Assessing the Effect of Surface Coating on the Stability, Degradation, Toxicity and Cell Endocytosis/Exocytosis of Upconverting Nanoparticles.

Lanthanide-doped up-converting nanoparticles (UCNPs) have emerged as promising biomedical tools in recent years. Most research efforts were devoted to the synthesis of inorganic cores with the optimal physicochemical properties. However, the careful design of UCNPs with the adequate surface coating to optimize their biological performance still remains a significant challenge. Here, we propose the functionalization of UCNPs with four distinct types of surface coatings, which were compared in terms of the provided colloidal stability and resistance to degradation in different biological-relevant media, including commonly avoided analysis in acidic lysosomal-mimicking fluids. Moreover, the influence of the type of particle surface coating on cell cytotoxicity and endocytosis/exocytosis was also evaluated. The obtained results demonstrated that the functionalization of UCNPs with poly(isobutylene-alt-maleic anhydride) grafted with dodecylamine (PMA-g-dodecyl) constitutes an outstanding strategy for their subsequent biomedical application, whereas poly(ethylene glycol) (PEG) coating, although suitable for colloidal stability purposes, hinders extensive cell internalization. Conversely, surface coating with small ligand were found not to be suitable, leading to large degradation degrees of UCNPs. The analysis of particle' behavior in different biological media and in vitro conditions here performed pretends to help researchers to improve the design and implementation of UCNPs as theranostic nanotools.

Hierarchical Design of Tissue-Mimetic Fibrillar Hydrogel Scaffolds.

Most tissues of the human body present hierarchical fibrillar extracellular matrices (ECMs) that have a strong influence over their physicochemical properties and biological behavior. Of great interest is the introduction of this fibrillar structure to hydrogels, particularly due to the water-rich composition, cytocompatibility, and tunable properties of this class of biomaterials. Here, the main bottom-up fabrication strategies for the design and production of hierarchical biomimetic fibrillar hydrogels and their most representative applications in the fields of tissue engineering and regenerative medicine are reviewed. For example, the controlled assembly/arrangement of peptides, polymeric micelles, cellulose nanoparticles (NPs), and magnetically responsive nanostructures, among others, into fibrillar hydrogels is discussed, as well as their potential use as fibrillar-like hydrogels (e.g., those from cellulose NPs) with key biofunctionalities such as electrical conductivity or remote stimulation. Finally, the major remaining barriers to the clinical translation of fibrillar hydrogels and potential future directions of research in this field are discussed.

Metabolomic profile of neuroendocrine tumors identifies methionine, porphyrin, and tryptophan metabolisms as key dysregulated pathways associated with patient survival.

OBJECTIVE: Metabolic profiling is a valuable tool to characterize tumor biology but remains largely unexplored in neuroendocrine tumors (NETs). Our aim was to comprehensively assess the metabolomic profile of NETs and identify novel prognostic biomarkers and dysregulated molecular pathways. DESIGN AND METHODS: Multiplatform untargeted metabolomic profiling (GC-MS, CE-MS, and LC-MS) was performed in plasma from 77 patients with G1-2 extra-pancreatic NETs enrolled in the AXINET trial (NCT01744249) (study cohort) and from 68 non-cancer individuals (control). The prognostic value of each differential metabolite (n = 155) in NET patients (P < .05) was analyzed by univariate and multivariate analyses adjusted for multiple testing and other confounding factors. Related pathways were explored by Metabolite Set Enrichment Analysis (MSEA) and Metabolite Pathway Analysis (MPA). RESULTS: Thirty-four metabolites were significantly associated with progression-free survival (PFS) (n = 16) and/or overall survival (OS) (n = 27). Thirteen metabolites remained significant independent prognostic factors in multivariate analysis, 3 of them with a significant impact on both PFS and OS. Unsupervised clustering of these 3 metabolites stratified patients in 3 distinct prognostic groups (1-year PFS of 71.1%, 47.7%, and 15.4% (P = .012); 5-year OS of 69.7%, 32.5%, and 27.7% (P = .003), respectively). The MSEA and MPA of the 13-metablolite signature identified methionine, porphyrin, and tryptophan metabolisms as the 3 most relevant dysregulated pathways associated with the prognosis of NETs. CONCLUSIONS: We identified a metabolomic signature that improves prognostic stratification of NET patients beyond classical prognostic factors for clinical decisions. The enriched metabolic pathways identified reveal novel tumor vulnerabilities that may foster the development of new therapeutic strategies for these patients.

Inhibiting HER3 Hyperphosphorylation in HER2-Overexpressing Breast Cancer through Multimodal Therapy with Branched Gold Nanoshells.

Treatment failure in breast cancers overexpressing human epidermal growth factor receptor 2 (HER2) is associated mainly to the upregulation of human epidermal growth factor receptor 3 (HER3) oncoprotein linked to chemoresitence. Therefore, to increase patient survival, here a multimodal theranostic nanoplatform targeting both HER2 and HER3 is developed. This consists of doxorubicin-loaded branched gold nanoshells functionalized with the near-infrared (NIR) fluorescent dye indocyanine green, a small interfering RNA (siRNA) against HER3, and the HER2-specific antibody Transtuzumab, able to provide a combined therapeutic outcome (chemo- and photothermal activities, RNA silencing, and immune response). In vitro assays in HER2+ /HER3+ SKBR-3 breast cancer cells have shown an effective silencing of HER3 by the released siRNA and an inhibition of HER2 oncoproteins provided by Trastuzumab, along with a decrease of the serine/threonine protein kinase Akt (p-AKT) typically associated with cell survival and proliferation, which helps to overcome doxorubicin chemoresistance. Conversely, adding the NIR light therapy, an increment in p-AKT concentration is observed, although HER2/HER3 inhibitions are maintained for 72 h. Finally, in vivo studies in a tumor-bearing mice model display a significant progressively decrease of the tumor volume after nanoparticle administration and subsequent NIR light irradiation, confirming the potential efficacy of the hybrid nanocarrier.

Advances in the Treatment of Gastroenteropancreatic Neuroendocrine Carcinomas: Are we Moving Forward?

Poorly differentiated gastroenteropancreatic neuroendocrine carcinomas are aggressive neoplasms of challenging clinical management. A small proportion of patients with early-stage disease may achieve long-term survival, but the majority of patients present with rapidly lethal metastatic disease. Current standard of care still follows the treatment paradigm of small cell lung cancer, a far more common G3 neuroendocrine neoplasm, although emerging molecular and clinical data increasingly question this approach. In this article, we will briefly summarize epidemiology and prognosis of gastroenteropancreatic neuroendocrine carcinomas to emphasize the very low incidence, aggressive nature, and orphan status of this tumor entity. We will also discuss the current pathological classification and its limitations, as well as recent data on their differential biological background compared with small cell lung cancer, and its potential implications for patients care. Then, we will review the standard of care of systemic therapy, basically focused on platinum-based cytotoxic chemotherapy, including some recent randomized trials providing evidence regarding efficacy of irinotecan vs etoposide platinum doublets. Finally, we will present a comprehensive overview of novel therapeutic strategies in current clinical development, including recently reported data on immunotherapy, tumor-agnostic therapies (microsatellite instability, high tumor mutational burden, NTRK and RET gene fusions, BRAF or KRAS inhibitors), and additional treatment strategies targeting other tumor vulnerabilities (ie, Notch pathway, novel targets for radioligand therapy), and provide some insights regarding unmet needs and future perspectives to improve patient's care and prognosis.

MicroRNA signature and integrative omics analyses define prognostic clusters and key pathways driving prognosis in patients with neuroendocrine neoplasms.

Neuroendocrine neoplasms (NENs) are mutationally quiet (low number of mutations/Mb), and epigenetic mechanisms drive their development and progression. We aimed at comprehensively characterising the microRNA (miRNA) profile of NENs, and exploring downstream targets and their epigenetic modulation. In total, 84 cancer-related miRNAs were analysed in 85 NEN samples from lung and gastroenteropancreatic (GEP) origin, and their prognostic value was evaluated by univariate and multivariate models. Transcriptomics (N = 63) and methylomics (N = 30) were performed to predict miRNA target genes, signalling pathways and regulatory CpG sites. Findings were validated in The Cancer Genome Atlas cohorts and in NEN cell lines. We identified a signature of eight miRNAs that stratified patients in three prognostic groups (5-year survival of 80%, 66% and 36%). Expression of the eight-miRNA gene signature correlated with 71 target genes involved in PI3K-Akt and TNFα-NF-kB signalling. Of these, 28 were associated with survival and validated in silico and in vitro. Finally, we identified five CpG sites involved in the epigenetic regulation of these eight miRNAs. In brief, we identified an 8-miRNA signature able to predict survival of patients with GEP and lung NENs, and identified genes and regulatory mechanisms driving prognosis in NEN patients.

Tenofovir Disoproxil Fumarate Reduces the Severity of COVID-19 in Patients with Chronic Hepatitis B.

BACKGROUND AND AIMS: HIV-positive patients on tenofovir hydroxyl fumarate (TDF)/emtricitabine have a lower risk of COVID-19 and hospitalization than those given other treatments. Our aim was to analyze the severity of COVID-19 in patients with chronic hepatitis B (CHB) on TDF or entecavir (ETV). METHODS: Spanish hospital databases (n = 28) including information regarding adult CHB patients on TDF or ETV for the period February 1st to November 30th 2020 were searched for COVID-19, defined as a positive SARS-CoV-2 polymerase chain reaction, and for severe COVID-19. RESULTS: Of 4736 patients, 117 had COVID-19 (2.5%), 67 on TDF and 50 on ETV. Compared to patients on TDF, those on ETV showed (p < 0.05) greater rates of obesity, diabetes, ischemic cardiopathy, and hypertension. COVID-19 incidence was similar in both groups (2.3 vs. 2.6%). Compared to TDF, patients on ETV more often (p < 0.01) had severe COVID-19 (36 vs. 6%), required intensive care unit (ICU) (10% vs. 0) or ventilatory support (20 vs. 3%), were hospitalized for longer (10.8 ± 19 vs. 3.1 ± 7 days) or died (10 vs. 1.5%, p = 0.08). In an IPTW propensity score analysis adjusted for age, sex, obesity, comorbidities, and fibrosis stage, TDF was associated with a sixfold reduction in severe COVID-19 risk (adjusted-IPTW-OR 0.17, 95%CI 0.04-0.67, p = 0.01). CONCLUSION: Compared to ETV, TDF seems to play a protective role in CHB patients with SARS-CoV-2 whereby the risk of severe COVID-19 is lowered.

Development of functional hybrid scaffolds for wound healing applications.

Hybrid hydrogels composed of chitosan (CS) and hyaluronic acid (HA) and collagen (Coll) were prepared by polyelectrolyte complex self-assembly. These scaffolds displayed a good intermingling of the polymeric chains, with porosities above 80% and good interconnected structures with pore sizes lying between 30-115 µm. The ionic interactions between CS and HA make the scaffolds have larger storage modulus and longer LVR regions than their pure counterparts. Both quantities progressively decrease as the HA and Coll concentrations in the formulation rise. These hybrid hydrogels showed good swelling extents from ca. 420 to ca. 690% and suitable resistance to enzymatic degradation, which was slightly lower for scaffolds containing CS to larger extents or Coll in the formulation. All scaffolds were largely cytocompatible and allowed the proliferation of both mouse fibroblast and human keratinocytes with their infiltration inside, thus becoming optimal matrices for intended tissue engineering applications as well as transdermal drug delivery depots.

Combined Therapeutics for Atherosclerosis Treatment Using Polymeric Nanovectors.

Atherosclerosis is an underlying risk factor in cardiovascular diseases (CVDs). The combination of drugs with microRNAs (miRNA) inside a single nanocarrier has emerged as a promising anti-atherosclerosis strategy to achieve the exploitation of their complementary mechanisms of action to achieve synergistic therapeutic effects while avoiding some of the drawbacks associated with current systemic statin therapies. We report the development of nanometer-sized polymeric PLGA nanoparticles (NPs) capable of simultaneously encapsulating and delivering miRNA-124a and the statin atorvastatin (ATOR). The polymeric NPs were functionalized with an antibody able to bind to the vascular adhesion molecule-1 (VCAM1) overexpressed in the inflamed arterial endothelium. The dual-loaded NPs were non-toxic to cells in a large range of concentrations, successfully attached overexpressed VCAM receptors and released the cargoes in a sustainable manner inside cells. The combination of both ATOR and miRNA drastically reduced the levels of proinflammatory cytokines such as IL-6 and TNF-α and of reactive oxygen species (ROS) in LPS-activated macrophages and vessel endothelial cells. In addition, dual-loaded NPs precluded the accumulation of low-density lipoproteins (LdL) inside macrophages as well as morphology changes to a greater extent than in single-loaded NPs. The reported findings validate the present NPs as suitable delivery vectors capable of simultaneously targeting inflamed cells in atherosclerosis and providing an efficient approach to combination nanomedicines.

Comprehensive Plasma Metabolomic Profile of Patients with Advanced Neuroendocrine Tumors (NETs). Diagnostic and Biological Relevance.

PURPOSE: High-throughput "-omic" technologies have enabled the detailed analysis of metabolic networks in several cancers, but NETs have not been explored to date. We aim to assess the metabolomic profile of NET patients to understand metabolic deregulation in these tumors and identify novel biomarkers with clinical potential. METHODS: Plasma samples from 77 NETs and 68 controls were profiled by GC-MS, CE-MS and LC-MS untargeted metabolomics. OPLS-DA was performed to evaluate metabolomic differences. Related pathways were explored using Metaboanalyst 4.0. Finally, ROC and OPLS-DA analyses were performed to select metabolites with biomarker potential. RESULTS: We identified 155 differential compounds between NETs and controls. We have detected an increase of bile acids, sugars, oxidized lipids and oxidized products from arachidonic acid and a decrease of carnitine levels in NETs. MPA/MSEA identified 32 enriched metabolic pathways in NETs related with the TCA cycle and amino acid metabolism. Finally, OPLS-DA and ROC analysis revealed 48 metabolites with diagnostic potential. CONCLUSIONS: This study provides, for the first time, a comprehensive metabolic profile of NET patients and identifies a distinctive metabolic signature in plasma of potential clinical use. A reduced set of metabolites of high diagnostic accuracy has been identified. Additionally, new enriched metabolic pathways annotated may open innovative avenues of clinical research.

Engineering next-generation bioinks with nanoparticles: moving from reinforcement fillers to multifunctional nanoelements.

The application of additive manufacturing in the biomedical field has become a hot topic in the last decade owing to its potential to provide personalized solutions for patients. Different bioinks have been designed trying to obtain a unique concoction that addresses all the needs for tissue engineering and drug delivery purposes, among others. Despite the remarkable progress made, the development of suitable bioinks which combine printability, cytocompatibility, and biofunctionality is still a challenge. In this sense, the well-established synthetic and functionalization routes to prepare nanoparticles with different functionalities make them excellent candidates to be combined with polymeric systems in order to generate suitable multi-functional bioinks. In this review, we briefly discuss the most recent advances in the design of functional nanocomposite hydrogels considering their already evaluated or potential use as bioinks. The scientific development over the last few years is reviewed, focusing the discussion on the wide range of functionalities that can be incorporated into 3D bioprinted constructs through the addition of multifunctional nanoparticles in order to increase their regenerative potential in the field of tissue engineering.

Magnetic Nanocomposite Hydrogels for Tissue Engineering: Design Concepts and Remote Actuation Strategies to Control Cell Fate.

Most tissues of the human body are characterized by highly anisotropic physical properties and biological organization. Hydrogels have been proposed as scaffolding materials to construct artificial tissues due to their water-rich composition, biocompatibility, and tunable properties. However, unmodified hydrogels are typically composed of randomly oriented polymer networks, resulting in homogeneous structures with isotropic properties different from those observed in biological systems. Magnetic materials have been proposed as potential agents to provide hydrogels with the anisotropy required for their use on tissue engineering. Moreover, the intrinsic properties of magnetic nanoparticles enable their use as magnetomechanic remote actuators to control the behavior of the cells encapsulated within the hydrogels under the application of external magnetic fields. In this review, we combine a detailed summary of the main strategies to prepare magnetic nanoparticles showing controlled properties with an analysis of the different approaches available to their incorporation into hydrogels. The application of magnetically responsive nanocomposite hydrogels in the engineering of different tissues is also reviewed.

Natural-Based Hydrogels for Tissue Engineering Applications.

In the field of tissue engineering and regenerative medicine, hydrogels are used as biomaterials to support cell attachment and promote tissue regeneration due to their unique biomimetic characteristics. The use of natural-origin materials significantly influenced the origin and progress of the field due to their ability to mimic the native tissues' extracellular matrix and biocompatibility. However, the majority of these natural materials failed to provide satisfactory cues to guide cell differentiation toward the formation of new tissues. In addition, the integration of technological advances, such as 3D printing, microfluidics and nanotechnology, in tissue engineering has obsoleted the first generation of natural-origin hydrogels. During the last decade, a new generation of hydrogels has emerged to meet the specific tissue necessities, to be used with state-of-the-art techniques and to capitalize the intrinsic characteristics of natural-based materials. In this review, we briefly examine important hydrogel crosslinking mechanisms. Then, the latest developments in engineering natural-based hydrogels are investigated and major applications in the field of tissue engineering and regenerative medicine are highlighted. Finally, the current limitations, future challenges and opportunities in this field are discussed to encourage realistic developments for the clinical translation of tissue engineering strategies.

Oxidized lipids in the metabolic profiling of neuroendocrine tumors - Analytical challenges and biological implications.

Untargeted metabolomics can be a great tool for exploring new scientific areas; however, wrong metabolite annotation questions the credibility and puts the success of the entire research at risk. Therefore, an effort should be made to improve the quality and robustness of the annotation despite of the challenges, especially when final identification with standards is not possible. Through non-targeted analysis of human plasma samples, from a large cancer cohort study using RP-LC-ESI-QTOF-MS/MS, we have resolved MS/MS annotation through spectral matching, directed to hydroxyeicosatetraenoic acids (HETEs) and, MS/MS structural elucidation for newly annotated oxidized lyso-phosphatidylcholines (oxLPCs). The annotation of unknowns is supported with structural information from fragmentation spectra as well as the fragmentation mechanisms involved, necessarily including data from both polarity modes and different collision energies. In this work, we present evidences that various oxidation products show significant differences between cancer patients and control individuals and we establish a workflow to help identify such modifications. We report here the upregulation of HETEs and oxLPCs in patients with neuroendocrine tumors (NETs). To our knowledge, this is the first attempt to determine HETEs in NETs and one of very few studies where oxLPCs are annotated. The obtained results provide an important insight regarding lipid oxidation in NETs, although their physiological functions still have to be established and require further research.

Cubic Anisotropic Co- and Zn-Substituted Ferrite Nanoparticles as Multimodal Magnetic Agents.

The use of magnetic nanoparticles as theranostic agents for the detection and treatment of cancer diseases has been extensively analyzed in the last few years. In this work, cubic-shaped cobalt and zinc-doped iron oxide nanoparticles with edge lengths in the range from 28 to 94 nm are proposed as negative contrast agents for magnetic resonance imaging and to generate localized heat by magnetic hyperthermia, obtaining high values of transverse relaxation coefficients and specific adsorption rates. The applied magnetic fields presented suitable characteristics for the potential validation of the results into the clinical practice in all cases. Pure iron oxide and cobalt- and zinc-substituted ferrites have been structurally and magnetically characterized, observing magnetite as the predominant phase and weak ferrimagnetic behavior at room temperature, with saturation values even larger than those of bulk magnetite. The coercive force increased due to the incorporation of cobalt ions, while zinc substitution promotes a significant increase in saturation magnetization. After their transfer to aqueous solution, those particles showing the best properties were chosen for evaluation in in vitro cell models, exhibiting high critical cytotoxic concentrations and high internalization degrees in several cell lines. The magnetic behavior of the nanocubes after their successful cell internalization was analyzed, detecting negligible variations on their magnetic hysteresis loops and a significant decrease in the specific adsorption rate values.

Effects of A Dual-Task Intervention in Postural Control and Cognitive Performance in Adolescents.

The aim was to assess dual- versus single-task training for motor performance and cognitive performance in adolescents. Two experiments were performed. In the first, 30 adolescents were randomized to three groups to determine the effect of dual-task difficulty on postural control: α-scaling and root mean square (RMS). In the second, 20 adolescents were randomized to two groups to determine the effect of dual-task practice to improve working memory. RMS in the post-test was lower than the pre-test in both dual-task groups, while α-scaling was lower in post-test than pre-test only in the high-difficulty dual-task group. A practice effect was observed on the percentage of correct answers only in the dual-task group (p = 0.035). Thus, dual-task training could enhance motor and cognitive performance more than single-task training.

Integrated miRNA and mRNA expression profiling identifies novel targets and pathological mechanisms in autoimmune thyroid diseases.

BACKGROUND: The mechanisms underlying autoimmune thyroid disease (AITD) remain elusive. Identification of such mechanisms would reveal novel and/or better therapeutic targets. Here, we use integrated analysis of miRNAs and mRNAs expression profiling to identify potential therapeutic targets involved in the mechanisms underlying AITD. METHODS: miRNA and mRNA from twenty fresh-frozen thyroid tissues (15 from AITD patients and 5 from healthy controls) were subjected to next-generation sequencing. An anti-correlated method revealed potential pathways and disease targets, including proteins involved in the formation of primary cilia. Thus, we examined the distribution and length of primary cilia in thyroid tissues from AITD and controls using immunofluorescence and scanning electron microscopy, and parsed cilia formation in thyroid cell lines in response to inflammatory stimuli in the presence of miRNA mimics. FINDINGS: We found that the expression of miR-21-5p, miR-146b-3p, miR-5571-3p and miR-6503-3p was anti-correlated with Enolase 4 (ENO4), in-turned planar cell polarity protein (INTU), kinesin family member 27 (KIF27), parkin co-regulated (PACRG) and serine/threonine kinase 36 (STK36) genes. Functional classification of these miRNA/mRNAs revealed that their differential expression was associated with cilia organization. We demonstrated that the number and length of primary cilia in thyroid tissues was significantly lower in AITD than in control (frequency of follicular ciliated cells in controls = 67.54% vs a mean of 22.74% and 21.61% in HT and GD respectively p = 0.0001, by one-way ANOVA test). In addition, pro-inflammatory cytokines (IFNγ and TNFα) and specific miRNA mimics for the newly identified target genes affected cilia appearance in thyroid cell lines. INTERPRETATION: Integrated miRNA/gene expression analysis has identified abnormal ciliogenesis as a novel susceptibility pathway that is involved in the pathogenesis of AITD. These results reflect that ciliogenesis plays a relevant role in AITD, and opens research pathways to design therapeutic targets in AITD. FUNDING: Instituto de Salud Carlos III, Comunidad de Madrid, Grupo Español de Tumores Neuroendocrinos y Endocrinos, Ministerio de Economía y Empresa and FEDER.

Triggered RNAi Therapy Using Metal Inorganic Nanovectors.

The administration of small interfering RNA (siRNA) is a very interesting therapeutic option to treat genetic diseases such as Alzheimer's or some types of cancer, but its effective delivery still remains a challenge. Herein, Au nanorod (GNR)-based platforms functionalized with polyelectrolyte layers were developed and analyzed as potential siRNA nanocarriers. The polymeric layers were successfully assembled on the particle surfaces by means of the layer-by-layer assembly technique through the alternating deposition of oppositely charged poly(styrene)sulfonate, PSS, poly(lysine), PLL, and siRNA biopolymers, with a final hyaluronic acid layer in order to provide the nanoconstructs with a potential targeting ability as well as colloidal stability in physiological medium. Once the hybrid nanocarriers were obtained, the cargo release, their colloidal stability in physiological-relevant media, cytotoxicity, cellular internalization and uptake, and knockdown activity were studied. The present hybrid particles release the genetic material inside cells by means of a protease-assisted and/or a light-triggered release mechanism in order to control the delivery of the oligonucleotides on demand. In addition, the hybrid nanovectors were observed to be nontoxic to cells and could efficiently deliver the genetic material in the cell cytoplasms. The GNR-based nanocarriers proposed here can provide a suitable environment to load and protect a sufficient amount of the genetic material to allow an efficient and sustained knockdown gene expression for long (up to 93% for 72 h), thanks to the slow degradation of PLL, without the observation of adverse side toxic effects. It was also found that the silencing activity was enhanced with the number of siRNA layers assembled in the nanoplatforms.

A study of reproducibility of kinesiology tape applications: review, reliability and validity.

BACKGROUND: Literature addressing the mechanical properties of kinesiology tape is quite scarce. There are no studies which focus on the mechanical characteristics of kinesiology tape, its mechanical properties, nor its adherence following the ISO international standard test methods for tape elongation. METHODS: This study quantified the mechanical characteristics of 380 samples of kinesiology tape from 19 different brands and in 4 different colors using a dynamometer. Mechanical testing was controlled by UNE EN ISO 13934-1. RESULTS: Significant differences were found between tape brands in terms of grammage, maximum force tenacity, work, pre-elongation and percentage elongation (P < .001). Regarding kinesiology tape color, statistically significant differences were found between tape brands in terms of grammage, maximum force and tenacity (P < .001), work and pre-elongation (P < .05). When adherence was studied, statistically significant differences were found between tape brands in terms of maximum force and work (P < .001). CONCLUSIONS: The different kinesiology tapes presented different behaviors with regard to rupture and removal when applied to skin in dry state, wet state and after being submerged in artificial acidic sweat solution. Therefore, different kinesiology tape brands will produce different levels of strain even though the same elongation is used. Depending on the characteristics (body dimensions) and properties (skin elongation) of each subject in the sample, bandages with different elongations must be applied to achieve the same strain in all of the tapes and therefore produce the same effect. The absence of these data at this time limits the reliability of previous clinical studies, makes comparing their findings impossible and presents new challenges for research in this field.

Gold Nanorod-Based Nanohybrids for Combinatorial Therapeutics.

In this work, multifunctional nanocarriers consisting of poly(sodium-4-styrenesulfonate) (PSS)/doxorubicin (DOXO)/poly-l-lysine hydrobromide (PLL)/hyaluronic acid (HA)-coated and (PSS/DOXO/PLL)2/HA-coated gold nanorods were assembled by the layer-by-layer technique with the aims of coupling the plasmonic photothermal properties of the metal nanoparticles for plasmonic hyperthermia and the chemoaction of drug DOXO for potential intended combinatorial cancer therapeutics in the future as well as providing different strategies for the controlled and sustained release of the cargo drug molecules. To do that, DOXO could be successfully loaded onto the hybrid nanoconstructs through electrostatic interactions with high efficiencies of up to ca. 78.3 ± 6.9% for the first formed drug layer and 56 ± 13% for the second one, with a total efficiency for the whole system [(PSS/DOXO/PLL)2/HA-coated NRs] of ca. 65.7 ± 1.4%. Nanohybrid internalization was observed to be enhanced by the outer HA layer, which is able to target the CD44 receptors widely overexpressed in some types of cancers as lung, breast, or ovarian ones. Hence, these nanohybrid systems might be versatile nanoplatforms to simultaneously deliver sufficient heat for therapeutic plasmonic hyperthermia and the anticancer drug. Two controlled mechanisms were proposed to modulate the release of the chemodrug, one by means of the enzymatic degradable character of the PLL layer and another by the modulation of the interactions between the polymeric layers through the exploitation of the optical properties of the hybrid particles under near infrared (NIR) laser irradiation. The combination of this bimodal therapeutic approach exerted a synergistic cytotoxic effect on both HeLa and MDA-MB-231 cancer cells in vitro. Cell death mechanisms were also analyzed, elucidating that plasmonic photothermal therapy induces cell necrosis, whereas DOXO activates the cell apoptotic pathway. Therefore, the present NIR laser-induced targeted cancer thermo/chemotherapy represents a novel targeted anticancer strategy with easy control on demand and suitable therapeutic efficacy.