RESUMEN
The COVID-19 pandemic emerged in the context of a parallel epidemic of information, namely an infodemic. With the development of vaccines occurring in record time, a disinformation campaign ensued rendering the infodemic ever more troubling. As COVID-19 had to be curbed with vaccines opinion pools and surveys indicated that a minority, but relevant, part of the general public had weakened trust in public health policies and also on governmental responses to the pandemic in general. This dissent in public opinion on pandemic response is interpreted in this chapter as a controversy related to the efficacy and risks associated to vaccines. Such controversy gained momentum partly because traditional scientific communication has been largely unidirectional rather than bi-directional. We propose to apply a novel biosocial technical perspective to examine the COVID-19 pandemic controversy and communication, articulating social, biological and technical issues. The interaction between COVID-19 and vaccines, i.e. artefact-biological interactions, resulted in vaccine development in record time. However, the interaction between social systems and vaccine as artefacts was plagued by partial public reluctance in their acceptance. This rendered communication efforts ever more relevant, bringing lessons related to the importance of a more fluid bi-directional communication in future disease epidemics.
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Vacunas contra la COVID-19 , COVID-19 , Opinión Pública , SARS-CoV-2 , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , COVID-19/virología , Vacunas contra la COVID-19/inmunología , SARS-CoV-2/inmunología , Pandemias/prevención & control , Comunicación , Salud Pública/métodosRESUMEN
OBJECTIVE: To assess whether the respiratory oxygenation index (ROX index) measured after the start of high-flow nasal cannula oxygen therapy can help identify the need for intubation in patients with acute respiratory failure due to coronavirus disease 2019. METHODS: This retrospective, observational, multicenter study was conducted at the intensive care units of six Brazilian hospitals from March to December 2020. The primary outcome was the need for intubation up to 7 days after starting the high-flow nasal cannula. RESULTS: A total of 444 patients were included in the study, and 261 (58.7%) were subjected to intubation. An analysis of the area under the receiver operating characteristic curve (AUROC) showed that the ability to discriminate between successful and failed high-flow nasal cannula oxygen therapy within 7 days was greater for the ROX index measured at 24 hours (AUROC 0.80; 95%CI 0.76 - 0.84). The median interval between high-flow nasal cannula initiation and intubation was 24 hours (24 - 72), and the most accurate predictor of intubation obtained before 24 hours was the ROX index measured at 12 hours (AUROC 0.75; 95%CI 0.70 - 0.79). Kaplan-Meier curves revealed a greater probability of intubation within 7 days in patients with a ROX index ≤ 5.54 at 12 hours (hazard ratio 3.07; 95%CI 2.24 - 4.20) and ≤ 5.96 at 24 hours (hazard ratio 5.15; 95%CI 3.65 - 7.27). CONCLUSION: The ROX index can aid in the early identification of patients with acute respiratory failure due to COVID-19 who will progress to the failure of high-flow nasal cannula supportive therapy and the need for intubation.
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COVID-19 , Cánula , Intubación Intratraqueal , Terapia por Inhalación de Oxígeno , Humanos , COVID-19/terapia , COVID-19/complicaciones , Intubación Intratraqueal/efectos adversos , Estudios Retrospectivos , Terapia por Inhalación de Oxígeno/métodos , Terapia por Inhalación de Oxígeno/instrumentación , Masculino , Femenino , Persona de Mediana Edad , Anciano , Brasil/epidemiología , Insuficiencia Respiratoria/terapia , Unidades de Cuidados Intensivos , SARS-CoV-2RESUMEN
The Glycine Transporter Type 1 (GlyT1) significantly impacts central nervous system functions, influencing glycinergic and glutamatergic neurotransmission. Bitopertin, the first GlyT1 inhibitor in clinical trials, was developed for schizophrenia treatment but showed limited efficacy. Despite this, bitopertin's repositioning could advance treating various pathologies. This study aims to understand bitopertin's mechanism of action using computational methods, exploring off-target effects, and providing a comprehensive pharmacological profile. Similarity Ensemble Approach (SEA) and SwissTargetPrediction initially predicted targets, followed by molecular modeling on SWISS-MODEL and GalaxyWeb servers. Binding sites were identified using PrankWeb, and molecular docking was performed with DockThor and GOLD software. Molecular dynamics analyses were conducted on the Visual Dynamics platform. Reverse screening on SEA and SwissTargetPrediction identified GlyT1 (SLC6A9), GlyT2 (SLC6A5), PROT (SLC6A7), and DAT (SLC6A3) as potential bitopertin targets. Homology modeling on SwissModel generated high-resolution models, optimized further on GalaxyWeb. PrankWeb identified similar binding sites in GlyT1, GlyT2, PROT, and DAT, indicating potential interaction. Docking studies suggested bitopertin's interaction with GlyT1 and proximity to GlyT2 and PROT. Molecular dynamics confirmed docking results, highlighting bitopertin's target stability beyond GlyT1. The study concludes that bitopertin potentially interacts with multiple SLC6 family targets, indicating a broader pharmacological property.
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Proteínas de Transporte de Glicina en la Membrana Plasmática , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Proteínas de Transporte de Glicina en la Membrana Plasmática/metabolismo , Proteínas de Transporte de Glicina en la Membrana Plasmática/antagonistas & inhibidores , Humanos , Sitios de Unión , Piperazinas/farmacología , Piperazinas/química , Simulación por Computador , Reposicionamiento de Medicamentos , SulfonasRESUMEN
INTRODUCTION: Leishmaniasis stands out as a public health problem in the state of Minas Gerais, Brazil, especially in the Midwest region. However, the entomological aspects in several municipalities remain unknown. Therefore, this study aimed to investigate the sand fly fauna in Bambuí, encompassing ecological dynamics and molecular detection of Leishmania. METHODS: Monthly collections were conducted using CDC light traps from September 2018 to August 2020 across 16 selected points with urban and rural characteristics, chosen based on the coverage area of the Municipal Health Department and the occurrence of canine and human visceral leishmaniasis (VL) cases. Ecological indices of the sand fly population (Chao1, Shannon, Simpson and Pielou) were assessed, and sand fly abundance was correlated to climatic variables (humidity, temperature and rainfall). RESULTS: A total of 8838 specimens representing 17 species within nine genera were collected (estimated species richness by Chao 1 estimator = 17; SE ± 1.8). Predominantly, Lutzomyia longipalpis, Nyssomyia whitmani and Evandromyia cortelezzii constituted approximately 98% of all captured sand flies. While species richness and diversity displayed variations throughout the study, a positive correlation emerged between temperature (p < 0.0001; r = 0.7767), monthly rainfall (p < 0.0001; r = 0.7810) and sand fly abundance. Molecular analysis revealed Leishmania DNA in 2.05% of female sand flies, with the presence of Leishmania infantum in Lu. longipalpis and both Le. infantum and Leishmania braziliensis in Ev. cortelezzii. CONCLUSIONS: The entomological data, coupled with the occurrence of autochthonous cases of canine visceral leishmaniasis, offer valuable insights for evidence-based strategies to prevent leishmaniasis in Bambuí.
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Insectos Vectores , Psychodidae , Animales , Psychodidae/parasitología , Brasil/epidemiología , Insectos Vectores/parasitología , Leishmania/aislamiento & purificación , Leishmania/genética , Leishmaniasis/epidemiología , Leishmaniasis/transmisión , Leishmaniasis/veterinaria , Perros , Humanos , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/parasitología , Leishmaniasis Visceral/epidemiología , Leishmaniasis Visceral/veterinaria , Leishmaniasis Visceral/transmisiónRESUMEN
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-ß, leading to N-methyl-D-aspartate (NMDA) receptor-dependent synaptic depression, spine elimination, and memory deficits. Glycine transporter type 1 (GlyT1) modulates glutamatergic neurotransmission via NMDA receptors (NMDAR), presenting a potential alternative therapeutic approach for AD. This study investigates the neuroprotective potential of GlyT1 inhibition in an amyloid-ß-induced AD mouse model. C57BL/6 mice were treated with N-[3-([1,1-Biphenyl]-4-yloxy)-3-(4-fluorophenyl)propyl]-N-methylglycine (NFPS), a GlyT1 inhibitor, 24 h prior to intrahippocampal injection of amyloid-ß. NFPS pretreatment prevented amyloid-ß-induced cognitive deficits in short-term and long-term memory, evidenced by novel object recognition and spatial memory tasks. Moreover, NFPS pretreatment curbed microglial activation, astrocytic reactivity, and subsequent neuronal damage from amyloid-ß injection. An extensive label-free quantitative UPLC-MSE proteomic analysis was performed on the hippocampi of mice treated with NFPS. In proteomics, KEGG enrichment analysis revealed increased in dopaminergic synapse, purine-containing compound biosynthetic process and long-term potentiation, and a reduction in Glucose catabolic process and glycolytic process pathways. The western blot analysis confirmed that NFPS treatment elevated BDNF levels, correlating with enhanced TRKB phosphorylation and mTOR activation. Moreover, NFPS treatment reduced the GluN2B expression after 6 h, which was associated with an increase on CaMKIV and CREB phosphorylation. Collectively, these findings demonstrate that GlyT1 inhibition by NFPS activates diverse neuroprotective pathways, enhancing long-term potentiation signaling and countering amyloid-ß-induced hippocampal damage.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Proteínas de Transporte de Glicina en la Membrana Plasmática , Hipocampo , Ratones Endogámicos C57BL , Fármacos Neuroprotectores , Animales , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/prevención & control , Péptidos beta-Amiloides/metabolismo , Masculino , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Ratones , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Proteínas de Transporte de Glicina en la Membrana Plasmática/antagonistas & inhibidores , Proteínas de Transporte de Glicina en la Membrana Plasmática/metabolismo , Modelos Animales de Enfermedad , Sarcosina/análogos & derivados , Sarcosina/farmacología , Sarcosina/uso terapéutico , Neuroprotección/efectos de los fármacos , Neuroprotección/fisiologíaAsunto(s)
Fármacos Dermatológicos , Isotretinoína , Tiña Versicolor , Humanos , Isotretinoína/uso terapéutico , Isotretinoína/administración & dosificación , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/uso terapéutico , Tiña Versicolor/tratamiento farmacológico , Tiña Versicolor/patología , Administración Oral , Enfermedad Crónica , Masculino , Resultado del Tratamiento , AdultoRESUMEN
The striatum, an essential component of the brain's motor and reward systems, plays a pivotal role in a wide array of cognitive processes. Its dysfunction is a hallmark of neurodegenerative diseases like Parkinson's disease (PD) and Huntington's disease (HD), leading to profound motor and cognitive deficits. These conditions are often related to excitotoxicity, primarily due to overactivation of NMDA receptors (NMDAR). In the synaptic cleft, glycine transporter type 1 (GlyT1) controls the glycine levels, a NMDAR co-agonist, which modulates NMDAR function. This research explored the neuroprotective potential of NFPS, a GlyT1 inhibitor, in murine models of striatal injury. Employing models of neurotoxicity induced by 6-hydroxydopamine (PD model) and quinolinic acid (HD model), we assessed the effectiveness of NFPS pre-treatment in maintaining the integrity of striatal neurons and averting neuronal degeneration. The results indicated that NFPS pre-treatment conferred significant neuroprotection, reducing neuronal degeneration, protecting dopaminergic neurons, and preserving dendritic spines within the striatum. Additionally, this pre-treatment notably mitigated motor impairments resulting from striatal damage. The study revealed that GlyT1 inhibition led to substantial changes in the ratios of NMDAR subunits GluN2A/GluN1 and GluN2B/GluN1, 24 h after NFPS treatment. These findings underscore the neuroprotective efficacy of GlyT1 inhibition, proposing it as a viable therapeutic strategy for striatum-related damage.
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Proteínas de Transporte de Glicina en la Membrana Plasmática , Enfermedad de Huntington , Ratones , Animales , Proteínas de Transporte de Glicina en la Membrana Plasmática/metabolismo , Sarcosina/farmacología , Neuroprotección , Glicina/farmacología , Cuerpo Estriado/metabolismo , Enfermedad de Huntington/tratamiento farmacológicoRESUMEN
The search for novel anticancer drugs is essential to expand treatment options, overcome drug resistance, reduce toxicity, promote innovation, and tackle the economic impact. The importance of these studies lies in their contribution to advancing cancer research and enhancing patient outcomes in the battle against cancer. Here, we developed new asymmetric hybrids containing two different naphthoquinones linked by a 1,2,3-1H-triazole nucleus, which are potential new drugs for cancer treatment. The antitumor activity of the novel compounds was tested using the breast cancer cell lines MCF-7 and MDA-MB-231, using the non-cancer cell line MCF10A as control. Our results showed that two out of twenty-two substances tested presented potential antitumor activity against the breast cancer cell lines. These potential drugs, named here 12g and 12h were effective in reducing cell viability and promoting cell death of the tumor cell lines, exhibiting minimal effects on the control cell line. The mechanism of action of the novel drugs was assessed revealing that both drugs increased reactive oxygen species production with consequent activation of the AMPK pathway. Therefore, we concluded that 12g and 12h are novel AMPK activators presenting selective antitumor effects.
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Antineoplásicos , Neoplasias de la Mama , Naftoquinonas , Humanos , Femenino , Células MCF-7 , Especies Reactivas de Oxígeno/metabolismo , Triazoles/farmacología , Naftoquinonas/farmacología , Proteínas Quinasas Activadas por AMP , Proliferación Celular , Apoptosis , Línea Celular Tumoral , Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Ensayos de Selección de Medicamentos AntitumoralesRESUMEN
The glutamatergic hypothesis of schizophrenia suggests a correlation between NMDA receptor hypofunction and negative psychotic symptoms. It has been observed that the expression of the proline transporter (PROT) in the central nervous system (CNS) is associated with glutamatergic neurotransmission, as L-proline has the capacity to activate and modulate AMPA and NMDA receptors. In this study, we aimed to investigate whether inhibition of proline transporters could enhance glutamatergic neurotransmission and potentially exhibit antipsychotic effects in an experimental schizophrenia model. Using molecular dynamics analysis in silico, we validated an innovative PROT inhibitor, LQFM215. We quantified the cytotoxicity of LQFM215 in the Lund human mesencephalic cell line (LUHMES). Subsequently, we employed the ketamine-induced psychosis model to evaluate the antipsychotic potential of the inhibitor, employing behavioral tests including open-field, three-chamber interaction, and prepulse inhibition (PPI). Our results demonstrate that LQFM215, at pharmacologically active concentrations, exhibited negligible neurotoxicity when astrocytes were co-cultured with neurons. In the ketamine-induced psychosis model, LQFM215 effectively reduced hyperlocomotion and enhanced social interaction in a three-chamber social approach task across all administered doses. Moreover, the compound successfully prevented the ketamine-induced disruption of sensorimotor gating in the PPI test at all tested doses. Overall, these findings suggest that PROT inhibition could serve as a potential therapeutic target for managing symptoms of schizophrenia model.
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Sistemas de Transporte de Aminoácidos Neutros , Antipsicóticos , Ketamina , Esquizofrenia , Humanos , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Esquizofrenia/inducido químicamente , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/metabolismo , Ketamina/farmacología , Ketamina/uso terapéutico , Sistemas de Transporte de Aminoácidos Neutros/uso terapéutico , Receptores de N-Metil-D-AspartatoRESUMEN
ABSTRACT Objective: To assess whether the respiratory oxygenation index (ROX index) measured after the start of high-flow nasal cannula oxygen therapy can help identify the need for intubation in patients with acute respiratory failure due to coronavirus disease 2019. Methods: This retrospective, observational, multicenter study was conducted at the intensive care units of six Brazilian hospitals from March to December 2020. The primary outcome was the need for intubation up to 7 days after starting the high-flow nasal cannula. Results: A total of 444 patients were included in the study, and 261 (58.7%) were subjected to intubation. An analysis of the area under the receiver operating characteristic curve (AUROC) showed that the ability to discriminate between successful and failed high-flow nasal cannula oxygen therapy within 7 days was greater for the ROX index measured at 24 hours (AUROC 0.80; 95%CI 0.76 - 0.84). The median interval between high-flow nasal cannula initiation and intubation was 24 hours (24 - 72), and the most accurate predictor of intubation obtained before 24 hours was the ROX index measured at 12 hours (AUROC 0.75; 95%CI 0.70 - 0.79). Kaplan-Meier curves revealed a greater probability of intubation within 7 days in patients with a ROX index ≤ 5.54 at 12 hours (hazard ratio 3.07; 95%CI 2.24 - 4.20) and ≤ 5.96 at 24 hours (hazard ratio 5.15; 95%CI 3.65 - 7.27). Conclusion: The ROX index can aid in the early identification of patients with acute respiratory failure due to COVID-19 who will progress to the failure of high-flow nasal cannula supportive therapy and the need for intubation.
RESUMO Objetivo: Avaliar se o índice de oxigenação respiratória medido após o início da terapia de oxigênio com cânula nasal de alto fluxo pode ajudar a identificar a necessidade de intubação em pacientes com insuficiência respiratória aguda devido à COVID-19. Métodos: Este estudo retrospectivo, observacional e multicêntrico foi realizado nas unidades de terapia intensiva de seis hospitais brasileiros, de março a dezembro de 2020. O desfecho primário foi a necessidade de intubação até 7 dias após o início da cânula nasal de alto fluxo. Resultados: O estudo incluiu 444 pacientes; 261 (58,7%) foram submetidos à intubação. Uma análise da área sob a curva receiver operating characteristic (ASC ROC) mostrou que a capacidade de discriminar entre o sucesso e o fracasso da oxigenoterapia com cânula nasal de alto fluxo dentro de 7 dias foi maior para o índice de oxigenação respiratória medido em 24 horas (ASC ROC 0,80; IC95% 0,76 - 0,84). O intervalo médio entre o início da cânula nasal de alto fluxo e a intubação foi de 24 horas (24 - 72), e o preditor mais preciso de intubação obtido antes de 24 horas foi o índice de oxigenação respiratória medido em 12 horas (ASC ROC 0,75; IC95% 0,70 - 0,79). As curvas de Kaplan-Meier revelaram maior probabilidade de intubação em 7 dias em pacientes com índice de oxigenação respiratória ≤ 5,54 em 12 horas (razão de risco 3,07; IC95% 2,24 - 4,20) e ≤ 5,96 em 24 horas (razão de risco 5,15; IC95% 3,65 - 7,27). Conclusões: O índice de oxigenação respiratória pode ajudar na identificação precoce de pacientes com insuficiência respiratória aguda devido à COVID-19 que evoluirão para o fracasso da terapia de suporte com cânula nasal de alto fluxo e a necessidade de intubação.
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The municipality of Salvador, situated in Brazil, distinguished itself as the epicenter of the emergence of microcephaly related to congenital manifestations of Zika syndrome. Despite the anticipated significant developmental setbacks in these children, research has indicated a varied range of outcomes, with certain instances even reflecting minimal developmental delay. Our objective was to pinpoint determinants that could forecast developmental anomalies in children diagnosed with microcephaly associated with congenital Zika syndrome (CZS). METHODOLOGY: A forward-looking clinical and neurodevelopmental examination was conducted focusing on neonates diagnosed with microcephaly with CZS, birthed between September 2015 and April 2016 at the Hospital Geral Roberto Santos, in Salvador city. That infants were monitored up to their third year by a multiprofessional team. Child development was assessed using the composite Bayley III score. Undertaken by two blinded experts, cranial CT scan analysis was performed during the neonate period for the detection of brain abnormalities and to quantify ventricle enlargement, measured by Evans' index (EI). RESULTS: Fifty newborns were evaluated with a median head circumference of 28 cm (interquartile range 27-31 cm). EI was associated with neurodevelopmental delay at three years and remained significant after adjustment for head circumference. A 0.1-point increase in EI was associated with a delay of 3.2 months in the receptive language (p = 0.016), 3.4 months in the expressive language (p = 0.016), 3.4 months in the cognitive (p = 0.016), 2.37 months in the gross motor (p = 0.026), and 3.1 months in the fine motor (p = 0.021) domains. CONCLUSIONS: EI predicted neurodevelopmental delay in all Bayley domains in children with microcephaly associated with CZS.
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Global navigation satellite systems (GNSSs) became an integral part of all aspects of our lives, whether for positioning, navigation, or timing services. These systems are central to a range of applications including road, aviation, maritime, and location-based services, agriculture, and surveying. The Global Positioning System (GPS) Standard Position Service (SPS) provides position accuracy up to 10 m. However, some modern-day applications, such as precision agriculture (PA), smart farms, and Agriculture 4.0, have demanded navigation technologies able to provide more accurate positioning at a low cost, especially for vehicle guidance and variable rate technology purposes. The Society of Automotive Engineers (SAE), for instance, through its standard J2945 defines a maximum of 1.5 m of horizontal positioning error at 68% probability (1σ), aiming at terrestrial vehicle-to-vehicle (V2V) applications. GPS position accuracy may be improved by addressing the common-mode errors contained in its observables, and relative GNSS (RGNSS) is a well-known technique for overcoming this issue. This paper builds upon previous research conducted by the authors and investigates the sensitivity of the position estimation accuracy of low-cost receiver-equipped agricultural rovers as a function of two degradation factors that RGNSS is susceptible to: communication failures and baseline distances between GPS receivers. The extended Kalman filter (EKF) approach is used for position estimation, based on which we show that it is possible to achieve 1.5 m horizontal accuracy at 68% probability (1σ) for communication failures up to 3000 s and baseline separation of around 1500 km. Experimental data from the Brazilian Network for Continuous Monitoring of GNSS (RBMC) and a moving agricultural rover equipped with a low-cost GPS receiver are used to validate the analysis.
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Changes in food quality can dramatically impair zooplankton fitness, especially in eutrophic water bodies where cyanobacteria are usually predominant. Cyanobacteria are considered a food with low nutritional value, and some species can produce bioactive secondary metabolites reported as toxic to zooplankton. Considering that cyanobacteria can limit the survival, growth and reproduction of zooplankton, we hypothesized that the dietary exposure of neotropical Daphnia species (D. laevis and D. gessneri) to saxitoxin-producing cyanobacteria impairs Daphnia feeding rates and fitness regardless of a high availability of nutritious algae. Life table and grazing assays were conducted with different diets: (1) without nutritional restriction, where neonates were fed with diets at a constant green algae biomass (as a nutritious food source), and an increasing cyanobacterial concentration (toxic and poor food source), and (2) with diets consisting of different proportions of green algae (nutritious) and cyanobacteria (poor food) at a total biomass 1.0 mg C L-1. In general, the presence of high proportions of cyanobacteria promoted a decrease in Daphnia somatic growth, reproduction and the intrinsic rate of population increase (r) in both diets with more pronounced effects in the nutritionally restricted diet (90% R. raciborskii). A two-way ANOVA revealed the significant effects of species/clone and treatments in both assays, with significant interaction between those factors only in the second assay. Regarding the grazing assay, only D. laevis was negatively affected by increased cyanobacterial proportions in the diet. In the life table assay with constant nutritious food, a reduction in the reproduction and the intrinsic rate of the population increase (r) of all species were observed. In conclusion, we found adverse effects of the toxic cyanobacterial strain R. raciborskii on Daphnia fitness, regardless of the constant amount of nutritious food available, proving the toxic effect of R. raciborskii and that the nutritional quality of the food has a greater influence on the fitness of these animals.
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BACKGROUND: L-proline transporter (PROT/SLC6A7) is closely associated with glutamatergic neurotransmission, where L-proline modulates the NMDA receptor (NMDAR) function. NMDAR-mediated excitotoxicity is a primary cause of neuronal death following stroke, which is triggered by the uncontrolled release of glutamate during the ischemic process. After ischemic stroke, L-proline levels show a reduction in the plasma, but high circulating levels of this molecule indicate good functional recovery. This work aimed to produce new PROT inhibitors and explore their effects on ischemic stroke. METHODS: Initially, we built a three-dimensional model of the PROT protein and run a molecular docking with the newly designed compounds (LQFM215, LQFM216, and LQFM217). Then, we synthesized new PROT inhibitors by molecular hybridization, and proline uptake was measured in ex vivo and in vivo models. The behavioral characterization of the treated mice was performed by the open-field test, elevated plus-maze, Y-maze, and forced swimming test. We used the permanent middle cerebral artery occlusion (MCAO) model to study the ischemic stroke damage and analyzed the motor impairment with limb clasping or cylinder tests. RESULTS: LQFM215 inhibited proline uptake in hippocampal synaptosomes, and the LQFM215 treatment reduced proline levels in the mouse hippocampus. LQFM215 reduced the locomotor and exploratory activity in mice and did not show any anxiety-related or working memory impairments. In the MCAO model, LQFM215 pre-treatment and treatment reduced the infarcted area and reduced motor impairments in the cylinder test and limb clasping. CONCLUSIONS: This dataset suggests that the new compounds inhibit cerebral L-proline uptake and that LQFM215 promotes neuroprotection and neuro-repair in the acute ischemic stroke model.