding MMP-1's nuanced role in periodontal diseases paves the way for personalized treatment approaches and holds promise in reshaping periodontal disease management for improved patient outcomes and periodontal health.
PubMed: 38882751
DOI: 10.4103/jpbs.jpbs_1249_23 -
Ocular Oncology and Pathology Jun 2024Mitogen-activated protein kinase kinase (MEK) inhibitors are targeted anticancer agents that are prescribed to treat a broad range of cancers. Despite their strong...
INTRODUCTION
Mitogen-activated protein kinase kinase (MEK) inhibitors are targeted anticancer agents that are prescribed to treat a broad range of cancers. Despite their strong efficacy profile, MEK inhibitors have been associated with ocular toxicities, most notably, self-limited serous detachments of the neurosensory retina. In this report, we outline 3 cases of a rarely documented toxicity, MEK inhibitor-associated ocular hypertension.
CASE PRESENTATIONS
In the first case, a 69-year-old female with metastatic cholangiocarcinoma presented with an intraocular pressure (IOP) of 25 mm Hg right eye (OD) and 27 mm Hg left eye (OS) 2 months after starting trametinib therapy. Similarly, in the second case, a 26-year-old female with Langerhans cell histiocytosis presented with an elevated IOP of 24 mm Hg bilaterally (OU) 13 months after beginning treatment with an investigational MEK inhibitor. In the third case, a 46-year-old male with Langerhans cell histiocytosis presented with a new onset of elevated IOP of 24 mm Hg 21 days after initiating treatment with cobimetinib. All 3 patients' IOP returned to normal following dorzolamide/timolol administration and continued their cancer therapy.
DISCUSSION/CONCLUSION
This report presents 3 cases of elevated IOP in patients taking three distinct MEK inhibitors which would suggest that IOP-elevating effects exist across the class of MEK inhibitors. All 3 patients had a satisfactory response to topical pressure-lowering drops while continuing their life-preserving MEK inhibitor drug dose, indicating that discontinuation of therapy may not be necessary. Due to the increasing use of MEK inhibitors, it is important that ophthalmologists familiarize themselves with the broad range of potential adverse ocular effects of MEK inhibitors.
PubMed: 38882021
DOI: 10.1159/000535427 -
Ophthalmology Science 2024To determine the clinical characteristics of familial exudative vitreoretinopathy (FEVR) associated with or without pathogenic variants of the Norrin/β-catenin genes.
PURPOSE
To determine the clinical characteristics of familial exudative vitreoretinopathy (FEVR) associated with or without pathogenic variants of the Norrin/β-catenin genes.
DESIGN
This was a multicenter, cross-sectional, observational, and genetic study.
SUBJECTS
Two-hundred eighty-one probands with FEVR were studied.
METHODS
Whole-exome sequence and/or Sanger sequence was performed for the Norrin/β-catenin genes, the , , , and genes on blood collected from the probands. The clinical symptoms of the probands with or without the pathogenic variants were assessed as well as differences in the inter Norrin/β-catenin genes.
MAIN OUTCOME MEASURES
The phenotype associated with or without pathogenic variants of the Norrin/β-catenin genes.
RESULTS
One-hundred eight probands (38.4%) had 88 different pathogenic or likely pathogenic variants in the genes: 24 with the , 42 with the , 10 with the , and 12 with the gene. Compared with the 173 probands without pathogenic variants, the 108 variant-positive probands had characteristics of familial predisposition (63.9% vs. 37.6%, < 0.0001), progression during infancy (75.0% vs. 53.8%, = 0.0004), asymmetrical severity between the 2 eyes (50.0% vs. 37.6%, = 0.0472), and nonsyndromic characteristics (10.2% vs. 17.3%, = 0.1185). The most frequent stage at which the more severe eye conditions was present was at stage 4 in both groups (40.7% vs. 34.7%). However, the advanced stages of 3 to 5 in the more severe eye were found more frequently in probands with variants than in those without variants (83.3% vs. 58.4%, < 0.0001). Patients with rhegmatogenous retinal detachments progressed from stage 1 or 2 were found less frequently in the variant-positive probands (8.3% vs. 17.3%, = 0.0346). Nine probands with variants had features different from probands with typical Norrin/β-catenin gene variants including the sporadic, symmetrical, and systemic characteristics consistent with Norrie disease.
CONCLUSIONS
The results showed that the clinical characteristics of FEVR of patients with variants in the Norrin/β-catenin genes are different from those with other etiologies. We recommend that clinicians who diagnose a child with FEVR perform genetic testing so that the parents can be informed on the prognosis of the vision and general health in the child.
FINANCIAL DISCLOSURES
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
PubMed: 38881609
DOI: 10.1016/j.xops.2024.100514 -
Endocrine Journal Jun 2024The endometrium during the sexual cycle undergoes detachment, tissue remodeling, and differentiation during the menstrual cycle. Localized and transient destruction and...
The endometrium during the sexual cycle undergoes detachment, tissue remodeling, and differentiation during the menstrual cycle. Localized and transient destruction and regeneration of endometrial tissue are also essential for pregnancy. It is possible to attribute many causes of failure in infertility treatment to the implantation stage. To improve the success rate of plateau fertility treatment, it is important to understand the regeneration mechanism of the endometrium, a unique regenerative tissue in the human body. In association with cell proliferation, tissue remodeling requires the relocation of proliferative cells, and the steady-state epithelial cells need to be motile for the relocation. Transient add-on motile activity in epithelial cells is mediated by epithelial to mesenchymal transition (EMT) and reversible mesenchymal to epithelial transition (MET). The destruction and regeneration of endometrial tissue over a period of days to weeks requires a system with a rapid and characteristic mechanism similar to that of wound healing. Here, I review the relationship between the well-known phenomenon of EMT in wound healing and endometrial tissue remodeling during the sexual cycle and pregnancy establishment, which are automatically triggered by menstruation and embryonal invasion.
PubMed: 38880606
DOI: 10.1507/endocrj.EJ24-0229 -
Journal of Lipid Research Jun 2024Apolipoprotein AV (APOA5) deficiency causes hypertriglyceridemia in mice and humans. For years, the cause remained a mystery, but the mechanisms have now come into... (Review)
Review
Apolipoprotein AV (APOA5) deficiency causes hypertriglyceridemia in mice and humans. For years, the cause remained a mystery, but the mechanisms have now come into focus. Here, we review progress in defining APOA5's function in plasma triglyceride metabolism. Biochemical studies revealed that APOA5 binds to the angiopoietin-like protein 3/8 complex (ANGPTL3/8) and suppresses its ability to inhibit the activity of lipoprotein lipase (LPL). Thus, APOA5 deficiency is accompanied by increased ANGPTL3/8 activity and lower levels of LPL activity. APOA5 deficiency also reduces amounts of LPL in capillaries of oxidative tissues (e.g., heart, brown adipose tissue). Cell culture experiments revealed the likely explanation: ANGPTL3/8 detaches LPL from its binding sites on the surface of cells, and that effect is blocked by APOA5. Both the low intracapillary LPL levels and the high plasma triglyceride levels in Apoa5 mice are normalized by recombinant APOA5. Carboxyl-terminal sequences in APOA5 are crucial for its function; a mutant APOA5 lacking 40-carboxyl-terminal residues cannot bind to ANGPTL3/8 and lacks the ability to change intracapillary LPL levels or plasma triglyceride levels in Apoa5 mice. Also, an antibody against the last 26 amino acids of APOA5 reduces intracapillary LPL levels and increases plasma triglyceride levels in wild-type mice. An inhibitory ANGPTL3/8-specific antibody functions as an APOA5-mimetic reagent, increasing intracapillary LPL levels and lowering plasma triglyceride levels in both Apoa5 and wild-type mice. That antibody is a potentially attractive strategy for treating elevated plasma lipid levels in human patients.
PubMed: 38880127
DOI: 10.1016/j.jlr.2024.100578 -
Journal of Neuroscience Methods Jun 2024Ependymal cilia play a major role in the circulation of cerebrospinal fluid. Although isolation of cilia is an essential technique for investigating ciliary structure,...
BACKGROUND
Ependymal cilia play a major role in the circulation of cerebrospinal fluid. Although isolation of cilia is an essential technique for investigating ciliary structure, to the best of our knowledge, no report on the isolation and structural analysis of ependymal cilia from mouse brain is available.
NEW METHOD
We developed a novel method for isolating ependymal cilia from mouse brain ventricles. We isolated ependymal cilia by partially opening the lateral ventricles and gently applying shear stress, followed by pipetting and ultracentrifugation.
RESULTS
Using this new method, we were able to observe cilia separately. The results demonstrated that our method successfully isolated intact ependymal cilia with preserved morphology and ultrastructure. In this procedure, the ventricular ependymal cell layer was partially detached.
COMPARISON WITH EXISTING METHODS
Compared to existing methods for isolating cilia from other tissues, our method is meticulously tailored for extracting ependymal cilia from the mouse brain. Designed with a keen understanding of the fragility of the ventricular ependyma, our method prioritizes minimizing tissue damage during the isolation procedure.
CONCLUSIONS
We isolated ependymal cilia from mouse brain by applying shear stress selectively to the ventricles. Our method can be used to conduct more detailed studies on the structure of ependymal cilia.
PubMed: 38878975
DOI: 10.1016/j.jneumeth.2024.110198