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1.
Graphene and other 2D materials: a multidisciplinary analysis to uncover the hidden potential as cancer theranostics.
Fusco, L, Gazzi, A, Peng, G, Shin, Y, Vranic, S, Bedognetti, D, Vitale, F, Yilmazer, A, Feng, X, Fadeel, B, et al
Theranostics. 2020;(12):5435-5488
Abstract
Cancer represents one of the main causes of death in the world; hence the development of more specific approaches for its diagnosis and treatment is urgently needed in clinical practice. Here we aim at providing a comprehensive review on the use of 2-dimensional materials (2DMs) in cancer theranostics. In particular, we focus on graphene-related materials (GRMs), graphene hybrids, and graphdiyne (GDY), as well as other emerging 2DMs, such as MXene, tungsten disulfide (WS2), molybdenum disulfide (MoS2), hexagonal boron nitride (h-BN), black phosphorus (BP), silicene, antimonene (AM), germanene, biotite (black mica), metal organic frameworks (MOFs), and others. The results reported in the scientific literature in the last ten years (>200 papers) are dissected here with respect to the wide variety of combinations of imaging methodologies and therapeutic approaches, including drug/gene delivery, photothermal/photodynamic therapy, sonodynamic therapy, and immunotherapy. We provide a unique multidisciplinary approach in discussing the literature, which also includes a detailed section on the characterization methods used to analyze the material properties, highlighting the merits and limitations of the different approaches. The aim of this review is to show the strong potential of 2DMs for use as cancer theranostics, as well as to highlight issues that prevent the clinical translation of these materials. Overall, we hope to shed light on the hidden potential of the vast panorama of new and emerging 2DMs as clinical cancer theranostics.
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2.
Biomechanical effect of ultraviolet-A-riboflavin cross-linking on simulated human corneal stroma model and its correlation with changes in corneal stromal microstructure.
Li, H, Liu, T, Mu, B, Zhao, X, Xue, C, Shen, M, Jhanji, V, Wang, Y
Experimental eye research. 2020;:108109
Abstract
In this study, we established an experimental human corneal stroma model of simulated cornea tissue composed of thin anterior cornea strips layers obtained from small incision lenticular extraction (SMILE) surgery. We investigated the biomechanical effect of ultraviolet-A- riboflavin cross-linking at different depths of corneal stroma model and correlated it with stromal microstructural changes examined by transmission electron microscopy (TEM). Corneal strips were harvested from fresh human corneal lenticules obtained after SMILE surgery. Experimental models (n = 34) were established by superimposing the corneal lenticule strips until their thickness reached close to 500 μm. Corneal cross-linking (CXL) was performed subsequently using standard or accelerated protocol. Elasticity and viscosity were quantified using stress-strain extensometer. TEM was used to visualize the collagen fiber diameter and interfibrillar spacing. The relative change in Young's modulus (rel. ΔE) decreased nonlinearly with increasing stromal depth both in the standard and accelerated groups. Compared to the sham controls, the rel. ΔE in standard and accelerated CXL groups increased significantly in the anterior 400 μm and 275 μm depth, respectively. Also, the relative change in stress (rel. ΔS) was significantly lower after standard and accelerated CXL compared to sham controls. Depth analysis showed similar results for the elastic effect. TEM images showed a small, non-significant increase in fibril diameter. The interfibrillar spacing decreased significantly after standard and accelerated CXL in the anterior-mid stromal region. We noted that the increase of corneal stiffness correlated with decrease in interfibrillar spacing after CXL. The stiffening effect was depth dependent. The effect of accelerated CXL was less in the deep corneal stromal regions compared to standard CXL.
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Corneal refractive surgery combined with simultaneous corneal cross-linking: Indications, protocols and clinical outcomes-A review.
Ma, J, Wang, Y, Jhanji, V
Clinical & experimental ophthalmology. 2020;(1):78-88
Abstract
Corneal refractive surgery is one of the most common approaches for correction of refractive errors. Combined corneal refractive surgery and corneal cross-linking (CXL) has been proposed as a method to achieve better refractive stability and to prevent iatrogenic corneal ectasia. However, there are concerns regarding its indications, surgical safety, standardization of protocols and long-term effect on corneal tissue. This review article aims to discuss the current knowledge and recent updates on combination of CXL and refractive surgery.
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4.
Tear function and ocular surface changes following corneal collagen cross-linking treatment in keratoconus patients: 18-month results.
Uysal, BS, Akcay, E, Kilicarslan, A, Mutlu, M, Hondur, G, Kosekahya, P, Cagil, N
International ophthalmology. 2020;(1):169-177
Abstract
PURPOSE To investigate the long-term effects that CXL has on the tear function and ocular surface in keratoconus. METHODS Twenty-one consecutive patients (24 eyes) with progressive keratoconus scheduled for CXL were included. All patients underwent the following procedures: conjunctival impression cytology analysis, ocular surface disease index (OSDI) score, tear osmolarity test, Schirmer test, tear film breakup time (TBUT), ophthalmic surface fluorescein (Fl) staining, and topographical corneal evaluation before as well as 3 and 18 months after accelerated CXL. RESULTS There was no change in the median OSDI score, tear osmolarity test, Schirmer test, and the Fl staining score after CXL. The median TBUT increased from 9.00 s at baseline to 12.00 s at 18 months postoperative (P < 0.001). The cytological features of the temporal and superior bulbar conjunctiva deteriorated at 3 months post-CXL (P < 0.001). An improvement in impression cytology analysis of the temporal conjunctiva was noted at 18-month follow-up (P < 0.001). Significant improvements in the median maximum keratometry and mean keratometry (K-mean) readings were also noted 18 months after CXL (P < 0.001). The changes in the K-mean correlated significantly with the changes in TBUT levels at 18-month follow-up as compared to baseline (r = - 0.688, P < 0.001). CONCLUSIONS The improvement in TBUT, conjunctival squamous metaplasia, and the goblet cell density indicates a favorable effect of CXL on the ocular surface and tear film in keratoconus, presumably due to the reduced corneal irregularity after CXL.
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Comparison of Femto-LASIK With Combined Accelerated Cross-linking to Femto-LASIK in High Myopic Eyes: A Prospective Randomized Trial.
Kohnen, T, Lwowski, C, Hemkeppler, E, de'Lorenzo, N, Petermann, K, Forster, R, Herzog, M, Böhm, M
American journal of ophthalmology. 2020;:42-55
Abstract
PURPOSE To evaluate the safety and efficacy of femtosecond (fs) laser-assisted in situ keratomileusis (LASIK) combined with accelerated corneal cross-linking (LASIK Xtra) compared to conventional fs-LASIK (convLASIK) in high myopic patients. DESIGN Prospective, randomized, fellow-eye controlled clinical trial. METHODS Setting: Department of Ophthalmology, Goethe University, Frankfurt/Germany. StudyPopulation: Twenty-six patients with high myopia and/or myopic astigmatism received randomized treatment with LASIK Xtra (30 mW/cm2, 90 seconds with continuous ultraviolet-A) in 1 eye and convLASIK in the other eye. MainOutcomeMeasures: Uncorrected distance visual acuity (UDVA), best spectacle-corrected VA (BSCVA), manifest refractive spherical equivalent (MRSE), endothelial cell count (ECC), and corneal thickness. RESULTS The UDVA improved from 1.26 ± 0.13 logMAR preoperative to -0.02 ± 0.15logMAR in LASIK Xtra eyes and from 1.27 ± 0.12 logMAR to 0.01 ± 0.15 logMAR in the convLASIK eyes (P > .05). The MRSE changed from -7.35 ± 1.15 diopters (D) and -7.5 ± 1.12 D to -0.17 ± 0.43 D and -0.25 ± 0.46 D, respectively. There was no significant difference in outcomes between both groups during the 12 months follow-up except for the convLASIK eyes' showing slightly better BSCVA after 1 week (P < .05). ConvLASIK eyes revealed a nonsignificant trend toward myopic regression from 3 to 12 months postoperative with a change in MRSE of -0.15 D compared to -0.1 D in LASIK Xtra eyes. Topography showed stability of corneal curvature with no signs of keratectasia in both groups at 12 months. CONCLUSION While apparently safe, LASIK Xtra showed no advantages over conventional LASIK. At 12 months, both groups showed no difference regarding UDVA and refractive stability, and no signs of keratectasia.
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6.
Antimicrobial photodynamic therapy effectiveness against susceptible and methicillin-resistant Staphylococcus aureus biofilms.
Teixeira, CGS, Sanitá, PV, Ribeiro, APD, Dias, LM, Jorge, JH, Pavarina, AC
Photodiagnosis and photodynamic therapy. 2020;:101760
Abstract
BACKGROUND Staphylococcus aureus have a great ability to become rapidly resistant to conventional antimicrobial therapies. This study evaluated the efficacy of antimicrobial photodynamic therapy (aPDT) mediated by Curcumin (Cur) and light-emitting diode (LED) in the inactivation of biofilms of methicillin susceptible and resistant S. aureus (MSSA and MRSA, respectively). METHODS Biofilms were treated with Cur (20, 40 or 80 μM) and illuminated with LED source (455 ± 3 nm; 5.28 J/cm2) (aPDT groups), or treated either with Cur or LED only. Other samples were not exposed to Cur or LED (negative control). The biofilms viability after all experimental conditions were evaluated by counting the number of colonies (CFU/mL) and XTT assay. Additional samples were also evaluated by LIVE/DEAD® staining using confocal laser scanning microscopy (CLSM). Data were analyzed by ANOVAs followed by the Games-Howell post hoc test (α = 0.05). RESULTS For both strains, all aPDT groups significantly reduced both CFU/mL and metabolic activity of biofilms compared to the negative control (p < 0.001). The results were enhanced when 80 μM of Cur was used. CLSM images showed that both bacteria biofilms submitted to aPDT had a large number of red-stained colonies, especially at aPDT80. In general, MRSA biofilms tended to be less susceptible to aPDT than MSSA biofilms. CONCLUSIONS It can be concluded that aPDT mediated by Cur and LED was an efficient method to inactivate 48 -h biofilms of both S. aureus strains.
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Total mouth photodynamic therapy mediated by blue led and curcumin in individuals with AIDS.
Cristina Da Silva, F, Rosa, LP, Santos, GPO, Inada, NM, Blanco, KC, Araújo, TSD, Bagnato, VS
Expert review of anti-infective therapy. 2020;(7):689-696
Abstract
OBJECTIVES To test the effectiveness of an efficient therapeutic protocol for the total mouth antimicrobial photodynamic therapy (aPDT) mediated by 450 nm blue LED associated with curcumin in individuals with AIDS. METHODS Patients were selected by exclusion criteria and randomly distributed in groups to test the effectiveness of antimicrobial aPDT with curcumin 0.75 mg/mL associated with the blue LED (67 mW/cm2, 20.1 J/cm2). Before and after the treatments, samples were collected from the saliva being processed in duplicate in selective culture media. The colonies were counted and the results obtained in log10 CFU/mL were statistically tested (T-paired statistical test, 5%). RESULTS The log10 CFU/mL of Streptococcus spp., Staphylococcus spp., and total count of microorganisms showed statistically significant (p = 0.023; p = 0.001 and p = 0.017, respectively) reduction after treatment in patients with aPDT. CONCLUSION aPDT was effective in reducing Streptococcusspp. in addition to reducing Staphylococcusspp., enterobacteria and the total count of microorganisms when considering the numbers of TCD4 and TCD8 lymphocytes. The aPDT in the studied protocol was able to control clinically important intraoral microorganisms for AIDS patients, both those with TCD4 lymphocytes above or below 25% of normal and those with TCD8 lymphocytes above 25% of normal.
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8.
Modulation of Extracellular Matrix Rigidity Via Riboflavin-mediated Photocrosslinking Regulates Invasive Motility and Treatment Response in a 3D Pancreatic Tumor Model.
Jafari, R, Cramer, GM, Celli, JP
Photochemistry and photobiology. 2020;(2):365-372
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Abstract
In this study, we evaluate the use of riboflavin-mediated collagen photocrosslinking as an experimental tool to modulate extracellular matrix (ECM) mechanical properties in 3D in vitro tumor models. Using this approach in conjunction with 3D pancreatic tumor spheroid transplants, we show that the extent of matrix photocrosslinking in reconstituted hydrogels with fixed protein concentration scales inversely with the extent of invasive progression achieved by cells infiltrating into the surrounding ECM from primary transplanted spheroids. Using cross-linking to manipulate the extent of invasion into ECM in conjunction with imaging-based treatment assessment, we further leverage this approach as a means for assaying differential therapeutic response in primary nodule and ECM-invading populations and compare response to verteporfin-based photodynamic therapy (PDT) and oxaliplatin chemotherapy. Treatment response data shows that invading cell populations (which also exhibit markers of increased EMT) are highly chemoresistant yet have significantly increased sensitivity to PDT relative to the primary nodule. In contrast, the oxaliplatin treatment achieves greater growth inhibition of the primary nodule. These findings may be significant in themselves, while the methodology developed here could have a broader range of applications in developing strategies to target invasive disease and/or mecahanobiological determinants of therapeutic response in solid tumors.
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Topical treatment with oleocanthal extract in reducing inflammatory reactions after photodynamic therapy: a prospective quasi-experimental pilot study.
Segura Palacios, JM, Blázquez Sánchez, N, Rivas Ruiz, F, Aguilar Bernier, M, Ramírez López, B, Sánchez, MEF, de Troya Martín, M
Complementary therapies in medicine. 2019;:298-301
Abstract
OBJECTIVE Photodynamic therapy (PDT) is an effective treatment against skin field cancerization. Its main side effect is local inflammation in the treated area. The phenolic compound oleocanthal (decarboxy methyl ligstroside aglycone), which is present in extra virgin olive oil (EVOO), has anti-inflammatory properties. The purpose of this study was to evaluate the topical efficacy of an oily fluid enriched with oleocanthal (OC) extract, in comparison with a conventional oily fluid, in reducing the degree of inflammatory reaction after conventional PDT. METHODS Quasi-experimental pilot study, before-after with a control group, performed with a cohort of consecutive patients diagnosed with actinic keratosis/field cancerization (AK/FC) in the forehead and/or scalp, treated by PDT. The study was carried out from April 2016 to November 2017 at a speciality hospital in southern Spain. A group of 24 consecutive patients received the topical application, three times daily for one week, of an emollient oily fluid in the area treated with PDT. Subsequently, another group, of 23 consecutive patients, received the same treatment pattern with an oily fluid enriched with OC extract. The post-PDT inflammatory reaction was measured by an independent member of the hospital's dermatology department, using the following visual scale of erythema (from 0 to 4).The assessment was conducted at 30 min and at 48 h post-PDT. RESULTS In the assessment at 48 h after treatment, the inflammation had improved more among the patients treated with OC (median: 25%, 95%CI: -5.3 to 28.5) than in the non-OC group (median: 0%; 95%CI: -45.2 to -6.2). The difference was statistically significant (p<0.01), and the Cohen's d value was 0.89 (large effect). At three months after PDT, a complete response had been obtained by 60.9% of the patients treated with OC compared to 29.2% of the non-OC group, and the difference was close to statistical significance (p=0.059). CONCLUSIONS The topical application of an oily fluid enriched with OC extract achieved a greater reduction in post-PDT cutaneous inflammation and a better treatment response, in comparison with the application of a conventional oily fluid.
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Combination of tacalcitol ointment and photodynamic therapy for the treatment of follicular mucinosis of the scalp.
Giuffrida, R, Borgia, F, Marafioti, I, Riso, G, Cannavò, SP
Photodiagnosis and photodynamic therapy. 2019;:487-489
Abstract
Follicular mucinosis (FM) is a rare inflammatory disorder histologically characterized by mucin deposition in the follicular epithelium. There is no standard therapy for FM and several treatments have been described in the literature. We present the case of a 59 year-old female affected by a recalcitrant FM with diffuse scalp alopecia, in which complete clinical remission was achieved after a combination of topical tacalcitol and photodynamic therapy.