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Cauliflower (Brassica oleraceae L. var. Botrytis Linnaeus) has various health benefits due to its rich bioactive compound content. However, this fresh vegetable faces challenges related to its perishability and short shelf life. This study explores the effect of five drying methods, namely vacuum drying (VD), convective drying (CD), infrared drying (IRD), low-temperature vacuum drying (LTVD) and vacuum freeze-drying (VFD), on the bioactive compounds and health-promoting properties of cauliflower. Analyses of amino acids, hydroxycinnamic acid and its derivatives, glucosinolates, and isothiocyanates, as well as evaluations of their anti-inflammatory, antiproliferative, and neuroprotective properties, were conducted based on these five drying methods. The results revealed that samples treated with VFD and IRD had a higher content of amino acids involved in GSL anabolism. Moreover, VFD samples retained hydroxycinnamic acid derivatives and glucosinolates to a greater extent than other methods. Nonetheless, the CD and VD samples exhibited higher antiproliferative and neuroprotective effects, which were correlated with their high sulforaphane content. Overall, considering the retention of most bioactive compounds from cauliflower and the topical inflammation amelioration induced in mice, VFD emerges as a more satisfactory option.

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Parkinson's disease (PD) is the second most common late-onset neurodegenerative disease and the predominant cause of movement problems. PD is characterized by motor control impairment by extensive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). This selective dopaminergic neuronal loss is in part triggered by intracellular protein inclusions called Lewy bodies, which are composed mainly of misfolded alpha-synuclein (α-syn) protein. We previously reported insulin-like growth factor 2 (IGF2) as a key protein downregulated in PD patients. Here we demonstrated that IGF2 treatment or IGF2 overexpression reduced the α-syn aggregates and their toxicity by IGF2 receptor (IGF2R) activation in cellular PD models. Also, we observed IGF2 and its interaction with IGF2R enhance the α-syn secretion. To determine the possible IGF2 neuroprotective effect in vivo we used a gene therapy approach in an idiopathic PD model based on α-syn preformed fibrils intracerebral injection. IGF2 gene therapy revealed a significantly preventing of motor impairment in idiopathic PD model. Moreover, IGF2 expression prevents dopaminergic neuronal loss in the SN together with a decrease in α-syn accumulation (phospho-α-syn levels) in the striatum and SN brain region. Furthermore, the IGF2 neuroprotective effect was associated with the prevention of synaptic spines loss in dopaminergic neurons in vivo. The possible mechanism of IGF2 in cell survival effect could be associated with the decrease of the intracellular accumulation of α-syn and the improvement of dopaminergic synaptic function. Our results identify to IGF2 as a relevant factor for the prevention of α-syn toxicity in both in vitro and preclinical PD models.

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Parkinson's disease (PD) is the second most common neurodegenerative disorder, and no efficient therapy able to cure or slow down PD is available. In this study, dehydrated red cabbage was evaluated as a novel source of bio-compounds with neuroprotective capacity. Convective drying was carried out at different temperatures. Total phenolics (TPC), flavonoids (TFC), anthocyanins (TAC), and glucosinolates (TGC) were determined using spectrophotometry, amino acid profile by LC-DAD and fatty acid profile by GC-FID. Phenolic characterization was determined by liquid chromatography-high-resolution mass spectrometry. Cytotoxicity and neuroprotection assays were evaluated in SH-SY5Y human cells, observing the effect on preformed fibrils of α-synuclein. Drying kinetic confirmed a shorter processing time with temperature increase. A high concentration of bio-compounds was observed, especially at 90 °C, with TPC = 1544.04 ± 11.4 mg GAE/100 g, TFC = 690.87 ± 4.0 mg QE/100 g and TGC = 5244.9 ± 260.2 µmol SngE/100 g. TAC degraded with temperature. Glutamic acid and arginine were predominant. Fatty acid profiles were relatively stable and were found to be mostly C18:3n3. The neochlorogenic acid was predominant. The extracts had no cytotoxicity and showed a neuroprotective effect at 24 h testing, which can extend in some cases to 48 h. The present findings underpin the use of red cabbage as a functional food ingredient.

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Huntington's disease (HD) is a disorder caused by an abnormal expansion of trinucleotide CAG repeats within the huntingtin (Htt) gene. Under normal conditions, the CREB Binding Protein interacts with CREB elements and acetylates Lysine 27 of Histone 3 to direct the expression of several genes. However, mutant Htt causes depletion of CBP, which in turn induces altered histone acetylation patterns and transcriptional deregulation. Here, we have studied a differential expression analysis and H3K27ac variation in 4- and 6-week-old R6/2 mice as a model of juvenile HD. The analysis of differential gene expression and acetylation levels were integrated into Gene Regulatory Networks revealing key regulators involved in the altered transcription cascade. Our results show changes in acetylation and gene expression levels that are related to impaired neuronal development, and key regulators clearly defined in 6-week-old mice are proposed to drive the downstream regulatory cascade in HD. Here, we describe the first approach to determine the relationship among epigenetic changes in the early stages of HD. We determined the existence of changes in pre-symptomatic stages of HD as a starting point for early onset indicators of the progression of this disease.

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In this study, vacuum drying (VD) was employed as an approach to protect the bioactive components of and produce dried broccoli powders with a high biological activity. To achieve these goals, the effects of temperature (at the five levels of 50, 60, 70, 80 and 90 °C) and constant vacuum pressure (10 kPa) were evaluated. The results show that, with the increasing temperature, the drying time decreased. Based on the statistical tests, the Brunauer-Emmett-Teller (BET) model was found to fit well to sorption isotherms, whereas the Midilli and Kucuk model fit well to the drying kinetics. VD has a significant impact on several proximate composition values. As compared with the fresh sample, VD significantly reduced the total phenol, flavonoid and glucosinolate contents. However, it was shown that VD at higher temperatures (80 and 90 °C) contributed to a better antioxidant potential of broccoli powder. In contrast, 50 °C led to a better antimicrobial and neuroprotective effects, presumably due to the formation of isothiocyanate (ITC). Overall, this study demonstrates that VD is a promising technique for the development of extracts from broccoli powders that could be used as natural preservatives or as a neuroprotective agent.

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Alzheimer's disease (AD) is the most prevalent age-associated neurodegenerative disease. A decrease in autophagy during aging contributes to brain disorders by accumulating potentially toxic substrates in neurons. Rubicon is a well-established inhibitor of autophagy in all cells. However, Rubicon participates in different pathways depending on cell type, and little information is currently available on neuronal Rubicon's role in the AD context. Here, we investigated the cell-specific expression of Rubicon in postmortem brain samples from AD patients and 5xFAD mice and its impact on amyloid ß burden in vivo and neuroblastoma cells. Further, we assessed Rubicon levels in human-induced pluripotent stem cells (hiPSCs), derived from early-to-moderate AD and in postmortem samples from severe AD patients. We found increased Rubicon levels in AD-hiPSCs and postmortem samples and a notable Rubicon localization in neurons. In AD transgenic mice lacking Rubicon, we observed intensified amyloid ß burden in the hippocampus and decreased Pacer and p62 levels. In APP-expressing neuroblastoma cells, increased APP/amyloid ß secretion in the medium was found when Rubicon was absent, which was not observed in cells depleted of Atg5, essential for autophagy, or Rab27a, required for exosome secretion. Our results propose an uncharacterized role of Rubicon on APP/amyloid ß homeostasis, in which neuronal Rubicon is a repressor of APP/amyloid ß secretion, defining a new way to target AD and other similar diseases therapeutically.

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Perilesional edema, associated or not with neurological manifestations, is a well-characterized finding in cases of calcified neurocysticercosis. There are no previous reports of HIV-related calcified toxoplasmosis that mimics this presentation of neurocysticercosis. We report on five patients, four of them with new-onset neurological manifestations, who showed brain calcifications associated with perilesional edema. All cases had a history of HIV-related toxoplasmosis and current virological and immunological control of HIV infection. Similar to neurocysticercosis, brain calcified toxoplasmosis may cause perilesional edema and symptoms in people living with HIV/AIDS.

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Parkinson's disease (PD) is caused by the degeneration of dopaminergic neurons due to an accumulation of intraneuronal abnormal alpha-synuclein (α-syn) protein aggregates. It has been reported that the levels of exosomal α-syn of neuronal origin in plasma correlate significantly with motor dysfunction, highlighting the exosomes containing α-syn as a potential biomarker of PD. In addition, it has been found that the selective autophagy-lysosomal pathway (ALP) contributes to the secretion of misfolded proteins involved in neurodegenerative diseases. In this review, we describe the evidence that supports the relationship between the ALP and α-syn exosomal secretion on the PD progression and its implications in the diagnosis and progression of this pathology.

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Insulin-like growth factor 2 (IGF2) and autophagy-related genes have been proposed as biomolecules of interest related to idiopathic Parkinson's disease (PD). The objective of this study was to determine the IGF2 and IGF1 levels in plasma and peripheral blood mononuclear cells (PBMCs) from patients with moderately advanced PD and explore the potential correlation with autophagy-related genes in the same blood samples. IGF1 and IGF2 levels in patients' plasma were measured by ELISA, and the IGF2 expression levels were determined by real-time PCR and Western blot in PBMCs. The expression of autophagy-related genes was evaluated by real-time PCR. The results show a significant decrease in IGF2 plasma levels in PD patients compared with a healthy control group. We also report a dramatic decrease in IGF2 mRNA and protein levels in PBMCs from PD patients. In addition, we observed a downregulation of key components of the initial stages of the autophagy process. Although IGF2 levels were not directly correlated with disease severity, we found a correlation between its levels and autophagy gene profile expression in a sex-dependent pattern from the same samples. To further explore this correlation, we treated mice macrophages cell culture with α-synuclein and IGF2. While α-synuclein treatment decreased levels Atg5, IGF2 treatment reverted these effects, increasing Atg5 and Beclin1 levels. Our results suggest a relationship between IGF2 levels and the autophagy process in PD and their potential application as multi-biomarkers to determine PD patients' stages of the disease.

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Parkinson's disease is the second most common neurodegenerative disorder. Although it is clear that dopaminergic neurons degenerate, the underlying molecular mechanisms are still unknown, and thus, successful treatment is still elusive. One pro-apoptotic pathway associated with several neurodegenerative diseases is the tyrosine kinase c-Abl and its target p73. Here, we evaluated the contribution of c-Abl and p73 in the degeneration of dopaminergic neurons induced by the neurotoxin 6-hydroxydopamine as a model for Parkinson's disease. First, we found that in SH-SY5Y cells treated with 6-hydroxydopamine, c-Abl and p73 phosphorylation levels were up-regulated. Also, we found that the pro-apoptotic p73 isoform TAp73 was up-regulated. Then, to evaluate whether c-Abl tyrosine kinase activity is necessary for 6-hydroxydopamine-induced apoptosis, we co-treated SH-SY5Y cells with 6-hydroxydopamine and Imatinib, a c-Abl specific inhibitor, observing that Imatinib prevented p73 phosphorylation, TAp73 up-regulation, and protected SH-SY5Y cells treated with 6-hydroxydopamine from apoptosis. Interestingly, this observation was confirmed in the c-Abl conditional null mice, where 6-hydroxydopamine stereotaxic injections induced a lesser reduction of dopaminergic neurons than in the wild-type mice significantly. Finally, we found that the intraperitoneal administration of Imatinib prevented the death of dopaminergic neurons induced by injecting 6-hydroxydopamine stereotaxically in the mice striatum. Thus, our findings support the idea that the c-Abl/p73 pathway is involved in 6-hydroxydopamine degeneration and suggest that inhibition of its kinase activity might be used as a therapeutical drug in Parkinson's disease.

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Neurological motor disorders (NMDs) such as Parkinson's disease and Huntington's disease are characterized by the accumulation and aggregation of misfolded proteins that trigger cell death of specific neuronal populations in the central nervous system. Differential neuronal loss initiates the impaired motor control and cognitive function in the affected patients. Although major advances have been carried out to understand the molecular basis of these diseases, to date there are no treatments that can prevent, cure, or significantly delay the progression of the disease. In this context, strategies such as gene editing, cellular therapy, among others, have gained attention as they effectively reduce the load of toxic protein aggregates in different models of neurodegeneration. Nevertheless, these strategies are expensive and difficult to deliver into the patients' nervous system. Thus, small molecules and natural products that reduce protein aggregation levels are highly sought after. Numerous drug discovery efforts have analyzed large libraries of synthetic compounds for the treatment of different NMDs, with a few candidates reaching clinical trials. Moreover, the recognition of new druggable targets for NMDs has allowed the discovery of new small molecules that have demonstrated their efficacy in pre-clinical studies. It is also important to recognize the contribution of natural products to the discovery of new candidates that can prevent or cure NMDs. Additionally, the repurposing of drugs for the treatment of NMDs has gained huge attention as they have already been through clinical trials confirming their safety in humans, which can accelerate the development of new treatment. In this review, we will focus on the new advances in the discovery of small molecules for the treatment of Parkinson's and Huntington's disease. We will begin by discussing the available pharmacological treatments to modulate the progression of neurodegeneration and to alleviate the motor symptoms in these diseases. Then, we will analyze those small molecules that have reached or are currently under clinical trials, including natural products and repurposed drugs.

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Accumulation of misfolded proteins in the brain is a common hallmark of most age-related neurodegenerative diseases. Previous studies from our group identified the presence of anti-inflammatory and antioxidant compounds in leaves derived from the Chilean berry Ugni molinae (murtilla), in addition to show a potent anti-aggregation activity in models of Alzheimer´s disease. However, possible beneficial effects of berry extracts of murtilla was not investigated. Here we evaluated the efficacy of fruit extracts from different genotypes of Chilean-native U. molinae on reducing protein aggregation using cellular models of Huntington´s disease and assess the correlation with their chemical composition. Berry extraction was performed by exhaustive maceration with increasing-polarity solvents. An unbiased automatic microscopy platform was used for cytotoxicity and protein aggregation studies in HEK293 cells using polyglutamine-EGFP fusion proteins, followed by secondary validation using biochemical assays. Phenolic-rich extracts from murtilla berries of the 19-1 genotype (ETE 19-1) significantly reduced polyglutamine peptide aggregation levels, correlating with the modulation in the expression levels of autophagy-related proteins. Using LC-MS and molecular network analysis we correlated the presence of flavonoids, phenolic acids, and ellagitannins with the protective effects of ETE 19-1 effects on protein aggregation. Overall, our results indicate the presence of bioactive components in ethanolic extracts from U. molinae berries that reduce the load of protein aggregates in living cells.

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Objetivo: Los desórdenes de mucosa bucal potencialmente malignos pueden presentar áreas displásicas. En estos casos, la biopsia es un procedimiento imprescindible para un correcto diagnóstico. La inspección visual y la palpación, como método de selección del área de biopsia, ofrecen sensibilidad y especificidad adecuadas pero mejorables. El objetivo de este artículo es presentar una serie de casos clínicos en los que se describen el empleo y la interpretación de la tinción vital con azul de toluidina como método complementario para contribuir a una mejor elección del área de biopsia. Casos clínicos: Se trata de siete casos de lesiones con sospecha de displasia epitelial en mucosa bucal. En cada uno se detalla la correlación de las áreas teñidas con las manifestaciones clínicas y con el diagnóstico de displasia. Además, se muestran patrones de tinción considerados falsos positivos. En la interpretación de la tinción positiva, se tuvieron en cuenta el aspecto superficial y el color de la lesión teñida. El empleo combinado de inspección, palpación y tinción vital podría constituir un procedimiento integral de utilidad para obtener mayor precisión en la determinación del sitio de biopsia en comparación con los mismos procedimientos aplicados de manera individual. En la interpretación de la tinción positiva con azul de toluidina deberían considerarse el aspecto superficial y el color de la lesión teñida (AU)

Aim: Potentially Malignant Disorders in the oral cavity can present dysplastic areas. In these cases, the biopsy is an essential procedure for a correct diagnosis. Visual inspection and palpation, are adequate methods to select the area for the biopsy, however there is margin for improvement. The objective of this article is to present a series of clinical cases in which the use and interpretation of vital staining with Toluidine Blue is described as a complementary method to contribute to a better choice of the biopsy area. Clinical cases: Seven clinical cases that presented lesions with suspected epithelial dysplasia in the oral mucosa were presented. The correlation of the stained areas with the clinical manifestations and with the diagnosis of dysplasia is detailed in each case. Staining patterns considered false positives are also shown. In the interpretation of the positive staining, the superficial appearance and color of the stained lesion were considered. The combined use of inspection, palpation and vital staining could constitute a useful comprehensive procedure to obtain greater precision in determining the biopsy site in relation to the same procedures applied individually. In the interpretation of the positive staining with Toluidine Blue, the superficial appearance and color of the stained lesion should be considered (AU)

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INTRODUCTION: Semantic dementia (SD) is characterized by fluent speech, anomia, and loss of word and object knowledge with varying degrees of right and left anterior-medial temporal lobe hypometabolism on [18F] fluorodeoxyglucose (FDG)-PET. We assessed neurobehavioral features in SD patients across 3 FDG-PET-defined metabolic patterns and investigated progression over time. METHODS: Thirty-four patients with SD who completed FDG-PET were classified into a left- and right-dominant group based on the degree of hypometabolism in each temporal lobe. The left-dominant group was further subdivided depending on whether hypometabolism in the right temporal lobe was more or less than 2 standard deviations from controls (left+ group). Neurobehavioral characteristics determined using the Neuropsychiatric Inventory Questionnaire (NPI-Q) were compared across groups. Progression of NPI-Q scores and FDG-PET hypometabolism was assessed in 14 patients with longitudinal follow-up. RESULTS: The right-dominant group performed worse on the NPI-Q and had a greater frequency of abnormal behaviors and more severe disinhibition compared to the left-dominant group. Performance on the NPI-Q and severity of disinhibition correlated with right medial and lateral, but not left, temporal lobe hypometabolism. Severity of abnormal behaviors worsened over time in most left-dominant and left+ patients but appeared to improve in the 2 right-dominant patients with longitudinal follow-up. All groups showed progressive worsening of metabolism in both temporal lobes over time, with hypometabolism spreading from anteromedial to posterior temporal regions. However, the degree of temporal lobe asymmetry remained relatively constant over time. CONCLUSION: In SD, neurobehavioral features, especially disinhibition, are associated with right medial and lateral temporal lobe hypometabolism and commonly develop over time even in patients that present with left-dominant patterns of hypometabolism.

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Movement disorders are neurological conditions in which patients manifest a diverse range of movement impairments. Distinct structures within the basal ganglia of the brain, an area involved in movement regulation, are differentially affected for every disease. Among the most studied movement disorder conditions are Parkinson's (PD) and Huntington's disease (HD), in which the deregulation of the movement circuitry due to the loss of specific neuronal populations in basal ganglia is the underlying cause of motor symptoms. These symptoms are due to the loss principally of dopaminergic neurons of the substantia nigra (SN) par compacta and the GABAergic neurons of the striatum in PD and HD, respectively. Although these diseases were described in the 19th century, no effective treatment can slow down, reverse, or stop disease progression. Available pharmacological therapies have been focused on preventing or alleviating motor symptoms to improve the quality of life of patients, but these drugs are not able to mitigate the progressive neurodegeneration. Currently, considerable therapeutic advances have been achieved seeking a more efficacious and durable therapeutic effect. Here, we will focus on the new advances of several therapeutic approaches for PD and HD, starting with the available pharmacological treatments to alleviate the motor symptoms in both diseases. Then, we describe therapeutic strategies that aim to restore specific neuronal populations or their activity. Among the discussed strategies, the use of Neurotrophic factors (NTFs) and genetic approaches to prevent the neuronal loss in these diseases will be described. We will highlight strategies that have been evaluated in both Parkinson's and Huntington's patients, and also the ones with strong preclinical evidence. These current therapeutic techniques represent the most promising tools for the safe treatment of both diseases, specifically those aimed to avoid neuronal loss during disease progression.

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Impaired neuronal proteostasis is a salient feature of many neurodegenerative diseases, highlighting alterations in the function of the endoplasmic reticulum (ER). We previously reported that targeting the transcription factor XBP1, a key mediator of the ER stress response, delays disease progression and reduces protein aggregation in various models of neurodegeneration. To identify disease modifier genes that may explain the neuroprotective effects of XBP1 deficiency, we performed gene expression profiling of brain cortex and striatum of these animals and uncovered insulin-like growth factor 2 (Igf2) as the major upregulated gene. Here, we studied the impact of IGF2 signaling on protein aggregation in models of Huntington's disease (HD) as proof of concept. Cell culture studies revealed that IGF2 treatment decreases the load of intracellular aggregates of mutant huntingtin and a polyglutamine peptide. These results were validated using induced pluripotent stem cells (iPSC)-derived medium spiny neurons from HD patients and spinocerebellar ataxia cases. The reduction in the levels of mutant huntingtin was associated with a decrease in the half-life of the intracellular protein. The decrease in the levels of abnormal protein aggregation triggered by IGF2 was independent of the activity of autophagy and the proteasome pathways, the two main routes for mutant huntingtin clearance. Conversely, IGF2 signaling enhanced the secretion of soluble mutant huntingtin species through exosomes and microvesicles involving changes in actin dynamics. Administration of IGF2 into the brain of HD mice using gene therapy led to a significant decrease in the levels of mutant huntingtin in three different animal models. Moreover, analysis of human postmortem brain tissue and blood samples from HD patients showed a reduction in IGF2 level. This study identifies IGF2 as a relevant factor deregulated in HD, operating as a disease modifier that buffers the accumulation of abnormal protein species.

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