ABSTRACT
To investigate the correlations between finger microvascular morphology and function in patients with systemic sclerosis (SSc) and the status of ocular microcirculation, as detected by nailfold videocapillaroscopy (NVC), laser speckle contrast analysis (LASCA), and optical coherence tomography angiography (OCTA). The enrollment included 32 SSc patients, classified according to the 2013 ACR/EULAR criteria, and 27 sex- and age-matched healthy controls. The participants underwent comprehensive rheumatological and ophthalmological examinations, as well as NVC, LASCA, and OCTA analysis on the same day at a single center from March to October 2022. SSc patients receiving intravenous prostanoids cycles were assessed at least 1 month after infusion. Statistical analysis was conducted using Stata® 15.1. Significant direct correlations were observed between the mean capillary number (at NVC) and the mean perfusion of fingers (at LASCA) with the retinal and choroidal perfusion (at OCTA) (all p < 0.05). In addition, a significantly reduced retinal and choroidal perfusion was detected in SSc patients vs controls (all p < 0.05). Interestingly, diffuse cutaneous SSc (dcSSc) patients exhibited a lower choroidal perfusion (p = 0.03) but an increased choroidal thickness (CT) than limited cutaneous SSc patients (p < 0.001). CT was increased also in patients with positive Scl70 antibodies and with a history of digital ulcers directly correlating with disease duration (r = 0.67, p = 0.001). Finally, the combination of LASCA and OCTA parameters showed a significant discrimination capacity between SSc patients and controls, with an area under the curve of 0.80 [95% CI (0.74, 0.87)]. Peripheral microvascular damage is correlated with impaired ocular microcirculation in SSc. The increased choroidal thickness observed in dcSSc may be related to local sub-endothelial extracellular matrix deposition. The combined analysis of choroidal and fingertip perfusion offers preliminary insights that may complement traditional diagnostic methods for SSc.
Subject(s)
Microscopic Angioscopy , Scleroderma, Systemic , Humans , Tomography, Optical Coherence , Perfusion , AngiographyABSTRACT
The widespread use of nanoparticles (NPs) in medical devices has opened a new scenario in the treatment and prevention of many diseases and infections owing to unique physico-chemical properties of NPs. In this way, silver nanoparticles (AgNPs) are known to have a strong antimicrobial activity, even at low concentrations, due to their ability to selectively destroy cellular membranes. In particular, in the field of dental medicine, the use of AgNPs in different kinds of dental prosthesis matrixes could be a fundamental tool in immunodepressed patients that suffer of different oral infections. Candida albicans (C. albicans), an opportunistic pathogenic yeast with high colonization ability, is one of the causative agents of oral cavity infection. In our work, we added monodispersed citrate-capping AgNPs with a size of 20 nm at two concentrations (3 wt% and 3.5 wt%) in poly(methyl methacrylate) (PMMA), the common resin used to develop dental prostheses. After AgNPs characterization, we evaluated the topographical modification of PMMA and PMMA with the addition of AgNPs by means of atomic force microscopy (AFM), showing the reduction of surface roughness. The C. albicans colonization on PMMA surfaces was assessed by the Miles and Misra technique as well as by scanning electron microscopy (SEM) at 24 h and 48 h with encouraging results on the reduction of yeast viability after AgNPs exposure.
Subject(s)
Antifungal Agents/pharmacology , Dental Prosthesis/microbiology , Metal Nanoparticles/chemistry , Polymethyl Methacrylate/chemistry , Silver/pharmacology , Antifungal Agents/chemistry , Candida albicans/drug effects , Candida albicans/ultrastructure , Humans , Metal Nanoparticles/ultrastructure , Microscopy, Atomic Force , Microscopy, Electron, Scanning , Silver/chemistryABSTRACT
Alginate (ALG) and chitosan (CS) have been extensively used for biomedical applications; however, data relative to immune responses exerted by them are scarce. We synthesized a submicron vesicle system (SV) displaying a CS shell over an ALG core. Intravenous injection of these promising carriers could be a possible route of delivery; therefore, we evaluated their impact on human peripheral blood mononuclear cells (PBMCs). By this ex vivo approach, we established how SV chemical-physical characteristics affected the immune cells in terms of cellular uptake, viability, and state of activation. By flow cytometry, we demonstrated that SVs were internalized by PBMCs with differential trends. No substantial necrotic and apoptotic signals were recorded, and SVs weakly affected activation status of PBMCs (concerning the markers CD69, CD25, CD80, and the cytokines TNF-α and IL-6), showing high immune biocompatibility and low immunomodulating properties. Our findings gain particular value toward the biomedical applications of SVs and make these polymer-based structures more attractive for translation into clinical uses.
Subject(s)
Alginates/chemistry , Chitosan/analogs & derivatives , Monocytes/drug effects , Nanoparticles/adverse effects , Adult , Antigens, CD/immunology , Apoptosis , Cells, Cultured , Chitosan/immunology , Humans , Interleukin-6/immunology , Middle Aged , Monocytes/immunology , Nanoparticles/chemistry , Tumor Necrosis Factor-alpha/immunologyABSTRACT
The EMT phenomenon is based on tumour progression. The cells lose their physiologic phenotype and assumed a mesenchymal phenotype characterized by an increased migratory capacity, invasiveness and high resistance to apoptosis. In this process, RHO family regulates the activation or suppression of ROCK (Rho-associated coiled-coil containing protein kinase) which in turn regulates the cytoskeleton dynamics. However, while the biochemical mechanisms are widely investigated, a comprehensive and careful estimation of biomechanical changes has not been extensively addressed. In this work, we used a strong ROCK inhibitor, Y-27632, to evaluate the effects of inhibition on living breast cancer epithelial cells by a biomechanical approach. Atomic Force Microscopy (AFM) was used to estimate changes of cellular elasticity, quantified by Young's modulus parameter. The morphometric alterations were analyzed by AFM topographies and Confocal Laser Scanning Microscopy (CLSM). Our study revealed a significant modification in the Young's modulus after treatment, especially as regards cytoskeletal region. Our evidences suggest that the use of Y-27632 enhanced the cell rigidity, preventing cell migration and arrested the metastasization process representing a potential powerful factor for cancer treatment.
Subject(s)
Amides/pharmacology , Breast Neoplasms/pathology , Breast Neoplasms/ultrastructure , Cell Shape/drug effects , Pyridines/pharmacology , rho-Associated Kinases/antagonists & inhibitors , Cell Adhesion/drug effects , Cell Movement/drug effects , Cytoskeleton/drug effects , Cytoskeleton/metabolism , Cytoskeleton/ultrastructure , Elastic Modulus/drug effects , Elasticity/drug effects , Female , Humans , MCF-7 Cells , Microscopy, Atomic Force , Stress, Mechanical , Tumor Cells, CulturedABSTRACT
PURPOSE: This study aimed to describe a rare case of bilateral choroidal effusion following a XEN45 implantation. CASE REPORT: An 84-year-old man with primary open-angle glaucoma underwent uneventful ab interno XEN45 device implantation in the right eye. The immediate postoperative period was complicated by hypotony and serous choroidal detachment, which were treated and resolved using steroids and cycloplegic drops. Eight months later, the fellow eye underwent the same surgery, which was followed by choroidal detachment that required transscleral surgical drainage. CONCLUSIONS: This case highlights the importance of a careful postoperative follow-up and a timely intervention in the context of XEN45 implantation, and suggests that choroidal effusion in one eye may be a risk factor for choroidal effusion in the other eye when undergoing the same type of surgery.
ABSTRACT
We present the case of a 61-year-old man who reported diplopia due to a right abducens nerve palsy. The patient complained of fever every night (37.5° C), paresthesia of the second and third hand fingers, and he showed an increased C-reactive protein, high erythrocyte sedimentation rate, and high eosinophilia. He had a history of allergic asthma, chronic rhinosinusitis, and surgically treated nasal polyps. His past medical history and labs led us to identify the eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg-Strauss syndrome. EGPA is a potentially life-threatening condition, and a proper diagnosis was critical to managing this patient's abducens nerve palsy.
Subject(s)
Abducens Nerve Diseases , Asthma , Churg-Strauss Syndrome , Granulomatosis with Polyangiitis , Sinusitis , Male , Humans , Middle Aged , Churg-Strauss Syndrome/complications , Churg-Strauss Syndrome/diagnosis , Granulomatosis with Polyangiitis/complications , Granulomatosis with Polyangiitis/diagnosis , Asthma/complications , Sinusitis/complications , Sinusitis/diagnosis , Abducens Nerve Diseases/diagnosis , Abducens Nerve Diseases/etiologyABSTRACT
The current strategies to treat different kinds of cancer are mainly based on chemotherapy, surgery and radiation therapy. Unfortunately, these approaches are not specific and rather invasive as well. In this scenario, metal nano-shells, in particular gold-based nanoshells, offer interesting perspectives in the effort to counteract tumor cells, due to their unique ability to tune Surface Plasmon Resonance in different light-absorbing ranges. In particular, the Visible and Near Infrared Regions of the electromagnetic spectrum are able to penetrate through tissues. In this way, the light absorbed by the gold nanoshell at a specific wavelength is converted into heat, inducing photothermal ablation in treated cancer cells. Furthermore, inert gold shells can be easily functionalized with different types of molecules in order to bind cellular targets in a selective manner. This review summarizes the current state-of-art of nanosystems embodying gold shells, regarding methods of synthesis, bio-conjugations, bio-distribution, imaging and photothermal effects (in vitro and in vivo), providing new insights for the development of multifunctional antitumor drugs.
Subject(s)
Gold , Hyperthermia, Induced , Nanoshells , Neoplasms/therapy , Phototherapy , Cell Line, Tumor , Humans , Surface Plasmon ResonanceABSTRACT
The nowadays growing use of nanoparticles (NPs) in commercial products does not match a comprehensive understanding of their potential harmfulness. More in vitro investigations are required to address how the physicochemical properties of NPs guide their engulfment within cells and their intracellular trafficking, fate, and toxicity. These nano-bio interactions have not been extensively addressed yet, especially from a mechanical viewpoint. Cell mechanic is a critical indicator of cell health because it regulates processes like cell migration, tissue integrity, and differentiation via cytoskeleton rearrangements. Here, we investigated in vitro the elasticity perturbation of Caco-2 and A549 cell lines, in terms of Young's modulus modification induced by SiO2NPS and TiO2NPS. TiO2NPs demonstrated stronger effects on cell elasticity compared to SiO2NPs, as they induced significant morphological and morphometric changes in actin network. TiO2NPS increased the elasticity in Caco-2 cells, while opposite effects have been observed on A549 cells. These results demonstrate the existence of a correlation between the alteration of cell elasticity and NPs toxicity that depends, in turn, on the NPs physicochemical properties and the specific cell tested.
ABSTRACT
The Epithelial to mesenchymal transition (EMT) is the process that drives epithelial tumor cells to acquire an invasive phenotype. The role of transforming growth factor-ß1 (TGF-ß1) in EMT is still debated. We used confocal laser scanning microscopy and scanning force spectroscopy to perform a morphomechanical analysis on epithelial breast cancer cells (MCF-7), comparing them before and after TGF-ß1 exogenous stimulation (5 ng/mL for 48 h). After TGF-ß1 treatment, loss of cellâ»cell adherence (mainly due to the reduction of E-cadherin expression of about 24%) and disaggregation of actin cortical fibers were observed in treated MCF-7. In addition, TGF-ß1 induced an alteration of MCF-7 nuclei morphology as well as a decrease in the Young's modulus, owing to a rearrangement that involved the cytoskeletal networks and the nuclear region. These relevant variations in morphological features and mechanical properties, elicited by TGF-ß1, suggested an increased capacity of MCF-7 to migrate, which was confirmed by a wound healing assay. By means of our biophysical approach, we highlighted the malignant progression of breast cancer cells induced by TGF-ß1 exposure. We are confirming TGF-ß1's role in EMT by means of morphomechanical evidence that could represent a turning point in understanding the molecular mechanisms involved in cancer progression.
ABSTRACT
The large use of nanomaterials in many fields of application and commercial products highlights their potential toxicity on living organisms and the environment, despite their physico-chemical properties. Among these, silver nanoparticles (Ag NPs) are involved in biomedical applications such as antibacterial agents, drug delivery vectors and theranostics agents. In this review, we explain the common synthesis routes of Ag NPs using physical, chemical, and biological methods, following their toxicity mechanism in cells. In particular, we analyzed the physiological cellular pathway perturbations in terms of oxidative stress induction, mitochondrial membrane potential alteration, cell death, apoptosis, DNA damage and cytokines secretion after Ag NPs exposure. In addition, their potential anti-cancer activity and theranostic applications are discussed.
ABSTRACT
Acute kidney injury (AKI) is a public health problem worldwide. Several therapeutic strategies have been made to accelerate recovery and improve renal survival. Recent studies have shown that human adult renal progenitor cells (ARPCs) participate in kidney repair processes, and may be used as a possible treatment to promote regeneration in acute kidney injury. Here, we show that human tubular ARPCs (tARPCs) protect physically injured or chemically damaged renal proximal tubular epithelial cells (RPTECs) by preventing cisplatin-induced apoptosis and enhancing proliferation of survived cells. tARPCs without toll-like receptor 2 (TLR2) expression or TLR2 blocking completely abrogated this regenerative effect. Only tARPCs, and not glomerular ARPCs, were able to induce tubular cell regeneration process and it occurred only after damage detection. Moreover, we have found that ARPCs secreted inhibin-A and decorin following the RPTEC damage and that these secreted factors were directly involved in cell regeneration process. Polysaccharide synthetic vesicles containing these molecules were constructed and co-cultured with cisplatin damaged RPTECs. These synthetic vesicles were not only incorporated into the cells, but they were also able to induce a substantial increase in cell number and viability. The findings of this study increase the knowledge of renal repair processes and may be the first step in the development of new specific therapeutic strategies for renal repair.
Subject(s)
Adult Stem Cells/metabolism , Decorin/biosynthesis , Epithelial Cells/metabolism , Inhibins/biosynthesis , Kidney Tubules/metabolism , Regeneration , Toll-Like Receptor 2/metabolism , Acute Kidney Injury/etiology , Acute Kidney Injury/metabolism , Adult , Adult Stem Cells/drug effects , Apoptosis/drug effects , Biomarkers , Cell Differentiation , Cell Proliferation/drug effects , Cells, Cultured , Cisplatin/pharmacology , Epithelial Cells/cytology , Epithelial Cells/drug effects , HumansABSTRACT
Titanium dioxide nanoparticles (TiO2NPs), in the two crystalline forms, rutile and anatase, have been widely used in many industrial fields, especially in cosmetics. Therefore, a lot of details about their safety issues have been discussed by the scientific community. Many studies have led to a general agreement about TiO2NPs toxicity, in particular for anatase form, but no mechanism details have been proved yet. In this study, data confirm the different toxic potential of rutile and anatase TiO2NPs in two cell lines up to 5nM nanoparticles concentration. Moreover, we evaluated the role of titanium ions released by TiO2NPs in different conditions, at pH=4.5 (the typical lysosomal compartment pH) and at pH=5.5 (the skin physiological pH) in conditions of darkness and light, to mimic the dermal exposure of cosmetics. Anatase nanoparticles were proner to degradation both in the acidic conditions and at skin pH. Our study demonstrates that pH and sunlight are dominant factors to induce oxidative stress, TiO2NPs degradation and toxicity effects.