RESUMEN
BACKGROUND: Pitaya fruit (Hylocereus spp.) is rich in bioactive compounds such as betanin. This study aimed to extract betanin-rich pitaya fruit and encapsulate it in electrospun nanofibers produced with sweet potato starch. The influence of different concentrations of this bioactive compound on the morphology, functional groups, hydrophilicity, load capacity, color, thermal properties, and contact angle of the electrospun nanofibers with water and milk was assessed. The potential antioxidant and stability of nanofibers during gastrointestinal digestion in vitro were demonstrated. RESULTS: The nanofibers presented average diameters ranging from 134 to 204 nm and displayed homogeneous morphology. The load capacity of the extract in the nanofibers was 43% to 83%. The encapsulation increased the thermal resistance of betanins (197-297 °C). The static contact angle with water and milk showed that these materials presented greater affinity with milk. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) showed that the nanofibers with 5%, 25%, and 45% pitaya extract presented unique characteristics. They showed resistance in delivering betanins to the stomach, with 12% inhibition of the 2,2-diphenyl-1-picrylhydrazyl (DPPHË) radical. However, only the 45% concentration reached the intestine with 9.83% inhibition of the DPPHË radical. CONCLUSIONS: Pattern recognition from multivariate analyses indicated that nanofibers containing 5%, 25%, and 45% of the extract presented distinct characteristics, with the ability to preserve betanins against thermal degradation and perform the controlled delivery of these bioactives in the stomach and intestine to produce antioxidant activity. © 2024 Society of Chemical Industry.
RESUMEN
This study assessed the safety and efficacy of OncoTherad® (MRB-CFI-1) nanoimmunotherapy for non-muscle invasive bladder cancer (NMIBC) patients unresponsive to Bacillus Calmette-Guérin (BCG) and explored its mechanisms of action in a bladder cancer microenvironment. A single-arm phase I/II study was conducted with 44 patients with NMIBC who were unresponsive to BCG treatment. Primary outcomes were pathological complete response (pCR) and relapse-free survival (RFS). Secondary outcomes comprised response duration and therapy safety. Patients' mean age was 65 years; 59.1% of them were refractory, 31.8% relapsed, and 9.1% were intolerant to BCG. Moreover, the pCR rate after 24 months reached 72.7% (95% CI), whereas the mean RFS reached 21.4 months. Mean response duration in the pCR group was 14.3 months. No patient developed muscle-invasive or metastatic disease during treatment. Treatment-related adverse events occurred in 77.3% of patients, mostly grade 1-2 events. OncoTherad® activated the innate immune system through toll-like receptor 4, leading to increased interferon signaling. This activation played a crucial role in activating CX3CR1+ CD8 T cells, decreasing immune checkpoint molecules, and reversing immunosuppression in the bladder microenvironment. OncoTherad® has proved to be a safe and effective therapeutic option for patients with BCG-unresponsive NMIBC, besides showing likely advantages in tumor relapse prevention processes.
Asunto(s)
Inmunoterapia , Neoplasias Vesicales sin Invasión Muscular , Neoplasias de la Vejiga Urinaria , Anciano , Humanos , Adyuvantes Inmunológicos/uso terapéutico , Administración Intravesical , Vacuna BCG/uso terapéutico , Receptor 1 de Quimiocinas CX3C , Invasividad Neoplásica , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Vesicales sin Invasión Muscular/terapia , Transducción de Señal , Receptor Toll-Like 4/uso terapéutico , Microambiente Tumoral , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Inmunoterapia/métodos , Sistema de Administración de Fármacos con NanopartículasRESUMEN
Toxoplasma gondii, a protozoan parasite, is responsible for toxoplasmosis. The available therapy for patients with toxoplasmosis involves a combination of pyrimethamine and sulfadiazine, which have several adverse effects, including bone marrow suppression, megaloblastic anemia, leukopenia, and granulocytopenia. The development of therapeutic alternatives is essential for the management of toxoplasmosis, emphasizing the recent advances in nanomedicine. This study aimed to evaluate the in vitro effects of biogenic silver nanoparticles (AgNp-Bio) on tachyzoite forms and Leydig cells infected with T. gondii. We observed that the AgNp-Bio reduced the viability of the tachyzoites and did not exhibit cytotoxicity against Leydig cells at low concentrations. Additionally, treatment with AgNp-Bio reduced the rate of infection and proliferation of the parasite, and lowered the testosterone levels in the infected cells. It increased the levels of IL-6 and TNF-α and reduced the levels of IL- 10. Among the morphological and ultrastructural changes, AgNp-Bio induced a reduction in the number of intracellular tachyzoites and caused changes in the tachyzoites with accumulation of autophagic vacuoles and a decrease in the number of tachyzoites inside the parasitophorous vacuoles. Collectively, our data demonstrate that the AgNp-Bio affect T. gondii tachyzoites by activating microbicidal and inflammatory mechanisms and could be a potential alternative treatment for toxoplasmosis.
Asunto(s)
Nanopartículas del Metal , Toxoplasma , Toxoplasmosis , Humanos , Interleucina-6 , Células Intersticiales del Testículo , Masculino , Nanopartículas del Metal/uso terapéutico , Nanopartículas del Metal/toxicidad , Plata/toxicidad , Testosterona , Factor de Necrosis Tumoral alfaRESUMEN
Because lignin is a macromolecule that is a sustainable source of aromatic compounds, model substrates are commonly used to increase our understanding of its complex structure. However, few methods have been described for the synthesis of these models. Herein, we describe a new route towards the synthesis of ß-O-4 lignin models by intermolecular O-H insertion reactions with simple and stable diazocarbonyls. The benefits of this developed method were shorter reaction times and high yields, as well as mild and environmentally friendly conditions.
RESUMEN
Cellular prion protein (PrPC ) is widely expressed and displays a variety of well-described functions in the central nervous system (CNS). Mutations of the PRNP gene are known to promote genetic human spongiform encephalopathies, but the components of gain- or loss-of-function mutations to PrPC remain a matter for debate. Among the proteins described to interact with PrPC is Stress-inducible protein 1 (STI1), a co-chaperonin that is secreted from astrocytes and triggers neuroprotection and neuritogenesis through its interaction with PrPC . In this work, we evaluated the impact of different PrPC pathogenic point mutations on signaling pathways induced by the STI1-PrPC interaction. We found that some of the pathogenic mutations evaluated herein induce partial or total disruption of neuritogenesis and neuroprotection mediated by mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases 1 and 2 (ERK1/2) and protein kinase A (PKA) signaling triggered by STI1-PrPC engagement. A pathogenic mutant PrPC that lacked both neuroprotection and neuritogenesis activities fail to promote negative dominance upon wild-type PrPC . Also, a STI1-α7-nicotinic acetylcholine receptor-dependent cellular signaling was present in a PrPC mutant that maintained both neuroprotection and neuritogenesis activities similar to what has been previously observed by wild-type PrPC . These results point to a loss-of-function mechanism underlying the pathogenicity of PrPC mutations.
Asunto(s)
Proteínas de Choque Térmico/metabolismo , Neuronas/patología , Proteínas PrPC/genética , Proteínas PrPC/metabolismo , Transducción de Señal/fisiología , Animales , Diferenciación Celular/genética , Línea Celular , Supervivencia Celular/genética , Ratones , Mutación , Neuronas/metabolismo , Proteínas Priónicas/genética , Proteínas Priónicas/metabolismoRESUMEN
OBJECTIVE: Several studies have shown that spiritual/religious beliefs are associated with mental health and quality of life. However, so far, no study assessed the relationship between spiritual/religious coping (SRC) and depressive symptoms in family caregivers (FCs) of pediatric cancer patients, particularly in Latin America. This study aimed to investigate whether Positive and Negative SRC strategies are associated with depressive symptoms in FCs of pediatric cancer patients in Brazil. METHODS: We conducted a cross-sectional study comprising 77 FCs of pediatric cancer patients from one Brazilian Pediatric Oncology Institute. Spiritual/religious coping was assessed using the Brief SRC scale, and depressive symptoms were evaluated by the Beck Depression Inventory. Multiple regression models were performed to identify factors associated with SRC of FCs and their depressive symptoms. RESULTS: In the unadjusted linear regression models, depressive symptoms were positively associated with Negative SRC (B = 0.401; P < .001; Adjusted R2 = 16.1%) but not with Positive SRC (B = 0.111; P = .334). After adjusting for socio-demographics, religious practice/faith, and health, Negative SRC remained associated with depressive symptoms (B = 3.56; P = .01; Adjusted R2 = 37.8%). In the logistic regression models, depressive symptoms were positively associated with Negative SRC (OR = 3.68; 95% CI, 1.46-9.25; P = .006), but not with Positive SRC (OR = 1.49; 95% CI, .69-3.22; P = .309). After adjustments, Negative SRC remained significant (OR = 4.01; 95% CI, 1.21-13.33; P = .023). CONCLUSIONS: Negative SRC was associated with depressive symptoms in FCs of pediatric cancer patients. Health professionals must be aware of the use of Negative SRC strategies in oncology care.
Asunto(s)
Adaptación Psicológica , Cuidadores/psicología , Depresión/psicología , Familia/psicología , Neoplasias/enfermería , Religión y Psicología , Adolescente , Adulto , Brasil , Niño , Estudios Transversales , Femenino , Humanos , América Latina , Masculino , Persona de Mediana Edad , Espiritualidad , Adulto JovenRESUMEN
Systemic arterial hypertension has been associated with the majority deaths from cardiovascular disease, especially among the elderly population, and the imbalance between antioxidant and pro-oxidants has been associated with hypertension. This study analyzed the acute responses of cardiorespiratory and oxidative stress parameters to low intensity aerobic exercise (LIAE) with blood flow restriction (BFR) in hypertensive elderly women. The experimental group consisted of 16 hypertensive women (67.2 ± 3.7 years) who underwent a progressive treadmill test and performed three exercise protocols in random order: high intensity (HIAE), low intensity aerobic exercise (LIAE) and low intensity aerobic exercise with blood flow restriction (LIAE + BFR). Data analysis showed that blood pressure and heart rate augmented from rest to post effort (p < 0.05) and reduced from post effort to recovery (p < 0.05) in all protocols. The values of lipid peroxidation were higher after 30 min of recovery when compared to the moment at rest in the LILIAE + BFR (p < 0.05). The same occurred with glutathione-S-transferase and superoxide dismutase activity. However, non-protein thiols levels (NPSH) reduced after 30 min of recovery when compared to the moment at rest in the LILIAE + BFR protocol (p < 0.05). In the HIAE and LIAE + BFR protocols, the levels of NPSH were lower at 30 min of recovery when compared to the same moment in the LIAE protocol (p < 0.05). LIAE + RBF produces an oxidative status and hemodynamic stimulus similar to HIAE. Taken together, these results support the indication of LIAE with BFR in chronic intervention protocols, with potential benefits for the hypertensive elderly population.
Asunto(s)
Hipertensión/metabolismo , Hipertensión/fisiopatología , Estrés Oxidativo , Entrenamiento de Fuerza/métodos , Anciano , Estudios Cruzados , Ejercicio Físico , Femenino , Frecuencia Cardíaca , Hemodinámica , Humanos , Hipertensión/sangre , Peroxidación de Lípido , Persona de Mediana Edad , Flujo Sanguíneo RegionalRESUMEN
The aim of this case report is to describe the treatment of a 9-year-old patient who suffered external root resorption of the permanent maxillary left lateral incisor following reimplantation of the avulsed left central and lateral incisors. Sixteen days after reimplantation and splinting of the incisors in a hospital emergency department, the patient was brought to the pediatric department of a dental school for further treatment. Root canal access was created in the maxillary left lateral and central incisors, and calcium hydroxide paste was used as intracanal dressing. At the 5-month follow-up, a radiograph revealed extensive external root resorption, a communicating root canal, and a periodontal lesion affecting the left lateral incisor. Management of the root resorption included obturation of the apical third of the canal with gutta percha and the middle third with mineral trioxide aggregate (MTA). At the 3-year recall examination, the patient was asymptomatic, and no mobility or soft tissue alterations were observed clinically. There was no radiographic sign that resorption had progressed. Despite the success of treatment, observation is still required. The use of MTA may be considered an alternative treatment for external root resorption after tooth reimplantation. The technique may allow tooth preservation in children until skeletal growth and development are completed and implant treatment may be considered.
Asunto(s)
Resorción Radicular/terapia , Avulsión de Diente/cirugía , Reimplante Dental/métodos , Niño , Femenino , Estudios de Seguimiento , Humanos , Radiografía Dental , Resorción Radicular/diagnóstico por imagen , Reimplante Dental/efectos adversosRESUMEN
The treatment of white-spot lesions in infants and young children with early childhood caries is a challenge. The ideal management of the disease and subsequent remineralization of the lesions depend on the family's commitment to dietary behavior modifications to address the causes of the disease. If this proves ineffective or unlikely, resin infiltration has been developed to slow or arrest progression of white-spot lesions. In resin infiltration, the porous lesion body is penetrated by a special low-viscosity resin, blocking the diffusion of cariogenic acids into the lesion. This case report describes the use of a resin infiltrant to treat white-spot lesions in a 24-month-old boy with early childhood caries.
Asunto(s)
Caries Dental/terapia , Resinas Sintéticas/uso terapéutico , Preescolar , Atención Dental para Niños/métodos , Humanos , Masculino , Higiene Bucal , Resinas Sintéticas/administración & dosificaciónRESUMEN
BACKGROUND: Care can be considered a lifelong process, but caring for a child is different from caring for an older adult. The present study aims to compare the caregiving process from infancy through old age by evaluating differences in caregiver burden, mental health, and quality of life and to describe the factors that could impact these outcomes. METHODS: To compare different groups of caregivers, we included 300 caregivers recruited from admissions to a tertiary acute hospital: 100 caregivers of children, 100 caregivers of adults, and 100 caregivers of older adults. A self-administered questionnaire was used that covered the following: sociodemographics, depression (Beck Depression Inventory), anxiety (Beck Anxiety Inventory), quality of life (Short Form Health Survey (SF-36)), religiosity (Duke Religion Index) and caregiver burden (Zarit Caregiver Burden Interview). RESULTS: A comparison between groups was performed (through χ2 and anova), and a linear regression analysis was used to assess the related factors. We found that children's caregivers had more depressive symptoms (higher Beck Depression Inventory scores), better physical health (SF-36: physical functioning and SF-36: Physical Component Summary), and lower pain (SF-36: bodily pain) than other caregivers. We found that caregivers of adults had better mental health (SF-36: mental health and SF-36: Mental Component Summary) than other caregivers and that caregivers of older adult had a higher caregiver burden (Zarit Caregiver Burden Interview scores) than other caregivers. After we controlled for baseline characteristics, only depressive symptoms and caregiver burden remained statistically significant. CONCLUSION: In conclusion, there are important differences between caregiving across the lifespan. Caregiving for children was associated with more depressive symptoms, and caregiving for older adults was associated with higher caregiver burden. Further studies are needed to replicate these findings in other settings.
RESUMEN
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by loss of motor neurons. Familial ALS is strongly associated to dominant mutations in the gene for Cu/Zn superoxide dismutase (SOD1). Recent evidences point to skeletal muscle as a primary target in the ALS mouse model. Wnt/PI3 K signaling pathways and epithelial-mesenchymal transition (EMT) have important roles in maintenance and repair of skeletal muscle. Wnt/PI3 K pathways and EMT gene expression profile were investigated in gastrocnemius muscle from SOD1(G93A) mouse model and age-paired wild-type control in the presymptomatic ages of 40 and 80 days aiming the early neuromuscular abnormalities that precede motor neuron death in ALS. A customized cDNA microarray platform containing 326 genes of Wnt/PI3 K and EMT was used and results revealed eight up-regulated (Loxl2, Pik4ca, Fzd9, Cul1, Ctnnd1, Snf1lk, Prkx, Dner) and nine down-regulated (Pik3c2a, Ripk4, Id2, C1qdc1, Eif2ak2, Rac3, Cds1, Inppl1, Tbl1x) genes at 40 days, and also one up-regulated (Pik3ca) and five down-regulated (Cd44, Eef2 k, Fzd2, Crebbp, Piki3r1) genes at 80 days. Also, protein-protein interaction networks grown from the differentially expressed genes of 40 and 80 days old mice have identified Grb2 and Src genes in both presymptomatic ages, thus playing a potential central role in the disease mechanisms. mRNA and protein levels for Grb2 and Src were found to be increased in 80 days old ALS mice. Gene expression changes in the skeletal muscle of transgenic ALS mice at presymptomatic periods of disease gave further evidence of early neuromuscular abnormalities that precede motor neuron death. The results were discussed in terms of initial triggering for neuronal degeneration and muscle adaptation to keep function before the onset of symptoms.
Asunto(s)
Esclerosis Amiotrófica Lateral/enzimología , Modelos Animales de Enfermedad , Regulación Enzimológica de la Expresión Génica , Músculo Esquelético/enzimología , Superóxido Dismutasa/biosíntesis , Esclerosis Amiotrófica Lateral/patología , Animales , Línea Celular , Humanos , Masculino , Ratones , Ratones Transgénicos , Músculo Esquelético/patologíaRESUMEN
The objective of this study was to evaluate the infection of domestic rabbits by Paracoccidioides brasiliensis. Initially two rabbits were experimentally infected with P. brasiliensis and the humoral immune response was evaluated by ELISA using gp43 as antigen. The two animals showed IgG response against gp43 although no signs of disease were observed. The seroepidemiological study was carried out in 170 rabbits (free range n = 81 and caged n = 89) living in an endemic area for human paracoccidioidomycosis and a positivity of 27% was observed in the ELISA using gp43 as antigen. The free-range rabbits showed a significantly higher positivity (34.6-51.7%) than the caged animals (11.1%). Sentinel rabbits exposed to natural infection with P. brasiliensis were followed up for 6 months and a seroconversion rate of 83.3% was observed. This is the first report of paracoccidioidomycosis in rabbits and suggests that this species can be useful sentinels for P. brasiliensis presence in the environment.
Asunto(s)
Anticuerpos Antifúngicos/sangre , Paracoccidioides/inmunología , Paracoccidioidomicosis/veterinaria , Enfermedades de los Roedores/epidemiología , Enfermedades de los Roedores/microbiología , Animales , Antígenos Fúngicos , Ensayo de Inmunoadsorción Enzimática , Femenino , Masculino , Paracoccidioides/aislamiento & purificación , Paracoccidioidomicosis/epidemiología , Paracoccidioidomicosis/microbiología , Conejos , Estudios SeroepidemiológicosRESUMEN
Paracoccidioidomycosis, caused by the thermodimorphic fungus Paracoccidioides brasiliensis, is a human systemic mycosis prevalent in Latin America. Paracoccidioidomycosis affects mainly male rural workers, causing granulomatous lesions in several organs such as the lungs, liver and spleen. The participation of other animal species in the fungus epidemiology is not well understood. The objective of this study was to evaluate the infection of free-range domestic pigs by P. brasiliensis. Serum samples from 106 pigs were analyzed by ELISA and the immunodiffusion test, using P. brasiliensis gp43 and exoantigen as antigens, respectively. The overall positivity to gp43 in ELISA was 37.7 %, although no reactivity was observed in the immunodiffusion test and nor was P. brasiliensis detected in tissue samples (spleen, lung, liver and lymph nodes) from slaughtered animals submitted to culture, histopathological examination and PCR analysis. Five pigs seronegative to gp43 were exposed to natural infection by P. brasiliensis, and all animals seroconverted 3 months after exposure. The results suggest that free-range pigs are frequently infected with P. brasiliensis but are resistant to disease development. This is the first report of paracoccidioidomycosis in pigs.
Asunto(s)
Anticuerpos Antifúngicos/sangre , Paracoccidioides/inmunología , Paracoccidioidomicosis/epidemiología , Paracoccidioidomicosis/veterinaria , Animales , Anticuerpos/sangre , Anticuerpos/inmunología , Antígenos Fúngicos/inmunología , Resistencia a la Enfermedad/inmunología , Ensayo de Inmunoadsorción Enzimática/veterinaria , Femenino , Proteínas Fúngicas/inmunología , Glicoproteínas/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Masculino , Paracoccidioidomicosis/sangre , Paracoccidioidomicosis/inmunología , Estudios Seroepidemiológicos , Sus scrofa , Porcinos/sangre , Porcinos/inmunología , Porcinos/microbiología , Enfermedades de los Porcinos/sangre , Enfermedades de los Porcinos/epidemiología , Enfermedades de los Porcinos/inmunologíaRESUMEN
PURPOSE: To evaluate the effects of toothbrushing abrasion associated with pH cycling on the surface roughness and wear of methacrylate- and silorane-based resin composites. METHODS: Microhybrid methacrylate-based (Filtek Z250), nanofilled methacrylate-based (Filtek Supreme Ultra) and microhybrid silorane-based (Filtek LS) composites were selected for this investigation. For each composite, two groups (n = 10) of rectangular specimens were made. The initial roughness (Ra) of all of the groups was evaluated based on the average of three random tracings with a profilometer, and each specimen had half of its surface protected with two layers of nail varnish to serve as controls. Half of the specimens of each resin were submitted to pH cycling, while the other half were stored in deionized water for 14 days. Subsequently, 100,000 strokes of simulated toothbrushing were performed. Final roughness and wear were measured with the same profilometer, and the values were submitted to ANOVA, Student's t-test and Tukey's test (P < 0.05). RESULTS: The data revealed an increase in surface roughness for Filtek Z250 and Filtek Supreme Ultra after toothbrushing, while Filtek LS showed the opposite behavior. Methacrylate-based composites presented lower wear values [Z250 (4.19 ± 1.73 µm); Supreme Ultra (4.16 ± 0.95 µm)], while the silorane-based composite presented increased surface roughness (11.51 ± 5.69 µm), particularly when submitted to pH cycling (15.31 ± 5.41 µm). Despite the good properties of silorane-based composites, particularly its smooth surface roughness even after pH cycling and toothbrushing abrasion, this composite still presented increased wear, which is an important issue for the development of new resin compositions.
Asunto(s)
Resinas de Silorano , Cepillado Dental , Concentración de Iones de Hidrógeno , Propiedades de SuperficieRESUMEN
BACKGROUND & AIMS: Ultrasonography (US) is a promising tool for assessing body composition, offering accuracy and accessibility. However, technician skills and equipment characteristics can impact measurement reliability. We aimed to evaluate the intra- and inter-rater reliability of two evaluators using A-mode Portable Ultrasound to measure muscle and fat thickness in Brazilian older adults. METHODS: Quantitative cross-sectional study carried out with 150 community-dwelling older adults of Campinas-SP-Brazil, recruited in a retirement preparation program and a geriatric outpatient care unit. Scans of nine anatomical points were performed using the portable ultrasound in A-mode (BodyMetrix Pro System BX2000; Livermore, CA), with 6 scans per location and 3 measurements taken by each evaluator. After the selection and analysis of the generated images, muscle and fat thickness were measured. Reliability estimates between measures of the same evaluator (intra-rater) and between evaluators (inter-rater) were assessed using intraclass correlation coefficients (ICC), and differences within and between technicians were assessed using one-way ANOVA. Analyses were carried out for the overall sample and stratified by sex and by nutritional status. RESULTS: Excellent ICC values (>0.90) were found for subcutaneous fat thickness in intra- and inter-rater reliability analyses. The lowest ICC values were observed for deep abdominal fat thickness measured by evaluator 1 (ICC = 0.90) and evaluator 2 (ICC = 0.87), as well as in the inter-rater analysis (ICC = 0.85). Muscle thickness measurements had satisfactory ICC values for triceps, biceps, anterior thigh, and calf, ranging from moderate to good (ICC 0.50-0.90). CONCLUSION: A portable A-mode ultrasound demonstrates excellent reliability among both intra- and inter-raters for assessing fat thickness but only moderate for muscle thickness in older adults. Hence, this could prompt inquiries regarding the sole reliance on this tool for quantifying muscle mass and examining sarcopenia in older adults. To our knowledge, this study represents the first assessment of reliability for a portable A-mode ultrasound device conducted with older adults.
Asunto(s)
Músculo Esquelético , Grasa Subcutánea , Humanos , Anciano , Reproducibilidad de los Resultados , Estudios Transversales , Ultrasonografía/métodos , Músculo Esquelético/diagnóstico por imagenRESUMEN
The disability of cells to react to insulin, causing glucose intolerance and hyperglycemia, is referred to as insulin resistance. This clinical condition, which has been well-researched in organs such as adipose tissue, muscle, and liver, has been linked to neurodegenerative diseases like Alzheimer's disease (AD) when it occurs in the brain. Objective: The authors aimed to gather data from the current literature on brain insulin resistance (BIR) and its likely repercussions on neurodegenerative disorders, more specifically AD, through a systematic review. Methods: A comprehensive search was conducted in multiple medical databases, including the Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online (Medline), and PubMed®, employing the descriptors: "insulin resistance", "brain insulin resistance", "Alzheimer's disease", "neurodegeneration", and "cognition". The authors focused their search on English-language studies published between 2000 and 2023 that investigated the influence of BIR on neurodegenerative disorders or offered insights into BIR's underlying mechanisms. Seventeen studies that met the inclusion criteria were selected. Results: The results indicate that BIR is a phenomenon observed in a variety of neurodegenerative disorders, including AD. Studies suggest that impaired glucose utilization and uptake, reduced adenosine triphosphate (ATP) production, and synaptic plasticity changes caused by BIR are linked to cognitive problems. However, conflicting results were observed regarding the association between AD and BIR, with some studies suggesting no association. Conclusion: Based on the evaluated studies, it can be concluded that the association between AD and BIR remains inconclusive, and additional research is needed to elucidate this relationship.
A incapacidade das células de reagir à insulina, ocasionando intolerância à glicose e hiperglicemia, é chamada de resistência à insulina. Essa condição clínica, que tem sido bem pesquisada em órgãos como tecido adiposo, músculo e fígado, tem sido associada às doenças neurodegenerativas como a doença de Alzheimer (DA) quando ocorre no cérebro. Objetivo: O objetivo dos autores foi reunir os dados da literatura atual sobre a resistência insulínica cerebral (RIC) e sua provável repercussão em doenças neurodegenerativas, mais especificamente na DA, por meio de uma revisão sistemática da literatura. Métodos: Foi realizada uma pesquisa abrangente em vários bancos de dados médicos, incluindo o Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online (Medline) e PubMed, empregando os descritores: "resistência à insulina", "resistência insulínica cerebral", "doença de Alzheimer", "neurodegeneração" e "cognição". Os autores concentraram sua busca em estudos no idioma inglês publicados entre 2000 e 2023 que investigaram a influência da RIC em distúrbios neurodegenerativos ou ofereceram insights sobre os mecanismos subjacentes da RIC. Dezessete estudos que atenderam aos critérios de inclusão foram selecionados. Resultados: Os resultados demonstram que a RIC é um fenômeno observado em uma variedade de doenças neurodegenerativas, incluindo a DA. Estudos sugerem que a utilização e captação prejudicadas de glicose, a produção reduzida de trifosfato de adenosina (ATP) e as alterações na plasticidade sinápticas causadas pela RIC estão ligadas a problemas cognitivos. No entanto, foram observados resultados conflitantes com relação à associação entre DA e RIC, com alguns estudos sugerindo nenhuma associação. Conclusão: Com base nos estudos avaliados, pode-se concluir que a associação entre DA e RIC ainda é inconclusiva, e pesquisas adicionais são necessárias para elucidar essa relação.
RESUMEN
BACKGROUND/OBJECTIVES: Strength and muscle mass are key factors for the diagnosis of sarcopenia. The EWGSOP2 recommended using ultrasound (US) as a reliable device to measure muscle mass (MM), but A-mode US still needs to be validated for older adults. This study aimed to evaluate the association between measurements of muscle thickness (MT) by portable A-mode US and, muscle quantity by Dual-Energy X-ray absorptiometry (DXA) in older adults. METHODS: Cross-sectional study, with 115 participants included. Muscle mass was assessed by DXA and MT of the biceps, triceps, anterior thigh, and calf by A-mode US and handgrip strength by a dynamometer. RESULTS: The majority were women (n = 96; 83%), 69 ± 6 years. The MT sum (biceps, triceps, thigh, and calf) assessed by the US was not associated with the appendicular lean mass (ALM) assessed by DXA after controlling for sex and age (R2 = 0.524; p = 0.139; effect size = 0.53). The MT sum biceps and triceps was still significantly associated with MM arms/2 even when controlling for sex and age (which were also significant) (R2 = 0.551; p < 0.001; effect size = 0.56). The MT sum thigh and calf was not associated with MM legs/2 in adjusted models (R2 = 0.499; p = 0.688; effect size = 0.51). CONCLUSIONS: This finding shows that the portable A-mode US may not be an appropriate method for estimating MM in extremities (the sum of arms and legs), but can be appropriate for estimating only MM arms in healthy older adults.
RESUMEN
Objective: To analyze in silico the evidence of molecular mimicry between human beta-cell autoantigens and cow's milk proteins as a potential type 1 diabetes mellitus (T1DM) trigger. Materials and methods: The in silico analysis was performed using bioinformatics tools to compare the amino acid sequences of cow's milk proteins (bovine serum albumin [BSA] and beta-lactoglobulin [BLG]) and human beta-cell autoantigens (glutamic acid decarboxylase-65 [GAD-65], insulin, and zinc transporter 8 [ZnT8]). The structural and functional characteristics of the proteins were analyzed to identify potential molecular mimicry mechanisms. Results: The results of the in silico analysis showed significant sequence similarity between BSA/BLG and GAD-65/human insulin/ZnT8, ranging from 19.64% to 27.27%. The cow's milk proteins evaluated shared structural features with the beta-cell antigens selected for comparison, indicating a potential for molecular mimicry between these proteins. Conclusion: The findings of this study provide further evidence for a potential role of cow's milk proteins in triggering T1DM. The in silico analysis suggests that molecular mimicry mechanisms between cow's milk proteins and human beta-cell antigens may contribute to the autoimmune response leading to T1DM.
Asunto(s)
Diabetes Mellitus Tipo 1 , Células Secretoras de Insulina , Proteínas de la Leche , Diabetes Mellitus Tipo 1/inmunología , Humanos , Animales , Bovinos , Proteínas de la Leche/inmunología , Células Secretoras de Insulina/inmunología , Lactoglobulinas/inmunología , Imitación Molecular/inmunología , Insulina , Autoantígenos/inmunología , Transportador 8 de Zinc/inmunología , Glutamato Descarboxilasa/inmunología , Simulación por Computador , Secuencia de Aminoácidos , Albúmina Sérica Bovina/inmunología , Biología ComputacionalRESUMEN
BACKGROUND: Feline obesity is the most common nutritional disease in cats. This study aimed to investigate the differences between systolic blood pressure (SBP) and circulating concentrations of glucose, fructosamine, and serum amyloid-A (SAA) in ideal-weight, overweight, and obese cats. METHODS: The animals were divided into three groups: ideal-weight (BCS 5, N = 20), overweight (BCS 6, N = 20), and obese cats (BCS ≥ 7, N = 20). SBP, circulating concentrations of glucose, fructosamine, and SAA were evaluated. RESULTS: The SBP values of the ideal-weight, overweight, and obese cats were 140.0 mmHg, 160.0 mmHg, and 160.0 mmHg, respectively. The blood glucose and fructosamine levels for the ideal, overweight, and obese cats were 104.0 mg/dL and 245.0 µmol/L, 123.0 mg/dL and 289.0 µmol/L, and 133.0 mg/dL and 275.0 µmol/L, respectively, for each group. The SAA values were <5 ug/mL in all the groups. The SBP values of the cats with ideal BCS were significantly lower compared to overweight (p = 0.019) and obese (p = 0.001) cats. The blood glucose values of obese cats were higher than those of ideal-weight cats (p = 0.029). There was no statistical difference between the groups for fructosamine and SAA. CONCLUSIONS: Obese cats had significantly higher SBP and blood glucose concentrations than ideal-weight cats, showing the effect of BSC on these parameters.
RESUMEN
Photodynamic therapy (PDT) utilizes the potential of photosensitizing substances to absorb light energy and produce reactive oxygen species. Tetra-cationic porphyrins, which have organic or coordination compounds attached to their periphery, are heterocyclic derivatives with well-described antimicrobial and antitumoral properties. This is due to their ability to produce reactive oxygen species and their photobiological properties in solution. Consequently, these molecules are promising candidates as new and more effective photosensitizers with biomedical, environmental, and other biomedical applications. Prior to human exposure, it is essential to establish the toxicological profile of these molecules using in vivo models. In this study, we used Caenorhabditis elegans, a small free-living nematode, as a model for assessing toxic effects and predicting toxicity in preclinical research. We evaluated the toxic effects of porphyrins (neutral and tetra-cationic) on nematodes under dark/light conditions. Our findings demonstrate that tetra-methylated porphyrins (3TMeP and 4TMeP) at a concentration of 3.3⯵g/mL (1.36 and 0.93⯵M) exhibit high toxicity (as evidenced by reduced survival, development, and locomotion) under dark conditions. Moreover, photoactivated tetra-methylated porphyrins induce higher ROS levels compared to neutral (3TPyP and 4TPyP), tetra-palladated (3PdTPyP and 4PdTPyP), and tetra-platinated (3PtTPyP and 4PtTPyP) porphyrins, which may be responsible for the observed toxic effects.