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1.
Antibiotics (Basel) ; 13(3)2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38534708

ABSTRACT

Oral infections occur due to contact between biofilm rich in Candida albicans formed on the inner surface of complete dentures and the mucosa. This study investigated historical advances in the prevention and treatment of oral mucosal infection and identified gaps in the literature. Bibliographic research was conducted, looking at PubMed, Embase, Web of Science, and Scopus, where 935 articles were found. After removing duplicates and excluding articles by reading the title and abstract, 131 articles were selected for full reading and 104 articles were included. Another 38 articles were added from the gray literature. This review followed the PRISMA-ScR guidelines. The historical period described ranges from 1969 to 2023, in which, during the 21st century, in vitro and in vivo studies became more common and, from 2010 to 2023, the number of randomized controlled trials increased. Among the various approaches tested are the incorporation of antimicrobial products into prosthetic materials, the improvement of oral and denture hygiene protocols, the development of synthetic and natural products for the chemical control of microorganisms, and intervention with local or systemic antimicrobial agents. Studies report good results with brushing combined with sodium hypochlorite, and new disinfectant solutions and products incorporated into prosthetic materials are promising.

2.
Cytotherapy ; 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38506771

ABSTRACT

BACKGROUND & AIMS: Cell therapies based on mesenchymal stromal cells (MSCs) have gained an increasing therapeutic interest in the context of multiple disorders. Nonetheless, this field still faces important challenges, particularly concerning suitable manufacturing platforms. Here, we aimed at establishing a scalable culture system to expand umbilical cord-derived Wharton's jelly MSC (MSC(WJ)) and their derived extracellular vesicles (EVs) by using dissolvable microcarriers combined with xeno(geneic)-free culture medium. METHODS: MSC(WJ) isolated from three donors were cultured at a starting density of 1 × 106 cells per spinner flask, i.e., 2.8 × 103 cells per cm2 of dissolvable microcarrier surface area. After a 6-day expansion period of MSC(WJ), extracellular vesicles (EVs) were produced for 24 h. RESULTS: Taking advantage of an intermittent agitation regimen, we observed high adhesion rates to the microcarriers (over 90% at 24 h) and achieved 15.8 ± 0.7-fold expansion after 6 days of culture. Notably, dissolution of the microcarriers was achieved through a pectinase-based solution to recover the cell product, reducing the hurdles of downstream processing. MSC identity was validated by detecting the characteristic MSC immunophenotype and by multilineage differentiation assays. Considering the growing interest in MSC-derived EVs, which are known to be mediators of the therapeutic features of MSC, this platform also was evaluated for EV production. Upon a 24-h period of conditioning, secreted EVs were isolated by ultrafiltration followed by anion-exchange chromatography and exhibited the typical cup-shaped morphology, small size distribution (162.6 ± 30.2 nm) and expressed EV markers (CD63, CD9 and syntenin-1). CONCLUSIONS: Taken together, we established a time-effective and robust scalable platform that complies with clinical-grade standards for the dual production of MSC(WJ) and their derived EV.

3.
EJNMMI Res ; 14(1): 26, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38453813

ABSTRACT

BACKGROUND: Glioblastoma is an extremely aggressive malignant tumor with a very poor prognosis. Due to the increased proliferation rate of glioblastoma, there is the development of hypoxic regions, characterized by an increased concentration of copper (Cu). Considering this, 64Cu has attracted attention as a possible theranostic radionuclide for glioblastoma. In particular, [64Cu]CuCl2 accumulates in glioblastoma, being considered a suitable agent for positron emission tomography. Here, we explore further the theranostic potential of [64Cu]CuCl2, by studying its therapeutic effects in advanced three-dimensional glioblastoma cellular models. First, we established spheroids from three glioblastoma (T98G, U373, and U87) and a non-tumoral astrocytic cell line. Then, we evaluated the therapeutic responses of spheroids to [64Cu]CuCl2 exposure by analyzing spheroids' growth, viability, and cells' proliferative capacity. Afterward, we studied possible mechanisms responsible for the therapeutic outcomes, including the uptake of 64Cu, the expression levels of a copper transporter (CTR1), the presence of a cancer stem cell population, and the production of reactive oxygen species (ROS). RESULTS: Results revealed that [64Cu]CuCl2 is able to significantly reduce spheroids' growth and viability, while also affecting cells' proliferation capacity. The uptake of 64Cu, the presence of cancer stem-like cells and the production of ROS were in accordance with the therapeutic response. However, expression levels of CTR1 were not in agreement with uptake levels, revealing that other mechanisms could be involved in the uptake of 64Cu. CONCLUSIONS: Overall, our results further support [64Cu]CuCl2 potential as a theranostic agent for glioblastoma, unveiling potential mechanisms that could be involved in the therapeutic response.

4.
Cytotherapy ; 2024 Feb 18.
Article in English | MEDLINE | ID: mdl-38483360

ABSTRACT

BACKGROUND AIMS: Parkinson's disease (PD) is the second most common neurodegenerative disorder. The etiology of the disease remains largely unknown, but evidence have suggested that the overexpression and aggregation of alpha-synuclein (α-syn) play key roles in the pathogenesis and progression of PD. Mesenchymal stromal cells (MSCs) have been earning attention in this field, mainly due to their paracrine capacity. The bioactive molecules secreted by MSCs, i.e. their secretome, have been associated with enhanced neuronal survival as well as a strong modulatory capacity of the microenvironments where the disease develops. The selection of the appropriate animal model is crucial in studies of efficacy assessment. Given the involvement of α-syn in the pathogenesis of PD, the evidence generated from the use of animal models that develop a pathologic phenotype due to the action of this protein is extremely valuable. Therefore, in this work, we established an animal model based on the viral vector-mediated overexpression of A53T α-syn and studied the impact of the secretome of bone marrow mesenchymal stromal cells MSC(M) as a therapeutic strategy. METHODS: Adult male rats were subjected to α-syn over expression in the nigrostriatal pathway to model dopaminergic neurodegeneration. The impact of locally administered secretome treatment from MSC(M) was studied. Motor impairments were assessed throughout the study coupled with whole-region (striatum and substantia nigra) confocal microscopy evaluation of histopathological changes associated with dopaminergic neurodegeneration and glial cell reactivity. RESULTS: Ten weeks after lesion induction, the animals received secretome injections in the substantia nigra pars compacta (SNpc) and striatum (STR). The secretome used was produced from bone marrow mesenchymal stromal cells MSC(M) expanded in a spinner flask (SP) system. Nine weeks later, animals that received the viral vector containing the gene for A53T α-syn and treated with vehicle (Neurobasal-A medium) presented dopaminergic cell loss in the SNpc and denervation in the STR. The treatment with secretome significantly reduced the levels of α-syn in the SNpc and protected the dopaminergic neurons (DAn) within the SNpc and STR. CONCLUSIONS: Our results are aligned with previous studies in both α-syn Caenorhabditis elegans models, as well as 6-OHDA rodent model, revealing that secretome exerted a neuroprotective effect. Moreover, these effects were associated with a modulation of microglial reactivity supporting an immunomodulatory role for the factors contained within the secretome. This further supports the development of new studies exploring the effects and the mechanism of action of secretome from MSC(M) against α-syn-induced neurotoxicity.

5.
Clinics (Sao Paulo) ; 79: 100328, 2024.
Article in English | MEDLINE | ID: mdl-38412639

ABSTRACT

OBJECTIVE: To adapt the Scale of Perception of Respect for and Maintenance of the Dignity of the Inpatient (CuPDPH) to the Brazilian language and culture and to assess its psychometric properties. RESULTS: The scale was evaluated by 15 experts, and 239 patients from three tertiary hospitals in Rio de Janeiro. All participants signed a consent form. Data have shown adequacy of the model (KMO=0.839, Bartlett's test of sphericity: χ2(171) = 2241.3, p = 0.000010), good adjusted content validity (CVCa ≥ 0.90), internal consistency and reliability, such as α = 0.927. DISCUSSION: CuPDPH is a rating scale on observable professional attitudes. Illnesses change lives and impose adaptation to a new situation, perceived as depersonalization, leading patients to try to regain control of their lives. Patients expressed "ill will" to fill out the scale. Psychiatric patients' scale filling time was higher than others. A sample from three Rio de Janeiro third-level hospitals may not reflect the country's population; also, this adaptation may not comprise all linguistic variations of Brazilian Portuguese and Portuguese-speaking countries. CONCLUSION: The Portuguese version of the Scale of Perception of Respect for and Maintenance of the Dignity of the Inpatient (CuPDPH), a 19-item, six-component version is a reliable instrument to measure the perception of internal medicine, surgical, and psychiatric patients on the maintenance of their dignity in Rio de Janeiro, Brazil. This knowledge could be used in advancing research on patients' perception of dignity, as well as professional ethical competencies, staff-patient relationship skills, and leadership development in medical and other healthcare professional education.


Subject(s)
Cross-Cultural Comparison , Inpatients , Humans , Brazil , Cross-Sectional Studies , Surveys and Questionnaires , Psychometrics , Respect , Reproducibility of Results , Language , Perception , Translations
6.
Forensic Sci Int Genet ; 69: 102999, 2024 03.
Article in English | MEDLINE | ID: mdl-38181588

ABSTRACT

The Spanish and Portuguese Speaking Working Group of the International Society for Forensic Genetics (GHEP-ISFG) organized a collaborative study on mutations of Y-chromosomal short tandem repeats (Y-STRs). New data from 2225 father-son duos and data from 44 previously published reports, corresponding to 25,729 duos, were collected and analyzed. Marker-specific mutation rates were estimated for 33 Y-STRs. Although highly dependent on the analyzed marker, mutations compatible with the gain or loss of a single repeat were 23.2 times more likely than those involving a greater number of repeats. Longer alleles (relatively to the modal one) showed to be nearly twice more mutable than the shorter ones. Within the subset of longer alleles, the loss of repeats showed to be nearly twice more likely than the gain. Conversely, shorter alleles showed a symmetrical trend, with repeat gains being twofold more frequent than reductions. A positive correlation between the paternal age and the mutation rate was observed, strengthening previous findings. The results of a machine learning approach, via logistic regression analyses, allowed the establishment of algebraic formulas for estimating the probability of mutation depending on paternal age and allele length for DYS389I, DYS393 and DYS627. Algebraic formulas could also be established considering only the allele length as predictor for DYS19, DYS389I, DYS389II-I, DYS390, DYS391, DYS393, DYS437, DYS439, DYS449, DYS456, DYS458, DYS460, DYS481, DYS518, DYS533, DYS576, DYS626 and DYS627 loci. For the remaining Y-STRs, a lack of statistical significance was observed, probably as a consequence of the small effective size of the subsets available, a common difficulty in the modeling of rare events as is the case of mutations. The amount of data used in the different analyses varied widely, depending on how the data were reported in the publications analyzed. This shows a regrettable waste of produced data, due to inadequate communication of the results, supporting an urgent need of publication guidelines for mutation studies.


Subject(s)
Chromosomes, Human, Y , DNA Fingerprinting , Humans , Microsatellite Repeats , Ethnicity/genetics , Mutation , Haplotypes , Genetics, Population
7.
J Environ Manage ; 352: 120031, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38232587

ABSTRACT

Bees are primary pollinators across various terrestrial biomes and rely heavily on floral resources for sustenance. The composition of landscapes can influence bee foraging behavior, while human activities can directly affect both the composition and nutritional value of bee food. We aimed to assess how landscape structure and land use practices can impact the composition and nutritional value of food sources for two generalist social bee species, Apis mellifera and Scaptotrigona postica. Food samples were collected from twenty-five colonies of A. mellifera and thirteen of S. postica to examine how food composition and nutritional value may vary based on the extent of human land use and the composition of landscapes surrounding beekeeping sites. The pollen composition and nutritional value of A. mellifera were influenced by both land use practices and landscape heterogeneity. The number of patches determined total sugar and lipid content. Landscape heterogeneity affected pollen composition in S. postica, primarily due to the number of patches, while total sugar was affected by landscape diversity. Pollen nutritional value in S. postica was linked to land use, mainly meadow and vegetation, which influenced total sugar and dry matter. S. postica showed a higher sensitivity to land use changes compared to A. mellifera, which was more affected by landscape heterogeneity. Assuring landscape heterogeneity by preserving remaining forest patches around apiaries and meliponaries is crucial. Thoughtful land use planning is essential to support beekeeping activities and ensure an adequate quantity and quality of bee food resources.


Subject(s)
Ecosystem , Pollen , Humans , Bees , Animals , Pollen/chemistry , Food , Forests , Sugars/analysis
8.
Int J Nurs Knowl ; 35(2): 186-194, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37300360

ABSTRACT

PURPOSE: To evaluate the accuracy of defining characteristics and causal relationships of the etiological factors of the nursing diagnosis deficient knowledge in individuals with heart failure . DATA SOURCES: An analytical, cross-sectional study on the diagnostic accuracy of the defining characteristics and causal relationships of the etiological factors of the nursing diagnosis. The sample consisted of 140 patients with chronic HF and in outpatient follow-up. The latent class analysis method was used to test the accuracy of measurements and estimate the prevalence of the diagnosis. The calculation of subsequent probabilities and the odds ratio ( were also parameters employed. The study was approved by the Research Ethics Committee of the Federal University of Pernambuco. DATA SYNTHESIS: The diagnosis had an estimated prevalence of 38.57% in the sample. The inaccurate statements about the disease and/or therapy, self-care deficient performance, and inadequate behavior were the clinical indicators that best predicted the presence of the diagnosis and demonstrated the same sensitivity value (1.0000), specificity (1.0000), and 95% confidence interval (0.9999-1.0000) for all. The populations at risk was elderly (OR = 2.12, confidence interval 95% = 1.05-4.27), and illiterate individuals (OR = 2.07, confidence interval 95% = 1.03-4.16) had an approximately twofold great chance of developing havening deficient knowledge. CONCLUSION: The evaluation of the accuracy of clinical indicators, corresponding to the defining characteristics in the study, contributed to screening and diagnostic establishment capacity in clinical practice, and to the translation of theoretical and practical knowledge. IMPLICATIONS FOR NURSING PRACTICE: Accurate clinical indicators of the nursing diagnosis deficient knowledge facilitate the clinical reasoning of nurses and favor the professional's role in the development of health education strategies focused on the acquisition of knowledge about the disease by patients, family members, and caregivers.


OBJETIVO: Avaliar a acurácia das características definidoras e relações causais dos fatores etiológicos do diagnóstico de enfermagem Conhecimento deficiente em pacientes com insuficiência cardíaca. FONTE DE DADOS: Estudo analítico, transversal, sobre a acurácia diagnóstica das características definidoras e relações causais dos fatores etiológicos do diagnóstico de enfermagem. A amostra foi composta por 140 pacientes com insuficiência cardíaca crônica e em acompanhamento ambulatorial. O método de análise de classes latentes foi utilizado para testar as medidas de acurácia e estimar a prevalência do diagnóstico. O cálculo de probabilidades posteriores e a Odds Ratio também foram parâmetros empregados. O estudo teve aprovação do Comitê de Ética em Pesquisa da Universidade Federal de Pernambuco. SÍNTESE DE DADOS: O diagnóstico apresentou prevalência estimada de 38,57% na população. As Declarações imprecisas sobre a doença e/ou terapêutica, Déficit no desempenho do autocuidado e Comportamento inadequado foram os indicadores clínicos que melhor predisseram a presença do diagnóstico e demonstraram o mesmo valor de sensibilidade (1.0000), especificidade (1.0000) e intervalo de confiança 95% (0.9999­1.0000) para todos. As populações em risco Idoso (Odds Ratio = 2.12, intervalo de confiança 95% = 1.05­4.27) e Indivíduos analfabetos (Odds Ratio = 2.07, intervalo de confiança 95% = 1.03­4.16) apresentaram, aproximadamente, duas vezes a chance de desenvolver o conhecimento deficiente. CONCLUSÃO: A avaliação da acurácia dos indicadores clínicos, correspondentes as características definidoras no estudo, contribuiu para a capacidade de triagem e estabelecimento de diagnósticos na prática clínica e para a tradução de conhecimentos teóricos e práticos. IMPLICAÇÕES PARA PRÁTICA DE ENFERMAGEM: Indicadores clínicos acurados do diagnóstico de enfermagem Conhecimento deficiente facilitam o raciocínio clínico do enfermeiro e favorecem a atuação do profissional na elaboração de estratégias de educação em saúde focadas na aquisição do conhecimento sobre a doença por parte de pacientes, familiares e cuidadores.


Subject(s)
Heart Failure , Humans , Aged , Cross-Sectional Studies , Family , Nursing Diagnosis , Outpatients
9.
Org Biomol Chem ; 21(46): 9242-9254, 2023 11 29.
Article in English | MEDLINE | ID: mdl-37966045

ABSTRACT

This study presents the synthesis of novel glycoconjugates by connecting benzazole and carbohydrate units with a 1,2,3-triazole linker. A simple synthetic route employing a copper(I) catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) was utilized. The synthesized compounds exhibit excited-state intramolecular proton transfer (ESIPT), resulting in longer wavelength emission with a significantly large Stokes shift (∼10 000 cm-1). These compounds show potential as chemical sensors due to their ability to detect Cu2+ ions, causing a decrease in fluorescence emission (turn-off effect). Additionally, they demonstrate strong interaction with proteins, exemplified by their interaction with bovine serum albumin (BSA) as a model protein.


Subject(s)
Copper , Serum Albumin, Bovine , Serum Albumin, Bovine/chemistry , Copper/chemistry , Glycoconjugates , Triazoles
10.
Tissue Eng Part C Methods ; 29(12): 583-595, 2023 12.
Article in English | MEDLINE | ID: mdl-37842845

ABSTRACT

Fecal incontinence, although not life-threatening, has a high impact on the economy and patient quality of life. So far, available treatments are based on both surgical and nonsurgical approaches. These can range from changes in diet, to bowel training, or sacral nerve stimulation, but none of which provides a long-term solution. New regenerative medicine-based therapies are emerging, which aim at regenerating the sphincter muscle and restoring continence. Usually, these consist of the administration of a suspension of expanded skeletal-derived muscle cells (SkMDCs) to the damaged site. However, this strategy often results in a reduced cell viability due to the need for cell harvesting from the expansion platform, as well as the non-native use of a cell suspension to deliver the anchorage-dependent cells. In this study, we propose the proof-of-concept for the bioprocessing of a new cell delivery method for the treatment of fecal incontinence, obtained by a scalable two-step process. First, patient-isolated SkMDCs were expanded using planar static culture systems. Second, by using a single-use PBS-MINI Vertical-Wheel® bioreactor, the expanded SkMDCs were combined with biocompatible and biodegradable (i.e., directly implantable) poly(lactic-co-glycolic acid) microcarriers prepared by thermally induced phase separation. This process allowed for up to 80% efficiency of SkMDCs to attach to the microcarriers. Importantly, SkMDCs were viable during all the process and maintained their myogenic features (e.g., expression of the CD56 marker) after adhesion and culture on the microcarriers. When SkMDC-containing microcarriers were placed on a culture dish, cells were able to migrate from the microcarriers onto the culture surface and differentiate into multinucleated myotubes, which highlights their potential to regenerate the damaged sphincter muscle after administration into the patient. Overall, this study proposes an innovative method to attach SkMDCs to biodegradable microcarriers, which can provide a new treatment for fecal incontinence.


Subject(s)
Cell Culture Techniques , Fecal Incontinence , Humans , Cell Culture Techniques/methods , Quality of Life , Bioreactors , Muscles
11.
Bioengineering (Basel) ; 10(9)2023 Sep 09.
Article in English | MEDLINE | ID: mdl-37760170

ABSTRACT

Tissue engineering approaches within the muscle context represent a promising emerging field to address the current therapeutic challenges related with multiple pathological conditions affecting the muscle compartments, either skeletal muscle or smooth muscle, responsible for involuntary and voluntary contraction, respectively. In this review, several features and parameters involved in the bioprocessing of muscle cells are addressed. The cell isolation process is depicted, depending on the type of tissue (smooth or skeletal muscle), followed by the description of the challenges involving the use of adult donor tissue and the strategies to overcome the hurdles of reaching relevant cell numbers towards a clinical application. Specifically, the use of stem/progenitor cells is highlighted as a source for smooth and skeletal muscle cells towards the development of a cellular product able to maintain the target cell's identity and functionality. Moreover, taking into account the need for a robust and cost-effective bioprocess for cell manufacturing, the combination of muscle cells with biomaterials and the need for scale-up envisioning clinical applications are also approached.

12.
Arch Oral Biol ; 155: 105799, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37672969

ABSTRACT

OBJECTIVE: Assess risk factors, local and systemic immunological biomarkers in healthy individuals and with Denture Stomatitis (DS). DESIGN: For this observational transversal study, 27 participants without DS (Group 0), 24 with moderate DS (Group 1), and 25 with severe DS (Group 2) were assessed for sociodemographic, behavioral, and clinical parameters, microbial load of Candida spp., Staphylococcus spp., Streptococcus mutans, Pseudomonas spp., and enterobacteria, and cytokine and C-reactive protein levels. ANOVA, Fisher's exact, Kruskal-Wallis, Mann-Whitney, Wilcoxon and Pearson's chi-square tests were used for data analysis (α = 0.05). RESULTS: Group 1 had a significantly higher mean age compared to the other groups (P = 0.018), but no correlation was identified between age and DS (P = 0.830; r = 0.025). No significant differences were found among the groups for other sociodemographic and behavioral characteristics. Group 1 had significantly older upper and lower dentures; however, no correlation was identified between age of upper (P = 0.522; r = 0.075) and lower (P = 0.143; r = 0.195) dentures and DS. The microbial load of Candida albicans on the dentures (P = 0.035) and Candida spp. on the palate (P = 0.008) of the groups 1 and 2 was higher than group 0. Group 1 and 2 had higher Candida spp. counts on denture (P = 0.003) than group 0. There was no difference among groups for bacterial analyzed. Group 1 showed higher and Group 2 intermediate salivary levels of IL-6 compared to Group 0. There was no difference in the C-reactive protein levels among groups. CONCLUSIONS: Microbial load of Candida spp. is the factor with the strongest relationship with DS, with capacity for local signaling through IL-6.

13.
Parasitol Res ; 122(10): 2367-2377, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37587388

ABSTRACT

Human contact with wild animals in synanthropic habits is often mediated by arthropod vectors such as ticks. This is an important method of spreading infectious agents that pose a risk to human health. Thus, this study aimed to molecularly detect Ehrlichia spp., Anaplasma spp., Borrelia spp., and protozoa of the order Piroplasmida in ticks collected from coatis of Iguaçu National Park (PNI), Paraná, Brazil. This study involved 553 ticks DNA, including Amblyomma spp. larvae, Haemaphysalis juxtakochi nymphs, Amblyomma brasiliense, Amblyomma coelebs, and adults of Amblyomma ovale. The DNA extracted from each sample was subjected to polymerase chain reaction (PCR) targeting the genes 23S rRNA for the Anaplasmataceae family, 16S rRNA for Anaplasma spp., dsb for Ehrlichia spp., flaB, 16S rRNA, hpt, and glpQ for Borrelia spp., and 18S rRNA for Piroplasmid protozoans. DNA from Anaplasma sp. was detected in ticks of the species A. coelebs (4/553); Borrelia sp. DNA was detected in A. coelebs (3/553), A. ovale (1/553), and Amblyomma larvae (1/553); and Theileria sp. was detected in A. coelebs (2/553). All tested samples were negative for Ehrlichia spp. Our study constitutes the newest report in South America of these microorganisms, which remain poorly studied.


Subject(s)
Borrelia , Procyonidae , Ticks , Adult , Animals , Humans , RNA, Ribosomal, 16S/genetics , Brazil , Parks, Recreational , Ecosystem , Forests , Amblyomma , Anaplasma/genetics , Borrelia/genetics , Ehrlichia/genetics , Larva
14.
Biotechnol Bioeng ; 120(9): 2742-2755, 2023 09.
Article in English | MEDLINE | ID: mdl-37318000

ABSTRACT

The therapeutic effects of human mesenchymal stromal cells (MSC) have been attributed mostly to their paracrine activity, exerted through small-secreted extracellular vesicles (EVs) rather than their engraftment into injured tissues. Currently, the production of MSC-derived EVs (MSC-EVs) is performed in laborious static culture systems with limited manufacturing capacity using serum-containing media. In this work, a serum-/xenogeneic-free microcarrier-based culture system was successfully established for bone marrow-derived MSC cultivation and MSC-EV production using a 2  l-scale controlled stirred tank reactor (STR) operated under fed-batch (FB) or fed-batch combined with continuous perfusion (FB/CP). Overall, maximal cell numbers of (3.0 ± 0.12) × 108 and (5.3 ± 0.32) × 108 were attained at Days 8 and 12 for FB and FB/CP cultures, respectively, and MSC(M) expanded under both conditions retained their immunophenotype. MSC-EVs were identified in the conditioned medium collected from all STR cultures by transmission electron microscopy, and EV protein markers were successfully identified by Western blot analysis. Overall, no significant differences were observed between EVs isolated from MSC expanded in STR operated under the two feeding approaches. EV mean sizes of 163 ± 5.27 nm and 162 ± 4.44 nm (p > 0.05) and concentrations of (2.4 ± 0.35) × 1011 EVs/mL and (3.0 ± 0.48) × 1011 EVs/mL (p > 0.05) were estimated by nanoparticle tracking analysis for FB and FB/CP cultures, respectively. The STR-based platform optimized herein represents a major contribution toward the development of human MSC- and MSC-EV-based products as promising therapeutic agents for Regenerative Medicine settings.


Subject(s)
Extracellular Vesicles , Mesenchymal Stem Cells , Humans , Batch Cell Culture Techniques , Extracellular Vesicles/metabolism , Regenerative Medicine , Cell Proliferation
15.
Syst Rev ; 12(1): 79, 2023 05 05.
Article in English | MEDLINE | ID: mdl-37147732

ABSTRACT

BACKGROUND: Medical schools have used mindfulness meditation as a strategy to assist students in stress management. This study aimed to seek evidence regarding the effectiveness of mindfulness-based training programs in reducing psychological distress and promoting the well-being of medical students. METHODS: We conducted a systematic review and meta-analysis. Cochrane Library, Embase, PubMed/MEDLINE, PsycINFO/PsycNet, LILACS/BVS, ERIC (ProQuest), Web of Science, OpenGrey, and Google Scholar were searched for randomized clinical trials published until March 2022, without time or language restrictions. Two authors independently screened the articles, extracted data using a standardized extraction form, and assessed the methodological quality of the included studies using the Cochrane's Risk of Bias 2 (ROB 2) tool and the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. RESULTS: Of the 848 articles retrieved, 8 met the inclusion criteria. Mindfulness-based training improved the outcomes: mindfulness (small post-intervention effect: SMD = 0.29; 95% CI: 0.03 to 0.54; p = 0.03; I2 = 46%; high evidence quality, and small effect at follow-up: SMD = 0.37; 95% CI: 0.04 to 0.70; p = 0.03; I2 = 53%; low evidence quality), psychological well-being/health (there was no statistically significant difference between the groups in the post-intervention effect: SMD = - 0.27; 95% CI: - 0.67 to 0.13; p = 0.18; I2 = 76%; moderate evidence quality, and a significant difference at follow-up: SMD = - 0.73; 95% CI: - 1.23 to - 0.23; p = 0.004; I2 = 61%; low evidence quality), and stress (small post-intervention effect: SMD = - 0.29; CI of 95%: - 0.56 to - 0.02; p = 0.04; I2 = 57%; moderate evidence quality, and moderate effect at follow-up: SMD = - 0.45, 95% CI: - 0.67 to - 0.22, p = 0.0001, I2 = 0%, moderate evidence quality). The quality of evidence for the anxiety, depression, and resilience outcomes is low and for the empathy outcome, very low. CONCLUSION: The results indicate that the students who participated in the mindfulness training perceived improvements in the stress and psychological distress symptoms and improved health perception and psychological well-being. However, the significant heterogeneity among studies should be considered when interpreting these findings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020153169.


Subject(s)
Mindfulness , Students, Medical , Humans , Mindfulness/methods , Stress, Psychological/prevention & control , Depression , Anxiety
16.
Biomedicines ; 11(4)2023 Apr 21.
Article in English | MEDLINE | ID: mdl-37189850

ABSTRACT

Extracellular vesicles (EVs) are cell-derived nano-sized lipid membranous structures that modulate cell-cell communication by transporting a variety of biologically active cellular components. The potential of EVs in delivering functional cargos to targeted cells, their capacity to cross biological barriers, as well as their high modification flexibility, make them promising drug delivery vehicles for cell-free therapies. Mesenchymal stromal cells (MSCs) are known for their great paracrine trophic activity, which is largely sustained by the secretion of EVs. MSC-derived EVs (MSC-EVs) retain important features of the parental cells and can be bioengineered to improve their therapeutic payload and target specificity, demonstrating increased therapeutic potential in numerous pre-clinical animal models, including in the treatment of cancer and several degenerative diseases. Here, we review the fundamentals of EV biology and the bioengineering strategies currently available to maximize the therapeutic value of EVs, focusing on their cargo and surface manipulation. Then, a comprehensive overview of the methods and applications of bioengineered MSC-EVs is presented, while discussing the technical hurdles yet to be addressed before their clinical translation as therapeutic agents.

17.
Biomedicines ; 11(5)2023 Apr 22.
Article in English | MEDLINE | ID: mdl-37238911

ABSTRACT

Parkinson's disease (PD) is the second most common neurodegenerative disorder and is characterized by the degeneration of the dopamine (DA) neurons in the substantia nigra pars compacta, leading to a loss of DA in the basal ganglia. The presence of aggregates of alpha-synuclein (α-synuclein) is seen as the main contributor to the pathogenesis and progression of PD. Evidence suggests that the secretome of mesenchymal stromal cells (MSC) could be a potential cell-free therapy for PD. However, to accelerate the integration of this therapy in the clinical setting, there is still the need to develop a protocol for the large-scale production of secretome under good manufacturing practices (GMP) guidelines. Bioreactors have the capacity to produce large quantities of secretomes in a scalable manner, surpassing the limitations of planar static culture systems. However, few studies focused on the influence of the culture system used to expand MSC, on the secretome composition. In this work, we studied the capacity of the secretome produced by bone marrow-derived mesenchymal stromal cells (BMSC) expanded in a spinner flask (SP) and in a Vertical-Wheel™ bioreactor (VWBR) system, to induce neurodifferentiation of human neural progenitor cells (hNPCs) and to prevent dopaminergic neuron degeneration caused by the overexpression of α-synuclein in one Caenorhabditis elegans model of PD. Results showed that secretomes from both systems were able to induce neurodifferentiation, though the secretome produced in the SP system had a greater effect. Additionally, in the conditions of our study, only the secretome produced in SP had a neuroprotective potential. Lastly, the secretomes had different profiles regarding the presence and/or specific intensity of different molecules, namely, interleukin (IL)-6, IL-4, matrix metalloproteinase-2 (MMP2), and 3 (MMP3), tumor necrosis factor-beta (TNF-ß), osteopontin, nerve growth factor beta (NGFß), granulocyte colony-stimulating factor (GCSF), heparin-binding (HB) epithelial growth factor (EGF)-like growth factor (HB-EGF), and IL-13. Overall, our results suggest that the culture conditions might have influenced the secretory profiles of cultured cells and, consequently, the observed effects. Additional studies should further explore the effects that different culture systems have on the secretome potential of PD.

18.
Biomedicines ; 11(5)2023 May 03.
Article in English | MEDLINE | ID: mdl-37239023

ABSTRACT

Cell-based therapies using periodontal ligament stromal cells (PDLSC) for periodontal regeneration may represent an alternative source for mesenchymal stromal cells (MSC) to MSC derived from bone marrow (MSC(M)) and adipose tissue (MSC(AT)). We aimed to characterize the osteogenic/periodontal potential of PDLSC in comparison to MSC(M) and MSC(AT). PDLSC were obtained from surgically extracted healthy human third molars, while MSC(M) and MSC(AT) were obtained from a previously established cell bank. Flow cytometry, immunocytochemistry, and cell proliferation analyses provided cellular characteristics from each group. Cells from the three groups presented MSC-like morphology, MSC-related marker expression, and multilineage differentiation capacity (adipogenic, chondrogenic, and osteogenic). In this study, PDLSC expressed osteopontin, osteocalcin, and asporin, while MSC(M) and MSC(AT) did not. Of note, only PDLSC expressed CD146, a marker previously applied to identify PDLSC, and presented higher proliferative potential compared to MSC(M) and MSC(AT). Upon osteogenic induction, PDLSC exhibited higher calcium content and enhanced upregulation of osteogenic/periodontal genes compared to MSC(M) and MSC(AT), such as Runx2, Col1A1 and CEMP-1. However, the alkaline phosphatase activity of PDLSC did not increase. Our findings suggest that PDLSC might be a promising cell source for periodontal regeneration, presenting enhanced proliferative and osteogenic potential compared to MSC(M) and MSC(AT).

19.
Article in Portuguese | LILACS-Express | LILACS, BDENF - Nursing | ID: biblio-1537073

ABSTRACT

Introdujo: a educagáo em saúde de adolescentes com foco na sexualidade é favorecida pelo emprego de tecnologias cuidativo- educacionais. Objetivo: construir e validar uma tecnologia educacional, do tipo jogo de tabuleiro, para mediar a discussáo de tópicos referentes a sexualidade com a populado adolescente. Materiais e métodos: estudo metodológico delineado em tres etapas, a saber: 1°) delimitado do conteúdo a ser abordado, 2°) elaborado do protótipo do jogo, 3°) validado do conteúdo e aparencia por juízes especialistas. Resultados e discussao: "Match" é um jogo de tabuleiro, com perguntas temáticas relacionados a sexualidade que direcionam o jogador do início ao fim do trajeto. Deu-se enfase a incorporado de elementos da gamificagáo, tais como, sorte, estratégia, competido e cooperado. O processo de validado obteve éxito em todas as categorias avaliadas, o jogo foi considerado relevante e adequado as atividades de educado em saúde. Conclusdes: O jogo elaborado encontra-se validado e disponível a comunidade científica e profissional, e deverá ter os seus efeitos mensurados nas próximas etapas da pesquisa. Além disso, uma versáo digital da ferramenta deve ser construída para elevar o seu alcance.


Introduction: health education for adolescents with a focus on sexuality is favored using care- educational technologies. Objective: to build and validate an educational technology, like a board game, to mediate the discussion of topics related to sexuality with the adolescent population. Materials and methods: methodological study outlined in three stages, namely: 1st) delimitation of the content to be addressed, 2nd) creation of the game prototype, 3rd) validation of the content and appearance by expert judges. Results and discussion: "Match" is a board game, with thematic questions related to sexuality that direct the player from the beginning to the end of the path. Emphasis was placed on the incorporation of gamification elements, such as luck, strategy, competition, and cooperation. The validation process was successful in all evaluated categories, the game was considered relevant and suitable for health education activities. Conclusions: The developed game is validated and available to the scientific and professional community, and its effects should be measured in the next stages of the research. In addition, a digital version of the tool must be built to increase its reach.


Introducción: la educación en salud de los adolescentes con enfoque en la sexualidad se ve favorecida por el uso de tecnologías cuidado - educativas. Objetivo: construir y validar una tecnología educativa, a modo de juego de mesa, para mediar en la discusión de temas relacionados a la sexualidad con la población adolescente. Materiales y métodos: estudio metodológico planteado en tres etapas, a saber: 1a) delimitación del contenido a abordar, 2a) creación del prototipo del juego, 3a) validación del contenido y apariencia por jueces expertos. Resultados y discusión: "Match" es un juego de mesa, con preguntas temáticas relacionadas con la sexualidad que dirigen al jugador desde el principio hasta el final del viaje. Se hizo hincapié en la incorporación de elementos de gamificación, como la suerte, la estrategia, la competencia y la cooperación. El proceso de validación fue exitoso en todas las categorías evaluadas, el juego fue considerado relevante y adecuado para actividades de educación en salud. Conclusiones: el juego desarrollado está validado y disponible para la comunidad científica y profesional, y sus efectos deben medirse en las próximas etapas de la investigación. Además, se debe construir una versión digital de la herramienta para aumentar su alcance.

20.
Int J Nurs Knowl ; 34(2): 116-125, 2023 Apr.
Article in English | MEDLINE | ID: mdl-35794806

ABSTRACT

OBJECTIVE: To analyze the content of the nursing diagnosis deficient knowledge in individuals with heart failure. METHODS: Methodological study to validate the content of a nursing diagnosis based on the predictive model of diversity, carried out through the organization of the phenomenon of interest and analysis by judges using the collective wisdom model. The NANDA-I Knowledge Deficient diagnosis was evaluated by 48 judges and considered valid when it presented a median content validity index ≥ 0.8 in the confidence intervals. RESULTS: Note that 66.6% of the judges indicated that the new definition proposed was more adequate than the definition adopted by NANDA-I. After the experts' analysis, the following defining characteristics were considered valid: inaccurate statements about the disease and/or therapy, inadequate performance in the management of intercurrences, increase in hospital readmissions, worsened quality of life, deficit in self-care performance, and follow-up of inadequate instruction; related factors are as follows: inadequate guidance offered by health professionals, nonparticipation of the patient in the planning of their health care, weakened relationship between professional and individual; populations at risk-elderly and low level of education of the individual and/or caregiver and the associated condition, mild cognitive impairment. Anxiety, depression, and impaired social interaction were elements considered not relevant to the content domain. CONCLUSION: The validation of the content of the aforementioned diagnosis in patients with heart failure, through the analysis of judges with different degrees of expertise, made it possible to improve the definition and expansion of new diagnostic indicators. IMPLICATIONS FOR NURSING PRACTICE: Updated diagnostic elements for the nursing diagnosis deficient knowledge in individuals with heart failure will facilitate accurate clinical judgment and the establishment of a therapeutic plan aimed at etiological factors modifiable by nurses.


Subject(s)
Heart Failure , Nursing Diagnosis , Humans , Aged , Quality of Life , Anxiety/diagnosis , Risk Factors , Heart Failure/diagnosis
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