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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.