Systematic Review and Meta-Analyses of Aminopeptidases as Prognostic Biomarkers in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons in the spinal cord, brain stem, and cerebral cortex. Biomarkers for ALS are essential for disease detection and to provide information on potential therapeutic targets. Aminopeptidases catalyze the cleavage of amino acids from the amino terminus of protein or substrates such as neuropeptides. Since certain aminopeptidases are known to increase the risk of neurodegeneration, such mechanisms may reveal new targets to determine their association with ALS risk and their interest as a diagnostic biomarker. The authors performed a systematic review and meta-analyses of genome-wide association studies (GWASs) to identify reported aminopeptidases genetic loci associated with the risk of ALS. PubMed, Scopus, CINAHL, ISI Web of Science, ProQuest, LILACS, and Cochrane databases were searched to retrieve eligible studies in English or Spanish, published up to 27 January 2023. A total of 16 studies were included in this systematic review, where a series of aminopeptidases could be related to ALS and could be promising biomarkers (DPP1, DPP2, DPP4, LeuAP, pGluAP, and PSA/NPEPPS). The literature reported the association of single-nucleotide polymorphisms (SNPs: rs10260404 and rs17174381) with the risk of ALS. The genetic variation rs10260404 in the DPP6 gene was identified to be highly associated with ALS susceptibility, but meta-analyses of genotypes in five studies in a matched cohort of different ancestry (1873 cases and 1861 control subjects) showed no ALS risk association. Meta-analyses of eight studies for minor allele frequency (MAF) also found no ALS association for the "C" allele. The systematic review identified aminopeptidases as possible biomarkers. However, the meta-analyses for rs1060404 of DPP6 do not show a risk associated with ALS.

Polarimetric imaging for the detection of synthetic models of SARS-CoV-2: A proof of concept.

Objective: To conduct a proof-of-concept study of the detection of two synthetic models of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using polarimetric imaging. Approach: Two SARS-CoV-2 models were prepared as engineered lentiviruses pseudotyped with the G protein of the vesicular stomatitis virus, and with the characteristic Spike protein of SARS-CoV-2. Samples were prepared in two biofluids (saline solution and artificial saliva), in four concentrations, and deposited as 5-µL droplets on a supporting plate. The angles of maximal degree of linear polarization (DLP) of light diffusely scattered from dry residues were determined using Mueller polarimetry from87 samples at 405 nm and 514 nm. A polarimetric camera was used for imaging several samples under 380-420 nm illumination at angles similar to those of maximal DLP. Per-pixel image analysis included quantification and combination of polarization feature descriptors in 475 samples. Main results: The angles (from sample surface) of maximal DLP were 3° for 405 nm and 6° for 514 nm. Similar viral particles that differed only in the characteristic spike protein of the SARS-CoV-2, their corresponding negative controls, fluids, and the sample holder were discerned at 10-degree and 15-degree configurations. Significance: Polarimetric imaging in the visible spectrum may help improve fast, non-contact detection and identification of viral particles, and/or other microbes such as tuberculosis, in multiple dry fluid samples simultaneously, particularly when combined with other imaging modalities. Further analysis including realistic concentrations of real SARS-CoV-2 viral particles in relevant human fluids is required. Polarimetric imaging under visible light may contribute to a fast, cost-effective screening of SARS-CoV-2 and other pathogens when combined with other imaging modalities.

Polyphosphate Activates von Willebrand Factor Interaction with Glycoprotein Ib in the Absence of Factor VIII In Vitro.

Polyphosphate (polyP), a phosphate polymer released by activated platelets, may modulate various stages of hemostasis by binding to blood proteins. In this context, we previously reported that polyP binds to the von Willebrand factor (VWF). One of the most significant functions of VWF is to bind to and protect the blood circulating Factor VIII (FVIII). Therefore, here, we study the role of polyP in the VWF-FVIII complex in vitro and suggest its biological significance. Surface plasmon resonance and electrophoretic mobility assays indicated that polyP binds dynamically to VWF only in the absence of FVIII. Using the VWF Ristocetin Cofactor assay, the most accepted method for studying VWF in platelet adhesion, we found that polyP activates this role of VWF only at low levels of FVIII, such as in plasmas with chemically depleted FVIII and plasmas from severe hemophilia A patients. Moreover, we demonstrated that FVIII competes with polyP in the activation of VWF. Finally, polyP also increases the binding of VWF to platelets in samples from patients with type 2 and type 3 von Willebrand disease. We propose that polyP may be used in designing new therapies to activate VWF when FVIII cannot be used.

Therapeutic Approach to Alzheimer's Disease: Current Treatments and New Perspectives.

Alzheimer's disease (AD) is the most common cause of dementia. The pathophysiology of this disease is characterized by the accumulation of amyloid-ß, leading to the formation of senile plaques, and by the intracellular presence of neurofibrillary tangles based on hyperphosphorylated tau protein. In the therapeutic approach to AD, we can identify three important fronts: the approved drugs currently available for the treatment of the disease, which include aducanumab, donepezil, galantamine, rivastigmine, memantine, and a combination of memantine and donepezil; therapies under investigation that work mainly on Aß pathology and tau pathology, and which include γ-secretase inhibitors, ß-secretase inhibitors, α-secretase modulators, aggregation inhibitors, metal interfering drugs, drugs that enhance Aß clearance, inhibitors of tau protein hyperphosphorylation, tau protein aggregation inhibitors, and drugs that promote the clearance of tau, and finally, other alternative therapies designed to improve lifestyle, thus contributing to the prevention of the disease. Therefore, the aim of this review was to analyze and describe current treatments and possible future alternatives in the therapeutic approach to AD.

Optical imaging spectroscopy for rapid, primary screening of SARS-CoV-2: a proof of concept.

Effective testing is essential to control the coronavirus disease 2019 (COVID-19) transmission. Here we report a-proof-of-concept study on hyperspectral image analysis in the visible and near-infrared range for primary screening at the point-of-care of SARS-CoV-2. We apply spectral feature descriptors, partial least square-discriminant analysis, and artificial intelligence to extract information from optical diffuse reflectance measurements from 5 µL fluid samples at pixel, droplet, and patient levels. We discern preparations of engineered lentiviral particles pseudotyped with the spike protein of the SARS-CoV-2 from those with the G protein of the vesicular stomatitis virus in saline solution and artificial saliva. We report a quantitative analysis of 72 samples of nasopharyngeal exudate in a range of SARS-CoV-2 viral loads, and a descriptive study of another 32 fresh human saliva samples. Sensitivity for classification of exudates was 100% with peak specificity of 87.5% for discernment from PCR-negative but symptomatic cases. Proposed technology is reagent-free, fast, and scalable, and could substantially reduce the number of molecular tests currently required for COVID-19 mass screening strategies even in resource-limited settings.

Capacidad aeróbica, dieta mediterránea y riesgo cardiometabólico en adultos / Aerobic fitness, Mediterranean diet and cardiometabolic risk factors in adults

Introducción: Un estilo de vida poco activo y una dieta inadecuada podrían influir en el desarrollo de futuras enfermedades cardiometabólicas. El objetivo principal fue determinar la asociación entre capacidad aeróbica y factores de riesgo cardiometabólicos y si dicha posible asociación es independiente de la dieta mediterránea (DM). A su vez, se plantea como objetivo secundario estudiar el efecto combinado de la capacidad aeróbica y la adherencia a la DM sobre el índice de riesgo cardiometabólico global (IRCM) en adultos. Métodos: Se evaluó a 79 adultos (38% mujeres) entre 18 y 40 años en Cádiz. Se midieron indicadores de adiposidad, presión arterial, triglicéridos, glucosa y perfil inflamatorio (interleucina-6 y factor de necrosis tumoral) y se desarrolló un IRCM. Se midió la capacidad aeróbica mediante el consumo máximo de oxígeno a través de una prueba de esfuerzo incremental en cicloergómetro. La adherencia a la DM se evaluó mediante cuestionario. Se utilizó un modelo de regresión lineal para estudiar la asociación entre capacidad aeróbica y factores de riesgo cardiometabólicos con diferentes modelos de ajuste. Se analizó el efecto combinado de la capacidad aeróbica y la adherencia a la DM sobre el IRCM mediante el test de ANOVA, con nivel de significación de p < 0,05 en Bonferroni. Resultados: Se observó asociación negativa entre la capacidad aeróbica y los factores de riesgo cardiometabólicos (todas p ≤ 0,05) en el modelo sin ajustar. La presión arterial y los triglicéridos perdieron la asociación tras ajustar el modelo por sexo, edad y adherencia a la DM. Los participantes con alta capacidad aeróbica y alta adherencia a la DM mostraron un menor IRCM (-1,083 ± 2,325 vs. 2,802 ± 1,759). Conclusiones: La capacidad aeróbica se asocia de forma inversa con factores de riesgo cardiometabólicos relacionados con la adiposidad, independientemente de la adherencia a la DM. Una alta adherencia a la DM podría influir en la modulación de la presión arterial. Una alta capacidad aeróbica podría reducir las consecuencias adversas de una baja adherencia a la DM

Introduction: Unhealthy lifestyle and inadequate diet could influence the development of future cardiometabolic disease. The main aim of this study was to determine the association between aerobic fitness and cardiometabolic risk factors in adults, whether this relation is depends of adherence to Mediterranean diet (MD). A secondary aim was to study the combined effect of aerobic capacity and adherence to MD on global cardiometabolic risk score (CMRS). Method: A total of 79 adults (38% women) enrolled between 18-40 year from Cádiz. We measured adiposity indicators, blood pressure, triglycerides, glucose and inflammatory profile (interleukin-6 and tumor necrosis factor) and was computed (CMRS). Aerobic fitness was measured by maximal oxygen comsuption through an incremental stress test by cycleergometer. The MD patterns was measured using the questionnaire of adherence to MD. The association between aerobic fitness and cardiometabolic risk factors was examined using a lineal regression and it was adjusted for different confounders. CMRS on the lifestyle was analyzed using the ANOVA test, with statistical significance level of P < 0.05 in Bonferroni. Results: Linear regression showed inverse association between aerobic fitness and cardiometabolic risk factors (all P ≤ 0.05) in the model without adjustment. Blood pressure and triglycerides lost the association after adjust model for sex, age, and adherence to MD. Participants with high aerobic fitness and high adherence to MD show a lowest CMRS (-1.083 ± 2.325 vs. 2.802 ± 1.759). Conclusions: Aerobic fitness was inversely associated with fatness risk factors, that relationship is independent to adherence to MD. A high adherence to MD could modulate blood pressure. A combination of high aerobic capacity and high adherence to MD could reduce the adverse consecuence of a low adherencie to MD

Aerobic fitness, Mediterranean diet and cardiometabolic risk factors in adults. / Capacidad aeróbica, dieta mediterránea y riesgo cardiometabólico en adultos.

INTRODUCTION: Unhealthy lifestyle and inadequate diet could influence the development of future cardiometabolic disease. The main aim of this study was to determine the association between aerobic fitness and cardiometabolic risk factors in adults, whether this relation is depends of adherence to Mediterranean diet (MD). A secondary aim was to study the combined effect of aerobic capacity and adherence to MD on global cardiometabolic risk score (CMRS). METHOD: A total of 79 adults (38% women) enrolled between 18-40 year from Cádiz. We measured adiposity indicators, blood pressure, triglycerides, glucose and inflammatory profile (interleukin-6 and tumor necrosis factor) and was computed (CMRS). Aerobic fitness was measured by maximal oxygen comsuption through an incremental stress test by cycleergometer. The MD patterns was measured using the questionnaire of adherence to MD. The association between aerobic fitness and cardiometabolic risk factors was examined using a lineal regression and it was adjusted for different confounders. CMRS on the lifestyle was analyzed using the ANOVA test, with statistical significance level of P<0.05 in Bonferroni. RESULTS: Linear regression showed inverse association between aerobic fitness and cardiometabolic risk factors (all P≤0.05) in the model without adjustment. Blood pressure and triglycerides lost the association after adjust model for sex, age, and adherence to MD. Participants with high aerobic fitness and high adherence to MD show a lowest CMRS (-1.083±2.325 vs. 2.802±1.759). CONCLUSIONS: Aerobic fitness was inversely associated with fatness risk factors, that relationship is independent to adherence to MD. A high adherence to MD could modulate blood pressure. A combination of high aerobic capacity and high adherence to MD could reduce the adverse consecuence of a low adherencie to MD.

[Diet and exercise influence on the proteomic profile of an athlete population]. / Influencia de la dieta y el ejercicio en el perfil proteómico de una poblacion deportista.

INTRODUCTION: Nutrition has emerged as a fundamental tool included in the training program of athletes. Body composition seeks different objectives depending on type of sport, position, or time of the season. Furthermore, analysis proteomics allows us to know the structure and function of proteins. AIMS: To study, using proteomics, the influence of two different diets on the anthropometric profile in a rugby players group. METHODS: It is a prospective and interventionist study. Thirty-two rugby players were included. Two groups were defined, one followed proteic diet (PD) and, the other group subscribed the Mediterranean diet (MD). All participants were evaluated anthropometrically at the beginning and after six months. A blood sample was taken to twenty -two players, half of each group, used for the proteomic analysis. RESULTS: MD highlight more benefit for these athletes. Two groups were defined based on their anthropometric behavior, G1 and G2. The proteomic analysis related significantly some TGF-family mediators with these groups. CONCLUSIONS: MD improves the muscular mass without increasing the total body weight, so this data could be determinant to define profiles for athletes. Some TGF-members could be implicated in the adipose tissue and muscular mass balance.

Introducción: La nutrición se ha erigido como una herramienta fundamental incluida en el programa de entrenamiento de los deportistas. La composición corporal persigue diferentes objetivos según el deporte, la posición o momento de la temporada. Por otro lado, la proteómica permite analizar la estructura y función de las proteínas. Objetivos: Estudiar, utilizando la proteómica, la influencia de dos dietas diferentes sobre el perfil antropométrico en un grupo de jugadores de rugby. Metodos: Es un estudio prospectivo y de intervención. Treinta y dos jugadores de rugby fueron incluidos en el estudio. Se definieron dos grupos arbitrariamente, unos siguieron la dieta proteica (DP) y otros la dieta mediterránea (DM). A todos se les realizó una valoración antropométrica al inicio y tras seis meses de seguimiento. A 22 de estos pacientes, la mitad de cada grupo, se les tomo una muestra de sangre que se utilizó para el análisis proteómico. Resultados: La DM se destaca más beneficiosa para estos deportistas. Se definieron dos grupos en función de su comportamiento antropométrico, G1 and G2. En el análisis proteómico estos se relacionaron significativamente con varios mediadores de la familia TGF-. Conclusiones: La DM promociona el incremento de masa muscular sin incremento del peso total, ello podría ser determinante a la hora de definir los perfiles de los deportistas. Miembros de la familia TGF-podrían estar implicados en el balance de tejido adiposo y masa muscular.

Influencia de la dieta y el ejercicio en el perfil proteómico de una poblacion deportista / Diet and exercise influence on the proteomic profile of an atlete population

Introducción: La nutrición se ha erigido como una herramienta fundamental incluida en el programa de entrenamiento de los deportistas. La composición corporal persigue diferentes objetivos según el deporte, la posición o momento de la temporada. Por otro lado, la proteómica permite analizar la estructura y función de las proteínas. Objetivos: Estudiar, utilizando la proteómica, la influencia de dos dietas diferentes sobre el perfil antropométrico en un grupo de jugadores de rugby. Métodos: Es un estudio prospectivo y de intervención. Treinta y dos jugadores de rugby fueron incluidos en el estudio. Se definieron dos grupos arbitrariamente, unos siguieron la dieta proteica (DP) y otros la dieta mediterránea (DM). A todos se les realizó una valoración antropométrica al inicio y tras seis meses de seguimiento. A 22 de estos pacientes, la mitad de cada grupo, se les tomo una muestra de sangre que se utilizó para el análisis proteómico. Resultados: La DM se destaca más beneficiosa para estos deportistas. Se definieron dos grupos en función de su comportamiento antropométrico, G1 and G2. En el análisis proteómico estos se relacionaron significativamente con varios mediadores de la familia TGF-β. CONCLUSIONES: La DM promociona el incremento de masa muscular sin incremento del peso total, ello podría ser determinante a la hora de definir los perfiles de los deportistas. Miembros de la familia TGF-β podrían estar implicados en el balance de tejido adiposo y masa muscular (AU)

Introduction: Nutrition has emerged as a fundamental tool included in the training program of athletes. Body composition seeks different objectives depending on type of sport, position, or time of the season. Furthermore, analysis proteomics allows us to know the structure and function of proteins. Aims: To study, using proteomics, the influence of two different diets on the anthropometric profile in a rugby players group. Methods: It is a prospective and interventionist study. Thirty-two rugby players were included. Two groups were defined, one followed proteic diet (PD) and, the other group subscribed the Mediterranean diet (MD). All participants were evaluated anthropometrically at the beginning and after six months. A blood sample was taken to twenty-two players, half of each group, used for the proteomic analysis. Results: MD highlight more benefit for these athletes. Two groups were defined based on their anthropometric behavior, G1 and G2. The proteomic analysis related significantly some TGF-β family mediators with these groups. CONCLUSIONS: MD improves the muscular mass without increasing the total body weight, so this data could be determinant to define profiles for athletes. Some TGF- β members could be implicated in the adipose tissue and muscular mass balance (AU)