Candelilla Wax Extracted by Traditional Method and an Ecofriendly Process: Assessment of Its Chemical, Structural and Thermal Properties.

A comparative study was carried out on the chemical, structural and thermal properties of candelilla wax from four wax-producing communities in Mexico, which was obtained by two extraction processes, the conventional one using sulfuric acid (SA) and an eco-friendly alternative process using citric acid (CA) as the extracting agent. The waxes were analyzed by basic chemistry (acidity, saponification, ester indexes, and others), color, Fourier transform infrared spectroscopy (FTIR), Raman micro-spectroscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and hardness and brittleness measurements. The waxes obtained by the environmentally friendly process showed differences in their physicochemical properties when compared to waxes from the conventional process. In addition, they showed some improvements, such as lighter shades and harder waxes, suggesting that the new environmentally friendly process is a viable option.

Neurovascular dysfunction and vascular amyloid accumulation as early events in Alzheimer's disease.

Alzheimer's disease (AD) is clinically characterized by a progressive loss of cognitive functions and short-term memory. AD patients present two distinctive neuropathological lesions: neuritic plaques and neurofibrillary tangles (NFTs), constituted of beta-amyloid peptide (Aß) and phosphorylated and truncated tau proteins. Aß deposits around cerebral blood vessels (cerebral amyloid angiopathy, CAA) is a major contributor to vascular dysfunction in AD. Vascular amyloid deposits could be early events in AD due to dysfunction in the neurovascular unit (NVU) and the blood-brain barrier (BBB), deterioration of the gliovascular unit, and/or decrease of cerebral blood flow (CBF). These pathological events can lead to decreased Aß clearance, facilitate a neuroinflammatory environment as well as synaptic dysfunction and, finally, lead to neurodegeneration. Here, we review the histopathological AD hallmarks and discuss the two-hit vascular hypothesis of AD, emphasizing the role of neurovascular dysfunction as an early factor that favors vascular Aß aggregation and neurodegeneration. Addtionally, we emphasize that pericyte degeneration is a key and early element in AD that can trigger amyloid vascular accumulation and NVU/BBB dysfunction. Further research is required to better understand the early pathophysiological mechanisms associated with NVU alteration and CAA to generate early biomarkers and timely treatments for AD.

Current Status and Challenges of Stem Cell Treatment for Alzheimer's Disease.

Neurodegenerative diseases called tauopathies, such as Alzheimer's disease (AD), frontotemporal dementia, progressive supranuclear palsy, and Parkinson's disease, among others, are characterized by the pathological processing and accumulation of tau protein. AD is the most prevalent neurodegenerative disease and is characterized by two lesions: neurofibrillary tangles (NFTs) and neuritic plaques. The presence of NFTs in the hippocampus and neocortex in early and advanced stages, respectively, correlates with the patient's cognitive deterioration. So far, no drugs can prevent, decrease, or limit neuronal death due to abnormal pathological tau accumulation. Among potential non-pharmacological treatments, physical exercise has been shown to stimulate the development of stem cells (SCs) and may be useful in early stages. However, this does not prevent neuronal death from the massive accumulation of NFTs. In recent years, SCs therapies have emerged as a promising tool to repopulate areas involved in cognition in neurodegenerative diseases. Unfortunately, protocols for SCs therapy are still being developed and the mechanism of action of such therapy remains unclear. In this review, we show the advances and limitations of SCs therapy. Finally, we provide a critical analysis of its clinical use for AD.

Insoluble Vascular Amyloid Deposits Trigger Disruption of the Neurovascular Unit in Alzheimer's Disease Brains.

Alzheimer's disease (AD) is a neurodegenerative disease, characterized histopathologically by intra-neuronal tau-related lesions and by the accumulation of amyloid ß-peptide (Aß) in the brain parenchyma and around cerebral blood vessels. According to the vascular hypothesis of AD, an alteration in the neurovascular unit (NVU) could lead to Aß vascular accumulation and promote neuronal dysfunction, accelerating neurodegeneration and dementia. To date, the effects of insoluble vascular Aß deposits on the NVU and the blood-brain barrier (BBB) are unknown. In this study, we analyze different Aß species and their association with the cells that make up the NVU. We evaluated post-mortem AD brain tissue. Multiple immunofluorescence assays were performed against different species of Aß and the main elements that constitute the NVU. Our results showed that there are insoluble vascular deposits of both full-length and truncated Aß species. Besides, insoluble aggregates are associated with a decrease in the phenotype of the cellular components that constitute the NVU and with BBB disruption. This approach could help identify new therapeutic targets against key molecules and receptors in the NVU that can prevent the accumulation of vascular fibrillar Aß in AD.

Tau Protein Phosphorylated at Threonine-231 is Expressed Abundantly in the Cerebellum in Prion Encephalopathies.

BACKGROUND: Transmissible spongiform encephalopathies (TSEs) are rare neurodegenerative disorders that affect animals and humans. Bovine spongiform encephalopathy (BSE) in cattle, and Creutzfeld-Jakob Disease (CJD) in humans belong to this group. The causative agent of TSEs is called "prion", which corresponds to a pathological form (PrPSc) of a normal cellular protein (PrPC) expressed in nerve cells. PrPSc is resistant to degradation and can induce abnormal folding of PrPC, and TSEs are characterized by extensive spongiosis and gliosis and the presence of PrPSc amyloid plaques. CJD presents initially with clinical symptoms similar to Alzheimer's disease (AD). In AD, tau aggregates and amyloid-ß protein plaques are associated with memory loss and cognitive impairment in patients. OBJECTIVE: In this work, we study the role of tau and its relationship with PrPSc plaques in CJD. METHODS: Multiple immunostainings with specific antibodies were carried out and analyzed by confocal microscopy. RESULTS: We found increased expression of the glial fibrillary acidic protein (GFAP) and matrix metalloproteinase (MMP-9), and an exacerbated apoptosis in the granular layer in cases with prion disease. In these cases, tau protein phosphorylated at Thr-231 was overexpressed in the axons and dendrites of Purkinje cells and the extensions of parallel fibers in the cerebellum. CONCLUSION: We conclude that phosphorylation of tau may be a response to a toxic and inflammatory environment generated by the pathological form of prion.

Molecular Processing of Tau Protein in Progressive Supranuclear Palsy: Neuronal and Glial Degeneration.

BACKGROUND: Alzheimer's disease (AD) and progressive supranuclear palsy (PSP) are examples of neurodegenerative diseases, characterized by abnormal tau inclusions, that are called tauopathies. AD is characterized by highly insoluble paired helical filaments (PHFs) composed of tau with abnormal post-translational modifications. PSP is a neurodegenerative disease with pathological and clinical heterogeneity. There are six tau isoforms expressed in the adult human brain, with repeated microtubule-binding domains of three (3R) or four (4R) repeats. In AD, the 4R:3R ratio is 1:1. In PSP, the 4R isoform predominates. The lesions in PSP brains contain phosphorylated tau aggregates in both neurons and glial cells. OBJECTIVE: Our objective was to evaluate and compare the processing of pathological tau in PSP and AD. METHODS: Double and triple immunofluorescent labeling with antibodies to specific post-translational tau modifications (phosphorylation, truncation, and conformational changes) and thiazin red (TR) staining were carried out and analyzed by confocal microscopy. RESULTS: Our results showed that PSP was characterized by phosphorylated tau in neurofibrillary tangles (NFTs) and glial cells. Tau truncated at either Glu391 or Asp421 was not observed. Extracellular NFTs (eNFTs) and glial cells in PSP exhibited a strong affinity for TR in the absence of intact or phosphorylated tau. CONCLUSION: Phosphorylated tau was as abundant in PSP as in AD. The development of eNFTs from both glial cells and neuronal bodies suggests that truncated tau species, different from those observed in AD, could be present in PSP. Additional studies on truncated tau within PSP lesions could improve our understanding of the pathological processing of tau and help identify a discriminatory biomarker for AD and PSP.

PHF-Core Tau as the Potential Initiating Event for Tau Pathology in Alzheimer's Disease.

Worldwide, around 50 million people have dementia. Alzheimer's disease (AD) is the most common type of dementia and one of the major causes of disability and dependency among the elderly worldwide. Clinically, AD is characterized by impaired memory accompanied by other deficiencies in the cognitive domain. Neuritic plaques (NPs) and neurofibrillary tangles (NFTs) are histopathological lesions that define brains with AD. NFTs consist of abundant intracellular paired helical filaments (PHFs) whose main constituent is tau protein. Tau undergoes posttranslational changes including hyperphosphorylation and truncation, both of which favor conformational changes in the protein. The sequential pathological processing of tau is illustrated with the following specific markers: pT231, TG3, AT8, AT100, and Alz50. Two proteolysis sites for tau have been described-truncation at glutamate 391 and at aspartate 421-and which can be demonstrated by reactivity with the antibodies 423 and TauC-3, respectively. In this review, we describe the molecular changes in tau protein as pre-NFTs progress to extracellular NFTs and during which the formation of a minimal nucleus of the filament, as the PHF core, occurs. We also analyzed the PHF core as the initiator of PHFs and tau phosphorylation as a protective neuronal mechanism against the assembly of the PHF core.

National Dementia BioBank: A Strategy for the Diagnosis and Study of Neurodegenerative Diseases in México.

We recently developed the National Dementia Biobank in México (BioBanco Nacional de Demencias, BND) as a unit for diagnosis, research, and tissue transfer for research purposes. BND is associated with the Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de Mexico (UNAM), Mexico. The donation of fluids, brain, and other organs of deceased donors is crucial for understanding the underlying mechanisms of neurodegenerative diseases and for the development of successful treatment. Our laboratory research focuses on 1) analysis of the molecular processing of the proteins involved in those neurodegenerative diseases termed tauopathies and 2) the search for biomarkers for the non-invasive and early diagnosis of Alzheimer's disease.

Milk intake and IGF-1 rs6214 polymorphism as protective factors to obesity.

Mexico ranks 2nd in adult obesity and 4th in milk intake worldwide. Low levels of IGF-1 have been related to obesity and can be reverted by milk intake. The rs6214 polymorphism has been associated with an increase in the expression of IGF-1. Therefore, the aim of the study was to evaluate the association between both, rs6214 polymorphism and milk intake, and obesity. We analysed 99 adult volunteers, with and without a history of milk intake, for the presence of this polymorphism through qPCR and body composition by electro-bioimpedance. Univariate logistic regression analyses showed that TT genotype is inversely associated with obesity and body fat mass. Besides, milk intake is also related to low obesity, body fat mass and visceral fat, and high percentage of lean mass. Multivariate logistic regression analyses confirm the univariate relationships, showing a clear inverted association between TT genotype, milk intake and obesity.

Phospho-Tau Protein Expression in the Cell Cycle of SH-SY5Y Neuroblastoma Cells: A Morphological Study.

It has been reported that the main function of tau protein is to stabilize microtubules and promote the movement of organelles through the axon in neurons. In Alzheimer's disease, tau protein is the major constituent of the paired helical filament, and it undergoes post-translational modifications including hyperphosphorylation and truncation. Whether other functions of tau protein are involved in Alzheimer's disease is less clear. We used SH-SY5Y human neuroblastoma cells as an in vitro model to further study the functions of tau protein. We detected phosphorylated tau protein as small dense dots in the cell nucleus, which strongly colocalize with intranuclear speckle structures that were also labelled with an antibody to SC35, a protein involved in nuclear RNA splicing. We have shown further that tau protein, phosphorylated at the sites recognized by pT231, TG-3, and AD2 antibodies, is closely associated with cell division. Different functions may be characteristic of phosphorylation at specific sites. Our findings suggest that the presence of tau protein is involved in separation of sister chromatids in anaphase, and that tau protein also participates in maintaining the integrity of the DNA (pT231, prophase) and chromosomes during cell division (TG-3).

Performance of a biofilter system with agave fiber filter media for municipal wastewater treatment.

Agave plants grow in semi-arid regions and are used for mescal production. However, agave fiber by-products are considered waste materials. Thus, we tested agave fiber as a filter media and biofilm material carrier for removing pollutants from municipal wastewater. Three laboratory-scale biofiltration reactors were used in two trials with five hydraulic loading rates (HLRs = 0.27, 0.54, 0.80, 1.07 and 1.34 m(3) m(-2) d(-1)). One series was conducted using mechanical aeration (0.62 m(3) m(-2) h(-1)). To prevent compaction, decreasing pressure and clogging of the filter media, 4, 8 and 12 internal divisions were evaluated in the biofilter column. After 17 months of continuous operation at an HLR of 0.80 m(3) m(-2) d(-1), the removal efficiencies of the aerated biofilters were 92.0% biochemical oxygen demand, 79.7% chemical oxygen demand, 98.0% helminth eggs, 99.9% fecal coliforms and 91.9% total suspended solids. Statistical analysis showed that the chosen operational parameters significantly influenced the removal efficiencies of the biofilters. The effluent quality obtained under these conditions complied with the Mexican and US EPA standards for agricultural irrigation and green spaces, except for coliforms, which is why the effluents must be disinfected. Thus, agave fiber is a favorable choice for use as a packing material in biofiltration processes.

Biochemical differences in ethnic groups in Durango, Mexico.

OBJECTIVE: The aim of this study was to assess biochemical differences between Tepehuano indigenous people, and Mennonite and Mestizo populations of Durango, Mexico. METHODS: Our study involved 334 volunteers aged 15 to 80 years; 132 Mennonite and 130 Mestizo individuals from Nuevo Ideal Municipality and 72 Tepehuano indigenous people from Mezquital Durango were evaluated. A clinical history and fast determination of aspartate aminotransferase (AST), alanine aminotransferase (ALT), uric acid, urea and creatinine were performed on each studied case. RESULTS: Statistically significant differences between the three studied groups were found for age, weight and height (P < .05), with higher values observed in men. The highest plasma urea levels were found in Mennonite compared to Mestizo people, followed by the Tepehuano indigenous. Higher biochemical parameters were found in men (vs women) in the studied groups. The percentage of individuals with abnormal levels for AST, ALT and uric acid were higher in Tepehuano indigenous people than in Mestizo, whereas the urea and creatinine percentages were higher in Mestizo people. CONCLUSION: The differences found on biochemical tests, could be explained by differences in lifestyle such as diet and sanitary habits.

HPLC method for quantification of oxidative stress by salicilate hydroxylation in human plasma.

The aim of the present study was to modify and validate a high-performance liquid chromatographic (HPLC) method for determining 2,3 and 2,5 dihydroxybenzoic acid (2,3-DHBA and 2,5-DHBA) from salicylic acid in human plasma. The mobile phase was a mixture of sodium acetate/citrate (pH 2.5) 30 mM-methanol (93:7, v/v). The injection volume was 10 muL. Retention time for 2,5-DHBA, and 2,3-DHBA was 4.5 +/- 0.10 and 5.8 +/- 0.15 min, respectively. The detection and quantification limits were 10 and 40 nM for 2,3-DHBA and 8 and 20 nM for 2,5-DHBA. Linearity was evaluated in the range of 40-1600 nM for both metabolites. Inter- and intra-analysis variation coefficient was below 10%. Good recoveries of more than 99% were obtained for both metabolites using this method.