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Depression is a prevalent chronic psychiatric disorder with a growing impact on global health. Current treatments often fail to achieve full remission, highlighting the need for alternative therapeutic strategies. Mesenchymal stem cells (MSCs) have attracted significant interest for their therapeutic potential in neuropsychiatric disorders, primarily due to their capacity to target neuroinflammation. This study aimed to investigate if extracellular vesicles derived from human umbilical MSCs (hucMSCs) promote behavioral beneficial actions in a rat model of chronic unpredictable mild stress (CUMS). We show that a single dose of hucMSCs or their derived EVs (hucMSC-EVs) via the tail vein alleviated depressive-like behavior in rats, reduced markers of neuroinflammation, reduced pro-inflammatory cytokines (IL-1β and TNF-α), and increased the number and dendritic complexity of DCX-positive cells in the dentate gyrus. Proteomic analysis of EVs revealed the presence of proteins involved in modulation of inflammatory processes and cell activation. Our study demonstrates EVs derived from hucMSCs can effectively mitigate depressive symptoms by modulating neuroinflammatory pathways and enhancing neurogenesis. These findings support further exploration of MSC-derived EVs as a novel therapeutic option for neuropsychiatric disorders., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Waste milk (WM) is commonly used in calf feeding to reduce rearing costs; however, its effects on the innate immune response remain unexplored. Therefore, this study aimed to evaluate the effects of WM on the innate immune response and inflammatory profile of pre-weaned dairy calves. Thirty male Holstein calves were assigned to receive pasteurized waste milk (PWM), saleable milk (SM), and WM (n = 10 in each group). Blood samples were collected on D7, D21, D35, D49, and D63 (days of life) to assess the white blood cell (WBC) count, phagocytic activity of polymorphonuclear cells (PMN), and nitric oxide (NO) production by monocyte-derived macrophages, in addition to the measurement of oxidative stress biomarkers and haptoglobin concentration. A trend towards a higher occurrence of respiratory disease was detected in calves that received WM, followed by PWM. A group effect (P = 0.00) was observed in absolute monocyte values, with higher values found in the WM group. Only the TBARS concentration showed a group × time interaction among all oxidative stress biomarkers, with the highest mean found in calves receiving WM, followed by those receiving PWM and SM. Elevated TBARS concentrations indicated higher lipid peroxidation, which may have resulted from the accumulation of reactive oxygen species (ROS) due to immune challenges from ingesting pathogens present in WM. Haptoglobin concentration was unaffected. WM promoted lipid peroxidation and antioxidant enzyme activity, suggesting a pro-inflammatory effect. The time-effects of PMN phagocytosis reflected the development of the immune system in neonatal calves, which is consistent with previous studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Background: Despite many years of investigation into mesenchymal stem cells (MSCs) and their potential for treating inflammatory conditions such as COVID-19, clinical outcomes remain variable due to factors like donor variability, different tissue sources, and diversity within MSC populations. Variations in MSCs' secretory and proliferation profiles, and their proteomic and transcriptional characteristics significantly influence their therapeutic potency, highlighting the need for enhanced characterization methods to better predict their efficacy. This study aimed to evaluate the biological characteristics of MSCs from different tissue origins, selecting the most promising line for further validation in a K18-hACE2 mouse model of SARS-CoV-2 infection., Methods: We studied nine MSC lines sourced from either bone marrow (hBMMSC), dental pulp (hDPMSC), or umbilical cord tissue (hUCMSC). The cells were assessed for their proliferative capacity, immunophenotype, trilineage differentiation, proteomic profile, and in vitro immunomodulatory potential by co-culture with activated lymphocytes. The most promising MSC line was selected for further experimental validation using the K18-hACE2 mouse model of SARS-CoV-2 infection., Results: The analyzed cells met the minimum criteria for defining MSCs, including the expression of surface molecules and differentiation capacity, showing genetic stability and proliferative potential. Proteomic analysis revealed distinct protein profiles that correlate with the tissue origin of MSCs. The immunomodulatory response exhibited variability, lacking a discernible pattern associated with their origin. In co-culture assays with lymphocytes activated with anti-CD3/CD28 beads, all MSC lines demonstrated the ability to inhibit TNF-α, to induce TGF-β and Indoleamine 2,3-dioxygenase (IDO), with varying degrees of inhibition observed for IFN-γ and IL-6, or induction of IL-10 expression. A module of proteins was found to statistically correlate with the potency of IL-6 modulation, leading to the selection of one of the hUCMSCs as the most promising line. Administration of hUCMSC to SARS-CoV-2-infected K18 mice expressing hACE2 was effective in improving lung histology and modulating of a panel of cytokines., Conclusions: Our study assessed MSCs derived from various tissues, uncovering significant variability in their characteristics and immunomodulatory capacities. Particularly, hUCMSCs demonstrated potential in mitigating lung pathology in a SARS-CoV-2 infection model, suggesting their promising therapeutic efficacy., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Ethics Committee of Hospital São Rafael (CAAE: 09803819.30000.0048, titled: “Avaliação do potencial terapêutico de celulas-tronco mesenquimais para uso clínico”, date of approval: 04/02/2019). All tissue donors or their legal guardians gave written informed consent for participation and publication of this study. The study involving mice was approved by the Institutional Animal Care and Use Committee (IACUC) of the Federal University of Minas Gerais (Comissão de Ética no Uso de Animais – CEUA). The project, titled ‘Implementação e caracterização de modelo experimental de COVID-19 em camundongos transgênicos K18-hACE2,’ was approved on September 13, 2021, under protocol number 191/2021. Name of the institutional approval committee or unit: Aprovado pela Comissão de Ética no uso de animais (CEUA) da Universidade Federal de Minas Gerais. The approval number: CEUA 191/2021. Date of approval: 13/09/2021. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Objective: Spinal cord injury (SCI) is a serious condition that can lead to partial or complete paraplegia or tetraplegia. Currently, there are few therapeutic options for these conditions, which are mainly directed toward the acute phase, such as surgical intervention and high-dose steroid administration. Mesenchymal stromal cells (MSC) have been shown to improve neurological function following spinal cord injury. The aim of the study was to evaluate the safety, feasibility, and potential efficacy of MSC transplantation in patients with cervical traumatic SCI., Methods: We included seven subjects with chronic traumatic SCI (> 1 year) at the cervical level, classified as American Spinal Cord Injury Association impairment scale (AIS) grade A. Subjects received two doses of autologous bone marrow derived MSC, the first by direct injection into the lesion site after hemilaminectomy and the second three months later by intrathecal injection. Neurologic evaluation, spinal magnetic resonance imaging (MRI), urodynamics, and life quality questionnaires were assessed before and after treatment., Results: Cell transplantation was safe without severe or moderate adverse effects, and the procedures were well tolerated. Neurological evaluation revealed discrete improvements in sensitivity below the lesion level, following treatment. Five subjects showed some degree of bilateral sensory improvement for both superficial and deep mechanical stimuli compared to the pretreatment profile. No significant alterations in bladder function were observed during this study., Conclusion: Transplantation of autologous MSC in patients with chronic cervical SCI is a safe and feasible procedure. Further studies are required to confirm the efficacy of this therapeutic approach., Clinical Trial Registration: https://clinicaltrials.gov/study/NCT02574572, identifier NCT02574572., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Macêdo, de Freitas Souza, Villarreal, Silva, da Silva, de Souza, da Silva Paixão, da Rocha Bezerra, da Silva Moura Costa, Brazão, Marins Filho, Matos, dos Santos and Soares.)

Plasmonic catalysis has been employed to enhance molecular transformations under visible light excitation, leveraging the localized surface plasmon resonance (LSPR) in plasmonic nanoparticles. While plasmonic catalysis has been employed for accelerating reaction rates, achieving control over the reaction selectivity has remained a challenge. In addition, the incorporation of catalytic components into traditional plasmonic-catalytic antenna-reactor nanoparticles often leads to a decrease in optical absorption. To address these issues, this study focuses on the synthesis of bimetallic core@shell Au@AuPd nanoparticles (NPs) with ultralow loadings of palladium (Pd) into gold (Au) NPs. The goal is to achieve NPs with an Au core and a dilute alloyed shell containing both Au and Pd, with a low Pd content of around 10 atom %. By employing the (photo)electrocatalytic nitrite reduction reaction (NO 2 RR) as a model transformation, experimental and theoretical analyses show that this design enables enhanced catalytic activity and selectivity under visible light illumination. We found that the optimized Pd distribution in the alloyed shell allowed for stronger interaction with key adsorbed species, leading to improved catalytic activity and selectivity, both under no illumination and under visible light excitation conditions. The findings provide valuable insights for the rational design of antenna-reactor plasmonic-catalytic NPs with controlled activities and selectivity under visible light irradiation, addressing critical challenges to enable sustainable molecular transformations.

Background Aims: Extracellular vesicles (EVs) represent a new axis of intercellular communication that can be harnessed for therapeutic purposes, as cell-free therapies. The clinical application of mesenchymal stromal cell (MSC)-derived EVs, however, is still in its infancy and faces many challenges. The heterogeneity inherent to MSCs, differences among donors, tissue sources, and variations in manufacturing conditions may influence the release of EVs and their cargo, thus potentially affecting the quality and consistency of the final product. We investigated the influence of cell culture and conditioned medium harvesting conditions on the physicochemical and proteomic profile of human umbilical cord MSC-derived EVs (hUCMSC-EVs) produced under current good manufacturing practice (cGMP) standards. We also evaluated the efficiency of the protocol in terms of yield, purity, productivity, and expression of surface markers, and assessed the biodistribution, toxicity and potential efficacy of hUCMSC-EVs in pre-clinical studies using the LPS-induced acute lung injury model., Methods: hUCMSCs were isolated from a cord tissue, cultured, cryopreserved, and characterized at a cGMP facility. The conditioned medium was harvested at 24, 48, and 72 h after the addition of EV collection medium. Three conventional methods (nanoparticle tracking analysis, transmission electron microscopy, and nanoflow cytometry) and mass spectrometry were used to characterize hUCMSC-EVs. Safety (toxicity of single and repeated doses) and biodistribution were evaluated in naive mice after intravenous administration of the product. Efficacy was evaluated in an LPS-induced acute lung injury model., Results: hUCMSC-EVs were successfully isolated using a cGMP-compliant protocol. Comparison of hUCMSC-EVs purified from multiple harvests revealed progressive EV productivity and slight changes in the proteomic profile, presenting higher homogeneity at later timepoints of conditioned medium harvesting. Pooled hUCMSC-EVs showed a non-toxic profile after single and repeated intravenous administration to naive mice. Biodistribution studies demonstrated a major concentration in liver, spleen and lungs. HUCMSC-EVs reduced lung damage and inflammation in a model of LPS-induced acute lung injury., Conclusions: hUCMSC-EVs were successfully obtained following a cGMP-compliant protocol, with consistent characteristics and pre-clinical safety profile, supporting their future clinical development as cell-free therapies., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

The hydrogen evolution and nitrite reduction reactions are key to producing green hydrogen and ammonia. Antenna-reactor nanoparticles hold promise to improve the performances of these transformations under visible-light excitation, by combining plasmonic and catalytic materials. However, current materials involve compromising either on the catalytic activity or the plasmonic enhancement and also lack control of reaction selectivity. Here, we demonstrate that ultralow loadings and non-uniform surface segregation of the catalytic component optimize catalytic activity and selectivity under visible-light irradiation. Taking Pt-Au as an example we find that fine-tuning the Pt content produces a 6-fold increase in the hydrogen evolution compared to commercial Pt/C as well as a 6.5-fold increase in the nitrite reduction and a 2.5-fold increase in the selectivity for producing ammonia under visible light excitation relative to dark conditions. Density functional theory suggests that the catalytic reactions are accelerated by the intimate contact between nanoscale Pt-rich and Au-rich regions at the surface, which facilitates the formation of electron-rich hot-carrier puddles associated with the Pt-based active sites. The results provide exciting opportunities to design new materials with improved photocatalytic performance for sustainable energy applications., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Maternal status during the transition period can significantly impact the health and performance of Holstein dairy calves, with lasting effects on various variables. However, the relationship between maternal late gestation metabolic status, seasonality, and their impact on offspring remains unclear. This study aimed to assess the influence of maternal variables at calving on the performance, metabolism, and immunity of 28 dairy calves during their first month of life. Blood samples were collected from 28 Holstein cows at calving. Median results for maternal variables including non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), glucose, total protein (TP), albumin, triglycerides (TG), total cholesterol (TC), haptoglobin (Hp), body weight (BW), and body condition score (BCS) were determined. These median values served as a basis for categorizing the offspring into two groups based on their dams' high or low degree of each maternal variable. Additionally, calves were categorized by the season of birth (Spring vs. Winter), with 14 in each. Blood samples were collected from the calves at birth and on days 1, 7, 14, and 28 to assess IgG, biochemical parameters, and haptoglobin concentration. Reactive oxygen species (ROS) production by polymorphonuclear cells stimulated by various agents was also evaluated. Clinical assessments were conducted for diarrhea and bovine respiratory disease frequencies. Despite the overall health of the cows, differences were observed in the calves between maternal groups. Heavier cows with high maternal BCS tended to have larger offspring, while high maternal BCS was associated with increased diarrhea prevalence. Low maternal BCS resulted in a stronger innate immune response, indicated by higher ROS production. Calves from cows experiencing metabolic changes during calving displayed elevated Hp concentrations. Spring-born calves were larger but had lower serum IgG concentration and reduced innate immune response compared to winter-born calves. Additionally, spring-born calves exhibited higher Hp and increased diarrhea prevalence on day 28. These findings underscore the importance of the prenatal period in determining neonatal health and suggest further research to elucidate the long-term clinical implications of maternal effects on offspring health and growth. Investigating offspring constituents later in life can provide insight into the persistence of maternal effects over time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Santos, Santarosa, Dal Más, Silva, Guirro and Gomes.)

Background: The development and state of innate immune cell function during the first 90 days of life in dairy calves have not been fully described., Objective: This transversal study attempted to examine the changes that occur in circulating blood cells and the innate immune response in healthy calves from birth to 89 days of age., Methods: Healthy Holstein calves represent three windows of development, G1 from 1 to 7 days old (n = 26), G2 from 30 to 40 days old (n = 28), and G3 from 60 to 89 days old (n = 36) were sampled once each from a single herd. A few biomarkers of the general health and innate and inflammatory immune responses were measured., Results: The youngest calves had the lowest red blood cell (RBC) counts, cell hemoglobin concentration means (CHCMs), red cell distribution widths (RDWs), and cell hemoglobin contents of mature red blood cells (CHm) compared with the other groups. They also had the lowest iron concentrations and highest intracellular myeloperoxidase indices. However, white blood cell (WBC) and lymphocyte concentrations gradually increased from G1 to G3. G2 calves had the lowest serum protein concentrations and highest number of innate immune cells compared with the other groups. Calves were able to mount phagocytic and ROS responses from birth., Conclusions: The physiologic responses of circulating blood cells and innate immune responses in dairy calves are shown according to age. Neonates had limitations in several RBC and WBC indices and immunologic responses that would likely impact overall vigor and health. Fortunately, these limitations resolve by 90 days of age., (© 2022 American Society for Veterinary Clinical Pathology.)

Objective: To evaluate the contributions of educational technologies used during the guidelines for sputum collection from pulmonary tuberculosis., Method: Systematic review guided by Preferred Reporting items for Systematic Reviews with protocol registered in the database International Prospective Register of Systematic Reviews, with number CRD42020208162. The search was performed in the Cinahl, Scopus, PubMed, Web of Science, Embase, Lilacs, CENTRAL, CAPES, Proquest, OpenGrey databases and manual search in the reference list. The search, selection of studies, data extraction, and methodological evaluation using the Cochrane Risk-of-Bias tool were performed by two independent reviewers., Results: A total of 2,488 studies were evidenced, with seven being selected and analyzed, of which four used structured lectures; three, educational booklet; and one, an educational video, used alone or together, impacting the bacteriological confirmation of tuberculosis. The studies had a low risk of bias., Conclusion: Scientific evidence has shown that educational technologies contribute to increasing the quality, volume, and appearance of the sputum sample, which improves the bacteriological confirmation of the disease.

Background: The patients with coronavirus disease 2019 (COVID-19) associated with severe acute respiratory distress syndrome (ARDS) may require prolonged mechanical ventilation which often results in lung fibrosis, thus worsening the prognosis and increasing fatality rates. A mesenchymal stromal cell (MSC) therapy may decrease lung inflammation and accelerate recovery in COVID-19. In this context, some studies have reported the effects of MSC therapy for patients not requiring invasive ventilation or during the first hours of tracheal intubation. However, this is the first case report presenting the reduction of not only lung inflammation but also lung fibrosis in a critically ill long-term mechanically ventilated patient with COVID-19. Case Presentation: This is a case report of a 30-year-old male patient with COVID-19 under invasive mechanical ventilation for 14 days in the intensive care unit (ICU), who presented progressive clinical deterioration associated with lung fibrosis. The symptoms onset was 35 days before MSC therapy. The patient was treated with allogenic human umbilical-cord derived MSCs [5 × 10 7 (2 doses 2 days interval)]. No serious adverse events were observed during and after MSC administration. After MSC therapy, PaO 2 /FiO 2 ratio increased, the need for vasoactive drugs reduced, chest CT scan imaging, which initially showed signs of bilateral and peripheral ground-glass, as well as consolidation and fibrosis, improved, and the systemic mediators associated with inflammation decreased. Modulation of the different cell populations in peripheral blood was also observed, such as a reduction in inflammatory monocytes and an increase in the frequency of patrolling monocytes, CD4+ lymphocytes, and type 2 classical dendritic cells (cDC2). The patient was discharged 13 days after the cell therapy. Conclusions: Mesenchymal stromal cell therapy may be a promising option in critically ill patients with COVID-19 presenting both severe lung inflammation and fibrosis. Further clinical trials could better assess the efficacy of MSC therapy in critically ill patients with COVID-19 with lung fibrosis associated with long-term mechanical ventilation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Silva, Pinheiro, Gobatto, Passos, Paredes, França, Nonaka, Barreto-Duarte, Araújo-Pereira, Tibúrcio, Cruz, Martins, Andrade, Castro-Faria-Neto, Rocco and Souza.)

Despite several papers describing the oscillatory methanol electrooxidation reaction (OMOR) catalyzed by polycrystalline Pt, these dynamic instabilities are less explored on single crystalline surfaces. Herein, we observed and mapped for the first time the OMOR on Pt(111) in non-adsorbing anion solutions as well as in the presence of small amounts of sulfate anions. Period 1 oscillations with oscillation frequencies from 1.2 to 2.0 Hz were observed for methanol concentrations higher than 1.0 M, with no evolution to more complex patterns. These oscillations occur in the potential range in which PtOH is partially covering the surface without irreversible oxidation processes. Small changes in both the mean potential ( E m ) and the poisoning rate along the time-series were observed, the so-called drift , and were explained in terms of the accumulation of intermediates at the interface. The presence of sulfate strongly inhibits the OMOR, and the results are discussed in terms of sulfate adlayer formation on {111} domains.

The COVID-19 pandemic, caused by the rapid global spread of the novel coronavirus (SARS-CoV-2), has caused healthcare systems to collapse and led to hundreds of thousands of deaths. The clinical spectrum of COVID-19 is not only limited to local pneumonia but also represents multiple organ involvement, with potential for systemic complications. One year after the pandemic, pathophysiological knowledge has evolved, and many therapeutic advances have occurred, but mortality rates are still elevated in severe/critical COVID-19 cases. Mesenchymal stromal cells (MSCs) can exert immunomodulatory, antiviral, and pro-regenerative paracrine/endocrine actions and are therefore promising candidates for MSC-based therapies. In this review, we discuss the rationale for MSC-based therapies based on currently available preclinical and clinical evidence of safety, potential efficacy, and mechanisms of action. Finally, we present a critical analysis of the risks, limitations, challenges, and opportunities that place MSC-based products as a therapeutic strategy that may complement the current arsenal against COVID-19 and reduce the pandemic's unmet medical needs., (© 2021. The Author(s).)

This research communication presents an automatic method for the counting of somatic cells in buffalo milk, which includes the application of a fuzzy clustering method and image processing techniques (somatic cell count with fuzzy clustering and image processing|, SCCFCI). Somatic cell count (SCC) in milk is the main biomarker for assessing milk quality and it is traditionally performed by exhaustive methods consisting of the visual observation of cells in milk smears through a microscope, which generates uncertainties associated with human interpretation. Unlike other similar works, the proposed method applies the Fuzzy C-Means (FCM) method as a preprocessing step in order to separate the images (objects) of the cells into clusters according to the color intensity. This contributes signficantly to the performance of the subsequent processing steps (thresholding, segmentation and recognition/identification). Two methods of thresholding were evaluated and the Watershed Transform was used for the identification and separation of nearby cells. A detailed statistical analysis of the results showed that the SCCFCI method is able to provide results which are consistent with those obtained by conventional counting. This method therefore represents a viable alternative for quality control in buffalo milk production.

Human-induced pluripotent stem cell (hiPSC) CBTCi001-A line was generated from a healthy 30-year old male dermal fibroblasts using non-integrative reprogramming method using episomal-based plasmids expressing OCT4, SOX2, KLF4, and MYCL. Characterization of CBTCi001-A was confirmed by the expression of typical markers of pluripotency and differentiation potential in vitro., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

Autism spectrum disorders (ASDs) are a group of diseases that affect social interaction, communication and behavior. Molecular mechanisms involved in the pathogenesis of ASDs are complex due to genetic heterogeneity. Recently, pathogenic variants of SCN2A have been strongly associated with ASDs. Here, we generated iPSCs from a patient with ASD and a heterozygous nonsense mutation in SCN2A, by reprogramming mesenchymal stromal cells with non-integrating vectors. The generated iPSC line expresses pluripotency markers, presents a normal karyotype and is able to differentiate into the three germ layers. This iPSC line is a useful tool for modeling ASD and drug screening studies., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Mesenchymal stem cells (MSC) are promising tools in the fields of cell therapy and regenerative medicine. In addition to their differentiation potential, MSC have the ability to secrete bioactive molecules that stimulate tissue regeneration. Thus, the overexpression of cytokines and growth factors may enhance the therapeutic effects of MSC. Here we generated and characterized mouse bone marrow MSC lines overexpressing hG-CSF or hIGF-1. MSC lines overexpressing hG-CSF or hIGF-1 were generated through lentiviral vector mediated gene transfer. The expression of hG-CSF or hIGF-1 genes in the clones produced was quantified by qRT-PCR, and the proteins were detected in the cell supernatants by ELISA. The cell lines displayed cell surface markers and differentiation potential into adipocytes, osteocytes and chondrocytes similar to the control MSC cell lines, indicating the conservation of their phenotype even after genetic modification. IGF-1 and G-CSF transgenic cells maintained immunosuppressive activity. Finally, we performed a comparative gene expression analysis by qRT-PCR array in the cell lines expressing hIGF-1 and hG-CSF when compared to the control cells. Our results demonstrate that the cell lines generated may be useful tools for cell therapy and are suitable for testing in disease models.

Background Aims: The potential of cell therapies to improve neurological function in subjects with spinal cord injury (SCI) is currently under investigation. In this context, the choice of cell type, dose, route and administration regimen are key factors. Mesenchymal stromal cells (MSCs) can be easily obtained, expanded and are suitable for autologous transplantation. Here we conducted a pilot study that evaluated safety, feasibility and potential efficacy of intralesional MSCs transplantation performed through image-guided percutaneous injection, in subjects with chronic complete SCI., Methods: Five subjects with chronic traumatic SCI (>6 months), at thoracic level, classified as American Spinal Cord Injury Association impairment scale (AIS) grade A, complete injury, were included. Somatosensory evoked potentials (SSEP), spinal magnetic resonance imaging (MRI) and urodynamics were assessed before and after treatment. Autologous MSCs were injected directly into the lesion site through percutaneous injection guided by computerized tomography (CT)., Results: Tomography-guided percutaneous cell transplantation was a safe procedure without adverse effects. All subjects displayed improvements in spinal cord independence measure (SCIM) scores and functional independence measure (FIM), mainly due to improvements in bowel movements and regularity. Three subjects showed improved sensitivity to tactile stimulation. Two subjects improved AIS grade to B, incomplete injury, although this was sustained in only one of them during the study follow-up., Conclusion: Autologous bone marrow MSC transplantation, performed through CT-guided percutaneous injection, was shown to be safe and feasible. Further studies are required to demonstrate efficacy of this therapeutic scheme., (Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Chronic Chagas disease cardiomyopathy, caused by Trypanosoma cruzi infection, is a major cause of heart failure in Latin America. Galectin-3 (Gal-3) has been linked to cardiac remodeling and poor prognosis in heart failure of different etiologies. Herein, we investigated the involvement of Gal-3 in the disease pathogenesis and its role as a target for disease intervention. Gal-3 expression in mouse hearts was evaluated during T. cruzi infection by confocal microscopy and flow cytometry analysis, showing a high expression in macrophages, T cells, and fibroblasts. In vitro studies using Gal-3 knockdown in cardiac fibroblasts demonstrated that Gal-3 regulates cell survival, proliferation, and type I collagen synthesis. In vivo blockade of Gal-3 with N-acetyl-d-lactosamine in T. cruzi-infected mice led to a significant reduction of cardiac fibrosis and inflammation in the heart. Moreover, a modulation in the expression of proinflammatory genes in the heart was observed. Finally, histological analysis in human heart samples obtained from subjects with Chagas disease who underwent heart transplantation showed the expression of Gal-3 in areas of inflammation, similar to the mouse model. Our results indicate that Gal-3 plays a role in the pathogenesis of experimental chronic Chagas disease, favoring inflammation and fibrogenesis. Moreover, by demonstrating Gal-3 expression in human hearts, our finding reinforces that this protein could be a novel target for drug development for Chagas cardiomyopathy., (Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Therapies based on transplantation of mesenchymal stromal cells (MSC) hold promise for the management of inflammatory disorders. In chronic Chagas disease cardiomyopathy (CCC), caused by chronic infection with Trypanosoma cruzi , the exacerbated immune response plays a critical pathophysiological role and can be modulated by MSC. Here, we investigated the role of galectin-3 (Gal-3), a beta-galactoside-binding lectin with several actions on immune responses and repair process, on the immunomodulatory potential of MSC. Gal-3 knockdown in MSC did not affect the immunophenotype or differentiation potential. However, Gal-3 knockdown MSC showed decreased proliferation, survival, and migration. Additionally, when injected intraperitoneally into mice with CCC, Gal-3 knockdown MSC showed impaired migration in vivo. Transplantation of control MSC into mice with CCC caused a suppression of cardiac inflammation and fibrosis, reducing expression levels of CD45, TNF α , IL-1 β , IL-6, IFN γ , and type I collagen. In contrast, Gal-3 knockdown MSC were unable to suppress the immune response or collagen synthesis in the hearts of mice with CCC. Finally, infection with T. cruzi demonstrated parasite survival in wild-type but not in Gal-3 knockdown MSC. These findings demonstrate that Gal-3 plays a critical role in MSC survival, proliferation, migration, and therapeutic potential in CCC.

This study reports on the design, synthesis and antiparasitic activity of three new semi-synthetic naphthoquinones structurally related to the naturally-occurring lapachol and lapachone. Of the compounds tested, 3-(3-methylbut-1-en-1-yl)-1,4-dioxo-1,4-dihydronaphthalen-2-yl acetate (1) was the most active against Plasmodium falciparum among both natural and semi-synthetic naphthoquinones, showing potent and selective activity. Compound 1 was able to reduce the in vitro parasite burden, in vitro parasite cell cycle, as well as the blood parasitemia in Plasmodium berghei-infected mice. More importantly, infection reduction under compound 1-treatment was achieved without exhibiting mouse genotoxicity. Regarding the molecular mechanism of action, this compound inhibited the hemozoin crystal formation in P. falciparum treated cells, and this was further confirmed by observing that it inhibits the β-hematin polymerization process similarly to chloroquine. Interestingly, this compound did not affect either mitochondria structure or cause DNA fragmentation in parasite treated cells. In conclusion, we identified a semi-synthetic antimalarial naphthoquinone closely related to isolapachol, which had stronger antimalarial activity than lapachol.

The objective of this study was to evaluate the effectiveness of a sensorimotor training in patients with rheumatoid arthritis on the improvement of functional skills and quality of life, a double-blinded, prospective, randomized controlled trial. One hundred two participants with rheumatoid arthritis were selected. After the baseline evaluation, the participants were randomized to two different groups: sensorimotor group (2 sessions per week, 30-50 min each session, besides continuing taking the same drugs as the control group) and control group (control group was only submitted to the clinical drug treatment with Methotrexate, Leflunomide and/or Prednisone (5 mg), being then evaluated 4 months later). Functional capacity [Health Assessment Questionnaire (HAQ) and Timed Up & Go Test (TU>)], Balance and Gait (Berg Balance Scale (BBS) and Tinetti Test) and Quality of Life (Short Form Health Survey-SF-36). The study had been concluded with ninety-one participants, and a statistically significant improvement was found in all variables assessed: HAQ (P < .01), TU> (P < .01), BBS (P < .01), Tinetti Test (P < .01) and improvement in the subscales of SF-36 (P < .01) in the sensorimotor group in comparison with the baseline evaluation and control group. No significant difference was found related to the pre- and post-evaluation in the control group. Therefore, the sensorimotor training is effective in the improvement of the functional capacity and quality of life of patients with rheumatoid arthritis.

Objectives: To investigate the effect of 8 weeks of NMES + Ex (neuromuscular electrical stimulation combined with exercises) on pain and functional improvement in patients with knee osteoarthritis (OA) compared to exercise (Ex) alone., Design: Randomized controlled trial., Setting: A specialty outpatient clinic., Participants: Patients (N = 100; women = 86, men = 14; age range, 50-75 years) with knee OA., Interventions: Participants were randomly assigned to NMES + Ex or Ex group., Outcome Measures: Numerical Rating Scale 0 to 10 (NRS) and the Timed Up and Go (TUG) test were the primary outcomes. The secondary outcomes used were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)., Results: Following the interventions, a statistically significant improvement in both groups was observed in all outcomes assessed. For the comparison between the groups, no statistically significant difference was found between the NMES + Ex and the Ex groups in NRS (P = 0.52), TUG test (P = 0.12), and aspects of WOMAC: pain (P = 0.26), function (P = 0.23), and stiffness (P = 0.63)., Conclusion: THE addition of NMES to exercise did not improve the outcomes assessed in knee OA patients. This study was registered at the Australian Clinical Trials Registry (ACTRN012607000357459).