Identification of Vascular Genes Differentially Expressed in the Brain of Patients with Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) plays a prominent role as the most common form of dementia. Moreover, the traditional mechanism of AD does not explain the microvascular damage observed in about 25-30 years between the onset of AD, which results in late application treatment that inhibits or delays neurodegeneration. OBJECTIVE: Our objective was to identify differentially expressed genes in human brain samples associated with vascular disruption in AD. METHODS: We analyzed 1633 post-mortem brain samples in the GEO to database and, after applying clinical and bioinformatic exclusion criteria, worked with 581 prefrontal and frontal samples. All datasets were analyzed using GEO2R from NCBI. We identified common genes using the Venny tool, and their metabolic relevance associated with AD and the vascular system was analyzed using MetaboAnalyst tools. RESULTS: Our bioinformatic analysis identified PRKCB, MAP2K2, ADCY1, GNA11, GNAQ, PRKACB, KCNMB4, CALD1, and GNAS as potentially involved in AD pathogenesis. These genes are associated with signal transductions, cell death signaling, and cytoskeleton, suggesting potential modulation of cellular physiology, including endoplasmic reticulum and mitochondrial activity. CONCLUSION: This study generates hypotheses regarding the roles of novel genes over critical pathways relevant to AD and its relation with vascular dysfunction. These findings suggest potential new targets for further investigation into the pathogenesis of dementia and AD.

Association between universal health coverage and the disease burden of acute illness and injury at the global level.

BACKGROUND: This study examines the relationship between universal health coverage (UHC) and the burden of emergency diseases at a global level. METHODS: Data on Disability-Adjusted Life Years (DALYs) from emergency conditions were extracted from the Institute for Health Metrics and Evaluation (IHME) database for the years 2015 and 2019. Data on UHC, measured using two variables 1) coverage of essential health services and 2) proportion of the population spending more than 10% of household income on out-of-pocket health care expenditure, were extracted from the World Bank Database for years preceding our outcome of interest. A linear regression was used to analyze the association between UHC variables and DALYs for emergency diseases, controlling for other variables. RESULTS: A total of 132 countries were included. The median national coverage of essential health services index was 67.5/100, while the median national prevalence of catastrophic spending in the sample was 6.74% of households. There was a strong significant relationship between health service coverage and the burden of emergency diseases, with an 11.5-point reduction in DALYs of emergency medical diseases (95% CI -9.5, -14.8) for every point increase in the coverage of essential health services index. There was no statistically significant relationship between catastrophic expenditures and the burden of emergency diseases, which may be indicative of inelastic demand in seeking services for health emergencies. CONCLUSION: Increasing the coverage of essential health services, as measured by the essential health services index, is strongly correlated with a reduction in the burden of emergency conditions. In addition, data affirms that financial protection remains inadequate in many parts of the globe, with large numbers of households experiencing significant economic duress related to seeking healthcare. This evidence supports a strategy of strengthening UHC as a means of combating death and disability from health emergencies, as well as extending protection against impoverishment related to healthcare expenses.

Mechanistic characterization and inhibition of sphingomyelinase C over substituted Iron Schiff bases of chitosan adsorbed on glassy carbon electrode.

The medical treatment of laxoscelisms is based solely on supportive measures. Although equine antiserum for Sphingomyelinase C (SMASE) and D isomers are available, it is not used due to the risk of an anaphylactic reaction and its unproven efficacy. As potential enzyme inhibitors, derivatives of Iron chitosan complexes were studied (Shiff base having -R = -H, -Cl, -Br, -F, -OCH3, -CH3, -NO2). These chitosan complexes were chosen because they have revealed good results in medicine and catalysis due to their biodegradable characteristics and bioavailability. Besides considering that these complexes have not been studied in relation to this toxin. The mechanisms underlying the catalytic and catcher effects of Iron chitosan complexes were studied using electrochemistry, UV-Vis spectroscopy and microscopic assay at physiological pH. The electrochemical studies showed that one of seven Schiff bases of chitosan adsorbed on glassy carbon electrode was electrocatalytically active for the oxidation of sphingomyelinase at 1.27 V, and that allowed proposing a reaction scheme for SMASE oxidation by adsorbed Iron complexes. On the other hand, even though the spectroscopic studies indicated that there was no chemical bond formation between the complex and SMASE in solution, the microscopic studies showed that this complex proved to be a remarkable cellular protector in presence of the enzyme. In conclusion, Shiff base of chitosan with R = -CH3 was the only active complex in front of sphingomyelinase C, protecting red blood cells, according to our electrochemical and microscopic studies.

Structural studies of the exopolysaccharide produced by a submerged culture of entomopathogenic fungus Metarhizium anisopliae / Estudio estructural del exopolisacárido producido por un cultivo sumergido del hongo entomopatogénico Metarhizium anisopliae

The exopolysaccharide (EPS) separated from the entomopathogenic fungus Metarhizium anisopliae was determined by gel permeation chromatography to be homogeneous. The high-performance anion-exchange chromatography with pulsed-amperometric detection (HPAE-PAD) showed a content of monosaccharides D-galactosamine and D-fucose at a molar ratio of about 2:1. The results obtained from Fourier transform-infrared spectroscopy (FT-IR) and second derivative FT-IR spectrum confirmed the proposed structure.

El exopolisacárido (EPS) separado desde el hongo entomopatogénico Metarhizium anisopliae determinado por cromatografía de exclusión en gel ser homogéneo. La cromatografía iónica de alto rendimiento con detección de pulso amperométrico (HPAE-PAD) mostró un contenido de monosacáridos D-galactosamina y D-fucosa en una relación molar de alrededor de 2:1. Los resultados obtenidos desde la espectroscopía infrarroja con transformada de Fourier (FT-IR) y la segunda derivada del espectro FT-IR confirmaron la estructura propuesta.

Antibacterial activity of an oligosaccharide of native Paecilomyces sp. and its aminoglycosylated derivative.

This study reports the antibacterial activity of an oligosaccharide, prepared by partial acid hydrolysis of a native Paecilomyces sp. exopolysaccharide, and of its aminoglycosylated derivative, prepared by reductive alkylation of the oligosaccharide, against E. coli and S. aureus.

Solubility effects on antibacterial activity of chemically modified chitooligosaccharides of fungal origin / Efectos de la solubilidad sobre la actividad antibacteriana de quitooligosacáridos modificados químicamente de origen fúngico

Chitin and chitosan are a class of metabolites that occurring in some fungi species that are associated with commercial and medicinal plants, this is in Mucor sp. for example with an ample number of biological activities, being antibacterial and antifungal one of the most important. Into our program of search of biopesticides and natural compounds with biological activities, we have studying chitosan that was obtained from the culture medium of the fungus Mucor ruoxii. Chitooligosaccharides were prepared by partial acid hydrolysis of native chitosan and an aminoglycosylated derivative was obtained by reductive amination of the chitooligosaccaride. The solubilities of these compounds were measured at different pHs and its antibacterial activity against Escherichia coli (gram-negative) and Staphylococcus aureus (gram-positive). Chitosan and the derivatives tested exhibited a good antibacterial activity against S. aureus.

Quitina y quitosano son una clase de metabolitos que producen algunas especies de hongos que están asociados con plantas medicinales y comerciales, esto es por ejemplo en Mucor sp., con un amplio número de actividades biológicas, siendo la antibacteriana y antifúngica unas de las más importantes. En nuestro programa de investigación de biopesticidas y compuestos naturales, estamos estudiando quitosano obtenido de el medio de cultivo del hongo Mucor ruoxii. Quitooligosacáridos fueron preparados por hidrólisis parcial ácida de quitosano nativo y un derivado aminoglicosilado fue obtenido por aminación reductiva del quitooligosacárido. Las solubilidades de estos compuestos fueron medidas a diferentes pHs y su actividad antibacteriana frente a Escherichia coli (gram-negative) and Staphylococcus aureus (gram-positive). Quitosano y los derivados testeados exhiben una buena actividad antibacteriana frente a S. aureus.

Antibacterial activity of chitooligosaccharides.

The aim of this study was to investigate the antibacterial activity of chitooligosaccharide, prepared by partial acid hydrolysis of chitosan, and of an aminoglycosylated derivative, prepared by reductive alkylation of the chitooligosaccharide, against E. coli and S. aureus.

Biotransformation of indole derivatives by mycelial cultures.

Biotransformation of tryptophan to tryptamine and 3-methyl-indole by Psilocybe coprophila was performed. On the other hand, Aspergillus niger was able to transform tryptophan to 5-hydroxy-tryptophan. P. coprophila biotransformed 5-hydroxy-tryptophan to 5-hydroxytryptamine. These results prove once more that fungi are good tools to establish hydroxyindole derivatives.

Structural studies of native Paecilomyces sp. Exopolysaccharide.

A polysaccharide separated from Paecilomyces sp. was determined by gel permeation chromatography to be homogeneous. HPLC showed a monosaccharide containing D-glucose and D-fructose at a ratio of about 2:1. The results obtained from IR, 1H NMR, and 13C NMR analyses confirmed the proposed structure.

Production of exopolysaccharides by a submerged culture of an entomopathogenic fungus, Paecilomyces sp.

Exopolysaccharide basic was obtained from a submerged culture of a native Paecilomyces sp. strain isolated from Chilean soil.

Salmonella enterica serovar Typhi O:1,9,12 polysaccharide-protein conjugate as a diagnostic tool for typhoid fever.

Serologic tests play an important role in diagnosis of typhoid fever. In an effort to develop a more defined reagent for these tests, purified Salmonella enterica serovar Typhi (ST) O:1,9,12 polysaccharide was conjugated to human serum albumin (HSA), and the conjugate was purified chromatographically to yield a reagent with 2 moles ST O polysaccharide per mole HSA. In 40 patients with bacteriologically confirmed typhoid fever, significant dot immunobinding titers (> or =20,000) were present in 28 (70%) tested with 100 ng of ST O antigen-HSA (ST O-HSA) conjugate, in 38 (95%) tested with 100 ng of ST lipopolysaccharide, and in 16 (40%) tested with purified unconjugated ST O chains. In sera from 22 patients with other nontyphoid fevers, 2 (9.1%) had such reactivities with 100 ng of ST O-HSA, 1 (4.5%) had such reactivity with 100 ng of ST lipopolysaccharide (4.5%), and none reacted with 100 ng of unconjugated ST O chains. None of the 17 healthy-control sera reacted significantly with any of the ST reagents. None of the patient or control sera reacted with unconjugated HSA. The sensitivity of dot immunobinding for typhoid fever was 70% with 100 ng of ST O-HSA, somewhat lower than that with 100 ng of ST lipopolysaccharide (95%) but similar to that of the Widal H agglutination test with a > or =1/160 cutoff (74%). Specificities of these tests were 91%, 95%, and 86%, respectively. These preliminary results suggest that ST O polysaccharide-protein conjugates could provide a nontoxic, easily quality-controlled synthetic reagent for analysis of human immune responses to ST as well as for the development of new diagnostics and vaccines for typhoid fever.

Ni(II) complexes with Schiff bases derived from amino sugars.

It was found by 1H and 13C NMR spectroscopy that the Schiff base, 2-deoxy-2-(2-hydroxybenzaldimino)-D-glucopyranose exhibits enol-imine-keto-amine and anomeric equilibria in methanolic, and in dimethyl sulfoxide solutions. The reaction of the Schiff base with nickel acetate gave the bidentate, mononuclear Ni(II) complex that was characterized by spectroscopic methods and by cyclic voltammetry. The coordination of the Schiff base to the metal is through the enol-imine tautomeric form, and the anomeric equilibrium remains in dimethyl sulfoxide solutions. This complex was also obtained by reaction of D-glucosamine with Ni(II) salicylaldehydate. The same reaction was employed for the synthesis of bis-N-[2-deoxy-D-galactopyranosyl-2-(2-hydroxybenzaldiminate)]Ni(II). The small paramagnetic shifts of the 1H NMR resonances of the complexes suggest that paramagnetic species are present in low proportions.