Correction: Understanding the Role of Growth Factors in Modulating Stem Cell Tenogenesis.

[This corrects the article DOI: 10.1371/journal.pone.0083734.].

Açaí Flan, A Functional Food with Lacticaseibacillus rhamnosus HN001 Probiotic: Physicochemical Characteristics, Probiotic Survival, Sensory Acceptance and Consumer Perception.

Research background: Açaí berry is rich in antioxidant compounds and is therefore closely associated with beneficial health effects. In this study, we aim to investigate the potential of using Lacticaseibacillus rhamnosus HN001 as a probiotic culture on açaí flan. Experimental approach: The chemical composition, physicochemical and microbiological characteristics, and sensory acceptance during refrigerated storage (5 °C for 42 days) of flan were investigated. In addition, the consumer perception of the product was evaluated using word association when consumers were shown a photo of the product with or without the added ingredients accompanied with a brief description of the product. Results and conclusions: The flan had a suitable chemical composition, mainly carbohydrates and proteins, probiotic viability reached 8 log CFU/g in the product and 4 log CFU/g after gastrointestinal simulation, typical açaí coloration, significant antioxidant activity and high sensory acceptability. The information about the ingredients and properties of the products increased the health value and positive feelings of the consumers towards the product. Novelty and scientific contribution: Açaí flan has proven to be a suitable carrier for L. rhamnosus HN001 as a probiotic culture, further enhancing the characteristic beneficial properties of the fruit. Therefore, combining this information with marketing strategies that inform consumers about the benefits of the product can further improve its acceptance. As far as we know, this is the first study on açaí flan with added probiotic culture.

A Rare Cause of Intellectual Disability.

A seven-year-old female was followed in a developmental clinic from the age of nine months due to delayed psychomotor development. The first physical examination showed a newborn with irritability and a large anterior fontanelle. A transfontanellar ultrasound was performed, revealing mild enlargement of the lateral and third ventricles. Head circumference remained below the third percentile until the age of five months, then rose to the third percentile. Developmental milestones were globally delayed, with expressive language being more severely affected and axial hypotonia with appendicular hypertonia on neurological examination. Subsequent medical observation revealed deep-set eyes, mildly up-slanted palpebral fissures, a high nasal bridge with a broad nasal tip, a thin upper lip, widely spaced teeth, retrognathia, and a slight pectus excavatum. Genetic investigation revealed the diagnosis, with whole-exome sequencing consistent with the genetic diagnosis of autosomal dominant mental retardation type 7 (MRD7). All patients diagnosed with MRD7 have a development delay detected at a young age and, typically, a mild to severe intellectual disability later in life. All individuals present language impairment, especially in verbal expression. Motor development is typically affected by gait disturbances and generalized hypertonia, which are noted early in life. Microcephaly is a prominent feature of this syndrome, present in over 90% of the cases. The most common findings in MRD7 (microcephaly and intellectual disability) have a broad differential diagnosis. Some disorders have multiple findings in common with MRD7, such as Angelman syndrome (AS), MECP2 disorders, or Mowat-Wilson syndrome (MWS). MRD7 is a rare genetic syndrome characterized by developmental delay/intellectual disability, microcephaly, autism spectrum disorder, behavior problems, typical facial features, and seizures. Early intervention is more likely to be effective and potentially change a child's developmental path. Small gains early in life could represent a significant difference in the children's future autonomy.

Biocompatible 3D-Printed Tendon/Ligament Scaffolds Based on Polylactic Acid/Graphite Nanoplatelet Composites.

Three-dimensional (3D) printing technology has become a popular tool to produce complex structures. It has great potential in the regenerative medicine field to produce customizable and reproducible scaffolds with high control of dimensions and porosity. This study was focused on the investigation of new biocompatible and biodegradable 3D-printed scaffolds with suitable mechanical properties to assist tendon and ligament regeneration. Polylactic acid (PLA) scaffolds were reinforced with 0.5 wt.% of functionalized graphite nanoplatelets decorated with silver nanoparticles ((f-EG)+Ag). The functionalization of graphene was carried out to strengthen the interface with the polymer. (f-EG)+Ag exhibited antibacterial properties against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), an important feature for the healing process and prevention of bacterial infections. The scaffolds' structure, biodegradation, and mechanical properties were assessed to confirm their suitability for tendon and ligamentregeneration. All scaffolds exhibited surface nanoroughness created during printing, which was increased by the filler presence. The wet state dynamic mechanical analysis proved that the incorporation of reinforcement led to an increase in the storage modulus, compared with neat PLA. The cytotoxicity assays using L929 fibroblasts showed that the scaffolds were biocompatible. The PLA+[(f-EG)+Ag] scaffolds were also loaded with human tendon-derived cells and showed their capability to maintain the tenogenic commitment with an increase in the gene expression of specific tendon/ligament-related markers. The results demonstrate the potential application of these new 3D-printed nanocomposite scaffolds for tendon and ligament regeneration.

Contactless Resolution of Inflammatory Signals in Tailored Macrophage-Based Cell Therapeutics.

In recent years, nanotechnology-based microRNA (miR) therapeutic platforms have shown great promise for immunotherapy and tissue regeneration, despite the unmet challenge of achieving efficient and safe delivery of miRs. The transport of miRs offers precision and regulatory value for a myriad of biological processes and pathways, including the control of macrophage (Mφ) functions and, consequently, the inflammatory cascades Mφ are involved in. Thus, enforcement of Mφ can boost the regenerative process and provide new solutions for diverse chronic pathologies. In this study, we sought to develop a magnetically guided transporter to deliver an miR-155 antagonist to M1-primed Mφ. Furthermore, we determined its modulatory effect in reprogramming Mφ from inflammatory to pro-regenerative phenotypes, with the aim of tissue healing and regenerative medicine approaches. This strategy combines contactless and high-precision control of Mφ, anticipating new functional miR carriers for targeted strategies controlled by extracorporeal action. The magnetoplexes SPION@PEI-miR were efficiently delivered into Mφ without compromising cell viability and successfully induced miR-mediated gene silencing by enhancing the expression of anti-inflammatory markers (IL4 and IL10) and the production of M2φ-related markers (CD206 and IL4). Given its multimodal features, SPION@PEI-miR represents a simple, safe, and nonviral theranostic platform that enables imaging, tracking, and miR delivery with modulatory effects on immune cells.

Brazilian consensus for diagnosis, management and treatment of hereditary transthyretin amyloidosis with peripheral neuropathy: second edition.

Hereditary transthyretin amyloidosis with peripheral neuropathy (ATTRv-PN) is an autosomal dominant inherited sensorimotor and autonomic polyneuropathy with over 130 pathogenic variants identified in the TTR gene. Hereditary transthyretin amyloidosis with peripheral neuropathy is a disabling, progressive and life-threatening genetic condition that leads to death in ∼ 10 years if untreated. The prospects for ATTRv-PN have changed in the last decades, as it has become a treatable neuropathy. In addition to liver transplantation, initiated in 1990, there are now at least 3 drugs approved in many countries, including Brazil, and many more are being developed. The first Brazilian consensus on ATTRv-PN was held in the city of Fortaleza, Brazil, in June 2017. Given the new advances in the area over the last 5 years, the Peripheral Neuropathy Scientific Department of the Brazilian Academy of Neurology organized a second edition of the consensus. Each panelist was responsible for reviewing the literature and updating a section of the previous paper. Thereafter, the 18 panelists got together virtually after careful review of the draft, discussed each section of the text, and reached a consensus for the final version of the manuscript.

Polineuropatia amiloidótica familiar associada a transtirretina (ATTRv-PN) é uma polineuropatia sensitivo-motora e autonômica hereditária autossômica dominante com mais de 130 variantes patogênicas já identificadas no gene TTR. A ATTRv-PN é uma condição genética debilitante, progressiva e que ameaça a vida, levando à morte em ∼ 10 anos se não for tratada. Nas últimas décadas, a ATTRv-PN se tornou uma neuropatia tratável. Além do transplante de fígado, iniciado em 1990, temos agora 3 medicamentos modificadores de doença aprovados em muitos países, incluindo o Brasil, e muitas outras medicações estão em desenvolvimento. O primeiro consenso brasileiro em ATTRv-PN foi realizado em Fortaleza em junho de 2017. Devido aos novos avanços nesta área nos últimos 5 anos, o Departamento Científico de Neuropatias Periféricas da Academia Brasileira de Neurologia organizou uma segunda edição do consenso. Cada panelista ficou responsável por rever a literatura e atualizar uma parte do manuscrito. Finalmente, os 18 panelistas se reuniram virtualmente após revisão da primeira versão, discutiram cada parte do artigo e chegaram a um consenso sobre a versão final do manuscrito.

Prospects of magnetically based approaches addressing inflammation in tendon tissues.

Tendon afflictions constitute a significant share of musculoskeletal diseases and represent a primary cause of incapacity worldwide. Unresolved/chronic inflammatory states have been associated with the onset and progression of tendon disorders, contributing to undesirable immune stimulation and detrimental tissue effects. Thus, targeting persistent inflammatory events could assist important developments to solve pathophysiological processes and innovative therapeutics to address impaired healing and accomplish complete tendon regeneration. This review overviews the impact of inflammation and inflammatory mediators in tendon niches, unveiling the importance of tendon cell populations and their signature features, and the influence of microenvironmental factors on inflamed and injured tendons. The demand for non-invasive instructive strategies to manage persistent inflammatory mediators, guide inflammatory pathways, and modulate cellular responses will also be approached by exploring the role of pulsed electromagnetic field (PEMF). PEMF alone or combined with more sophisticated systems triggered by magnetic fields will be considered in the design of successful therapies to control inflammation in tendinopathic conditions.

Hemolytic-uremic syndrome: 24 years' experience of a pediatric nephrology unit / Síndrome hemolítico-urêmica: 24 anos de experiência de uma unidade de nefrologia pediátrica

Abstract Introduction: A better understanding of hemolytic-uremic syndrome (HUS) pathophysiology significantly changed its treatment and prognosis. The aim of this study is to characterize the clinical features, severity, management, and outcomes of HUS patients. Materials and Methods: Retrospective study of HUS patients admitted to a Pediatric Nephrology Unit between 1996 and 2020. Demographic and clinical data regarding etiology, severity, treatment strategies, and patient outcome were collected. Results: Twenty-nine patients with HUS were admitted to our unit, but four were excluded. Median age at diagnosis was two years (2 months - 17 years). Clinical manifestations included diarrhea, vomiting, oliguria, hypertension, and fever. During the acute phase, 14 patients (56%) required renal replacement therapy. Infectious etiology was identified in seven patients (five Escherichia coli and two Streptococcus pneumoniae). Since 2015, 2/7 patients were diagnosed with complement pathway dysregulation HUS and there were no cases of infectious etiology detected. Six of these patients received eculizumab. The global median follow-up was 6.5 years [3 months-19.8 years]. One patient died, seven had chronic kidney disease, four of whom underwent kidney transplantation, one relapsed, and seven had no sequelae. Conclusion: These results reflect the lack of infectious outbreaks in Portugal and the improvement on etiological identification since genetic testing was introduced. The majority of patients developed sequels and mortality was similar to that of other countries. HUS patients should be managed in centers with intensive care and pediatric nephrology with capacity for diagnosis, etiological investigation, and adequate treatment. Long-term follow-up is essential.

Resumo Introdução: Um melhor entendimento da fisiopatologia da síndrome hemolítico-urêmica (SHU) mudou significativamente seu tratamento e prognóstico. Este estudo teve como objetivo caracterizar condições clínicas, gravidade, manejo e desfechos de pacientes com SHU. Materiais e Métodos: Estudo retrospectivo de pacientes com SHU admitidos numa Unidade de Nefrologia Pediátrica entre 1996-2020. Foram coletados dados demográficos e clínicos sobre etiologia, gravidade, estratégias de tratamento, desfechos de pacientes. Resultados: 29 pacientes com SHU foram admitidos em nossa unidade, mas quatro foram excluídos. A idade mediana ao diagnóstico foi dois anos (2 meses-17 anos). Manifestações clínicas incluíram diarreia, vômitos, oligúria, hipertensão e febre. Durante a fase aguda, 14 pacientes (56%) necessitaram de terapia renal substitutiva. Identificou-se a etiologia infecciosa em sete pacientes (cinco Escherichia coli; dois Streptococcus pneumoniae). Desde 2015, 2/7 pacientes foram diagnosticados com SHU por desregulação da via do complemento e não foram detectados casos de etiologia infecciosa. Seis desses pacientes receberam eculizumab. A mediana global de acompanhamento foi 6,5 anos [3 meses-19,8 anos]. Um paciente faleceu, sete apresentaram doença renal crônica, sendo quatro submetidos a transplante renal, uma recidiva e sete sem sequelas. Conclusão: Estes resultados refletem a ausência de surtos infecciosos em Portugal e a melhoria na identificação etiológica desde que os testes genéticos foram introduzidos. A maioria dos pacientes desenvolveu sequelas e a mortalidade foi semelhante à de outros países. Pacientes com SHU devem ser manejados em centros com cuidados intensivos e nefrologia pediátrica com capacidade para diagnóstico, investigação etiológica e tratamento adequado. O acompanhamento alongo prazo é essencial.

Brazilian consensus for diagnosis, management and treatment of hereditary transthyretin amyloidosis with peripheral neuropathy: second edition / Consenso brasileiro para o diagnóstico, manejo e tratamento da polineuropatia amiloidótica familiar associada à transtirretina: segunda edição

Abstract Hereditary transthyretin amyloidosis with peripheral neuropathy (ATTRv-PN) is an autosomal dominant inherited sensorimotor and autonomic polyneuropathy with over 130 pathogenic variants identified in the TTR gene. Hereditary transthyretin amyloidosis with peripheral neuropathy is a disabling, progressive and life-threatening genetic condition that leads to death in ~ 10 years if untreated. The prospects for ATTRv-PN have changed in the last decades, as it has become a treatable neuropathy. In addition to liver transplantation, initiated in 1990, there are now at least 3 drugs approved in many countries, including Brazil, and many more are being developed. The first Brazilian consensus on ATTRv-PN was held in the city of Fortaleza, Brazil, in June 2017. Given the new advances in the area over the last 5 years, the Peripheral Neuropathy Scientific Department of the Brazilian Academy of Neurology organized a second edition of the consensus. Each panelist was responsible for reviewing the literature and updating a section of the previous paper. Thereafter, the 18 panelists got together virtually after careful review of the draft, discussed each section of the text, and reached a consensus for the final version of the manuscript.

Resumo Polineuropatia amiloidótica familiar associada a transtirretina (ATTRv-PN) é uma polineuropatia sensitivo-motora e autonômica hereditária autossômica dominante com mais de 130 variantes patogênicas já identificadas no gene TTR. A ATTRv-PN é uma condição genética debilitante, progressiva e que ameaça a vida, levando à morte em ~ 10 anos se não for tratada. Nas últimas décadas, a ATTRv-PN se tornou uma neuropatia tratável. Além do transplante de fígado, iniciado em 1990, temos agora 3 medicamentos modificadores de doença aprovados em muitos países, incluindo o Brasil, e muitas outras medicações estão em desenvolvimento. O primeiro consenso brasileiro em ATTRv-PN foi realizado em Fortaleza em junho de 2017. Devido aos novos avanços nesta área nos últimos 5 anos, o Departamento Científico de Neuropatias Periféricas da Academia Brasileira de Neurologia organizou uma segunda edição do consenso. Cada panelista ficou responsável por rever a literatura e atualizar uma parte do manuscrito. Finalmente, os 18 panelistas se reuniram virtualmente após revisão da primeira versão, discutiram cada parte do artigo e chegaram a um consenso sobre a versão final do manuscrito.

Hemolytic-uremic syndrome: 24 years' experience of a pediatric nephrology unit.

INTRODUCTION: A better understanding of hemolytic-uremic syndrome (HUS) pathophysiology significantly changed its treatment and prognosis. The aim of this study is to characterize the clinical features, severity, management, and outcomes of HUS patients. MATERIALS AND METHODS: Retrospective study of HUS patients admitted to a Pediatric Nephrology Unit between 1996 and 2020. Demographic and clinical data regarding etiology, severity, treatment strategies, and patient outcome were collected. RESULTS: Twenty-nine patients with HUS were admitted to our unit, but four were excluded. Median age at diagnosis was two years (2 months - 17 years). Clinical manifestations included diarrhea, vomiting, oliguria, hypertension, and fever. During the acute phase, 14 patients (56%) required renal replacement therapy. Infectious etiology was identified in seven patients (five Escherichia coli and two Streptococcus pneumoniae). Since 2015, 2/7 patients were diagnosed with complement pathway dysregulation HUS and there were no cases of infectious etiology detected. Six of these patients received eculizumab. The global median follow-up was 6.5 years [3 months-19.8 years]. One patient died, seven had chronic kidney disease, four of whom underwent kidney transplantation, one relapsed, and seven had no sequelae. CONCLUSION: These results reflect the lack of infectious outbreaks in Portugal and the improvement on etiological identification since genetic testing was introduced. The majority of patients developed sequels and mortality was similar to that of other countries. HUS patients should be managed in centers with intensive care and pediatric nephrology with capacity for diagnosis, etiological investigation, and adequate treatment. Long-term follow-up is essential.

Prenatal Diagnosis of Lissencephaly Associated with Biallelic Pathologic Variants in the COQ2 Gene.

Primary CoQ10 deficiency comprises several clinical phenotypes. Nevertheless, there are no reports so far of lissencephaly linked to CoQ10 deficiency. Lissencephaly is a developmental condition associated with defective neuronal migration which may be depicted on fetal neurosonography by persistence of a laminar pattern beyond 34 weeks and abnormal cortical sulcation. We report an index case of a male fetus diagnosed with abnormal lamination, characterized by the persistence of a laminar pattern during late pregnancy, following a normal second trimester scan. Post-natal whole exome sequencing revealed biallelic pathologic variants in the COQ2 gene which encodes an enzyme that is part of coenzyme Q10 (COQ10 or ubiquinone) pathway and is involved in the biosynthesis of CoQ, a redox carrier in the mitochondrial respiratory chain and a lipid-soluble antioxidant. This case underscores the heterogeneity of the prenatal phenotypic presentation of pathogenic variants in the COQ2, namely lissencephaly.

A deficiência primária de CoQ10 traduz-se numa variedade de fenótipos clínicos. Todavia, não existe até à data nenhuma descrição deste défice associado a lisencefalia. A lisencefalia consiste numa alteração do desenvolvimento cortical cerebral em que se verifica um defeito na migração neuronal, detetável na neurossonografia pela persistência de um padrão de laminação cerebral após as 34 semanas de gestação e por alterações nas circunvoluções corticais. Neste trabalho descreve-se o caso de um feto masculino com um padrão de laminação cerebral alterado, detetado na avaliação ecográfica do terceiro trimestre, após exame morfológico sem alterações. A sequenciação pós-natal do exoma revelou uma variante bialélica patológica do gene COQ2, que codifica uma enzima da via da coenzima Q10 (COQ10 ou ubiquinona), envolvida na biossíntese do CoQ, um transportador redox da cadeia respiratória mitocondrial e anti-oxidante lipossolúvel. Com este caso, destaca-se a heterogeneidade fenotípica pré-natal das variantes patogénicas no gene COQ2.

Interaction predictors of self-perception menstrual symptoms and influence of the menstrual cycle on physical performance of physically active women.

OBJECTIVE: To analyze the physical performance, self-perception menstrual symptoms, of physically active eumenorrheic women with endogenous ovarian cycle in two phases of the menstrual cycle. METHODS: Twenty-six women participated in the study (age 25.8 ± 3.9 years; height 1.64 ± 0.58 m; mass 64 ± 12.32 kg; menarche 11.69 ± 1.28 years). Assessments were performed in two phases of the menstrual cycle (MC), Early-Follicular Phase (FP) and Mid-Luteal Phase (LP), performance was assessed through total time to exhaustion (TTE), complete stages (CE), and final speed (FE), through a graded exercise test (GXT). Information on the participants' menstrual symptoms and their perceptions of the influence of MC on their performance were also collected. Data normality was assessed using the Shapiro-Wilk test. Paired analyses were conducted (t test or Wilcoxon) to examine the responses between the menstrual phases. The interaction analysis of symptom predictors was performed by multiple linear regression, with a significance level of p ≤ 0.05. RESULTS: There was no significant difference in physical performance between the phases during the GXT in TTE (mean difference 8.50; 95% CI - 11.99 to 42; p = 0.36). During FP, women with heavy flow had shorter performance in the GXT (t = - 2.5; p = 0.01), demonstrating an r2 = 0.32. In LP, for the women who reported not having the perception of the influence of the menstrual cycle on exercise, the total test time was longer (t = 2.55; p = 0.01), with an r2 = 0.45. CONCLUSION: There was no difference in physical performance between FP and LP. However, menstrual flow intensity and perception of cycle interference demonstrated a decrease in TTE.

Estado nutricional e segurança alimentar de famílias em vulnerabilidade social no município de Contagem, Minas Gerais, 2014 / Nutritional status and food security of socially vulnerable families in the municipality of Contagem, Minas Gerais, 2014

Este é um estudo transversal avaliando estado nutricional e insegurança alimentar em uma comunidade vulnerável de Contagem, região metropolitana de Belo Horizonte. Um total de 273 indivíduos de 67 famílias foram avaliados. Para a avaliação antropométrica, determinou-se o peso, a estatura, o índice de massa corporal, a circunferência da cintura e a razão cintura-estatura. A insegurança alimentar foi analisada por meio da Escala Brasileira de Insegurança Alimentar. As concentrações de colesterol total, triglicerídeos, glicose e albumina sérica também foram determinadas. Das 67 famílias avaliadas, 51% (n = 34) apresentaram insegurança alimentar, sendo 79,4% leve, 17,7% moderada e 2,9% grave. Em crianças e adolescentes, sobrepeso e obesidade foram diagnosticados em 9,3% (n = 4) e 19,5% (n=16), respectivamente. Entre os adultos, 34,1% (n = 42) foram classificados com sobrepeso, 27,6% (n = 34) com obesidade grau I e 59,3% (n = 73) apresentaram risco aumentado de doenças cardiovasculares. Nos idosos, o excesso de peso foi diagnosticado em 44,0% (n = 11) e 80,0% (n = 20) apresentaram risco aumentado para doenças cardiovasculares. Hiperglicemia, hipercolesterolemia e hipertrigliceridemia foram diagnosticadas em 17, 45 e 72% da população, respectivamente. Houve correlação positiva entre os parâmetros antropométricos e bioquímicos, com exceção da albumina e glicose, que apresentaram correlação negativa em crianças e adultos. Nosso estudo confirma o impacto da vulnerabilidade social na ocorrência de elevadas proporções de insegurança alimentar, ocasionando alta prevalência de sobrepeso e obesidade e risco aumentado para desordens cardiovasculares. Além disso, nossos achados endossam o uso de concentrações séricas de albumina como indicador de alterações no metabolismo da glicose.

This is a cross-sectional study evaluating nutritional status and food insecurity in a vulnerable community in Contagem, in the metropolitan region of Belo Horizonte. A total of 273 individuals from 67 families were evaluated. For the anthropometric assessment, weight, height, body mass index, waist circumference, and waist-to-height ratio were determined. Food insecurity was analyzed using the Brazilian Food Insecurity Scale. Total cholesterol, triglycerides, glucose, and serum albumin concentrations were also determined. Of the 67 families evaluated, 51% (n = 34) had food insecurity, of which 79.4% were mild, 17.7% were moderate, and 2.9% were severe. In children and adolescents, overweight and obesity were diagnosed in 9.3% (n = 4) and 19.5% (n = 16), respectively. Among adults, 34.1% (n = 42) were classified as overweight, 27.6% (n = 34) had grade I obesity, and 59.3% (n = 73) had an increased risk of cardiovascular disease. In the elderly, overweight was diagnosed in 44.0% (n = 11), and 80.0% (n = 20) had an increased risk for cardiovascular diseases. Hyperglycemia, hypercholesterolemia, and hypertriglyceridemia were diagnosed in 17, 45, and 72% of the population, respectively. There was a positive correlation between anthropometric and biochemical parameters, with the exception of albumin and glucose, which showed a negative correlation in children and adults. Our study confirms the impact of social vulnerability on the occurrence of high proportions of food insecurity, leading to a high prevalence of overweight and obesity and an increased risk for cardiovascular disorders. Furthermore, our findings support the use of serum albumin concentrations as an indicator of changes in glucose metabolism.

Controlling Macrophage Polarization to Modulate Inflammatory Cues Using Immune-Switch Nanoparticles.

The persistence of inflammatory mediators in tissue niches significantly impacts regenerative outcomes and contributes to chronic diseases. Interleukin-4 (IL4) boosts pro-healing phenotypes in macrophages (Mφ) and triggers the activation of signal transducer and activator of transcription 6 (STAT6). Since the IL4/STAT6 pathway reduces Mφ responsiveness to inflammation in a targeted and precise manner, IL4 delivery offers personalized possibilities to overcome inflammatory events. Despite its therapeutic potential, the limited success of IL4-targeted delivery is hampered by inefficient vehicles. Magnetically assisted technologies offer precise and tunable nanodevices for the delivery of cytokines by combining contactless modulation, high tissue penetration, imaging features, and low interference with the biological environment. Although superparamagnetic iron oxide nanoparticles (SPION) have shown clinical applicability in imaging, SPION-based approaches have rarely been explored for targeted delivery and cell programming. Herein, we hypothesized that SPION-based carriers assist in efficient IL4 delivery to Mφ, favoring a pro-regenerative phenotype (M2φ). Our results confirmed the efficiency of SPION-IL4 and Mφ responsiveness to SPION-IL4 with evidence of STAT6-mediated polarization. SPION-IL4-treated Mφ showed increased expression of M2φ associated-mediators (IL10, ARG1, CCL2, IL1Ra) when compared to the well-established soluble IL4. The ability of SPION-IL4 to direct Mφ polarization using sophisticated magnetic nanotools is valuable for resolving inflammation and assisting innovative strategies for chronic inflammatory conditions.

Magnetic Micellar Nanovehicles: Prospects of Multifunctional Hybrid Systems for Precision Theranostics.

Hybrid nanoarchitectures such as magnetic polymeric micelles (MPMs) are among the most promising nanotechnology-enabled materials for biomedical applications combining the benefits of polymeric micelles and magnetic nanoparticles within a single bioinstructive system. MPMs are formed by the self-assembly of polymer amphiphiles above the critical micelle concentration, generating a colloidal structure with a hydrophobic core and a hydrophilic shell incorporating magnetic particles (MNPs) in one of the segments. MPMs have been investigated most prominently as contrast agents for magnetic resonance imaging (MRI), as heat generators in hyperthermia treatments, and as magnetic-susceptible nanocarriers for the delivery and release of therapeutic agents. The versatility of MPMs constitutes a powerful route to ultrasensitive, precise, and multifunctional diagnostic and therapeutic vehicles for the treatment of a wide range of pathologies. Although MPMs have been significantly explored for MRI and cancer therapy, MPMs are multipurpose functional units, widening their applicability into less expected fields of research such as bioengineering and regenerative medicine. Herein, we aim to review published reports of the last five years about MPMs concerning their structure and fabrication methods as well as their current and foreseen expectations for advanced biomedical applications.

Controlling the fate of regenerative cells with engineered platelet-derived extracellular vesicles.

Extracellular vesicles (EVs) have emerged as cell-free nanotherapeutic agents for the potential treatment of multiple diseases and for tissue engineering and regenerative medicine strategies. Nevertheless, the field has typically relied on EVs derived from stem cells, the production of which in high quantities and high reproducibility is still under debate. Platelet-derived EVs were produced by a freeze-thaw method of platelet concentrates, a highly available clinical waste material. The aim of this study was to produce and thoroughly characterize platelet-derived EVs and understand their effects in adipose-tissue derived stem cells (hASCs), endothelial cells (HUVECs) and macrophages. Two different EV populations were obtained after differential centrifugation, namely small EVs (sEVs) and medium EVs (mEVs), which showed different size distributions and unique proteomic signatures. EV interaction with hASCs resulted in the modulation of the gene expression of markers related to their commitment toward different lineages. Moreover, mEVs showed higher angiogenic potential than sEVs, in a tube formation assay with HUVECs. Also, the EVs were able to modulate macrophage polarization. Altogether, these results suggest that platelet-derived EVs are promising candidates to be used as biochemical signals or therapeutic tools in tissue engineering and regenerative medicine approaches.

The impact of cryopreservation in signature markers and immunomodulatory profile of tendon and ligament derived cells.

Tendon and ligament (T/L) engineering strategies towards clinical practice have been challenged by a paucity of understanding in the identification and still poorly described characterization of cellular niches. Prospecting how resident cell populations behave in vitro, and how cryopreservation may influence T/ L-promoting factors, can provide insights into T/ L-cellular profiles for novel regenerative solutions. Therefore, we studied human T/ L-derived cells isolated from patellar tendons and cruciate ligaments as suitable cellular models to anticipate tendon and ligament niches responses for advanced strategies with predictive tenogenic and ligamentogenic value. Our results show that the crude populations isolated from tendon and ligament tissues hold a stem cell subset and share a similar behavior in terms of tenogenic/ligamentogenic commitment. Both T/ L-derived cells successfully undergo cryopreservation/thawing maintaining the tenogenic/ligamentogenic profiles. The major differences between cryopreserved and fresh populations were observed at the gene expression of MKX, SCX, and TNMD as well as at the protein levels of collagen type I and III, in which cells from tendon origin (hTDCs) evidence increased values in comparison to the ones from ligament (hLDCs, p < 0.05). In addition, low-temperature storage was shown to potentiate an immunomodulatory profile of cells, especially in hTDCs leading to an increase in the gene expression of the anti-inflammatory factors IL-4 and IL-10 (p < 0.05), as well as in the protein secretion of IL-10 (p < 0.01) and IL-4 (p < 0.001). Overall, the outcomes highlight the relevance of the cryopreserved T/ L-derived cells and their promising immunomodulatory cues as in vitro models for investigating cell-mediated mechanisms driving tissue healing and regeneration.

Physical and Chemical Properties of Waste Foundry Exhaust Sand for Use in Self-Compacting Concrete.

The reuse of waste in civil construction brings environmental and economic benefits. However, for these to be used in concrete, it is necessary a previous evaluation of their physical and chemical characteristics. Thus, this study aimed to characterize and analyze the waste foundry exhaust sand (WFES) for use in self-compacting concrete (SCC). Foundry exhaust sand originates from the manufacturing process of sand molds and during demolding of metal parts. It is a fine sand rich in silica in the form of quartz collected by baghouse filter. Characterization of WFES was conducted through laser granulometry, scanning electron microscopy (SEM) in the energy dispersive spectroscopy (EDS) mode, X-ray diffraction (XRD), X-ray fluorescence (XRF), Fourier transform infrared spectroscopy (FTIR), thermogravimetry (TG) and derivative thermogravimetry (DTG) techniques. The waste was classified as non-hazardous and non-inert, with physical and chemical properties suitable for use in SCC composition, as fine aggregate or mineral addition. Five mixtures of SCC were developed, in order to determine the waste influence in both fresh and hardened concrete. The properties in the fresh state were reached. There was an increase in compressive strength and sulfate resistance, a decrease in water absorption of self-compacting concrete by incorporating WFES as 30% replacement.