Cholesterol is an essential component of cell membranes and the precursor for the synthesis of steroid hormones and bile acids. The synthesis of this molecule occurs partially in a membranous world ...(especially the last steps), where the enzymes, substrates, and products involved tend to be extremely hydrophobic. The importance of cholesterol has increased in the past half-century because of its association with cardiovascular diseases, which are considered one of the leading causes of death worldwide. In light of the current need for new drugs capable of controlling the levels of cholesterol in the bloodstream, it is important to understand how cholesterol is synthesized in the organism and identify the main enzymes involved in this process. Taking this into account, this review presents a detailed description of several enzymes involved in the biosynthesis of cholesterol. In this regard, the structure and catalytic mechanism of the enzymes involved in cholesterol biosynthesis, from the initial two-carbon acetyl-CoA building block, will be reviewed and their current pharmacological importance discussed. We believe that this review may contribute to a deeper level of understanding of cholesterol metabolism and that it will serve as a useful resource for future studies of the cholesterol biosynthesis pathway.
Salt iodization is the main public health policy to prevent and control iodine deficiency disorders. The National Salt Iodization Impact Assessment Survey (PNAISAL) was conducted to measure iodine ...concentration among Brazilian schoolchildren. A survey including 6-14-year-old schoolchildren from public and private schools from all 26 Brazilian states and the Federal District was carried out in the biennia 2008-2009 and 2013-2014. Municipalities, schools, and students were randomly selected. Students were interviewed at school using a standard questionnaire, which included the collection of demographic, educational, weight, height, and 10 mL non-fasting urine collection information. The analyses were weighted according to the population of students per federative unit. The median urinary iodine concentration (MUIC) for the entire sample by region, federative unit per school, and student characteristics, was described from the cutoff points defined by the World Health Organization (severe disability: <20 µg/L, moderate: 20-49 µg/L, mild: 50-99 µg/L, adequate: 100-199 µg/L, more than adequate: 200-299 µg/L, and excessive: >300 µg/L). In total, 18,864 students (95.9% of the total) from 818 schools in 477 municipalities from all federative units were included in this study. Almost 70% were brown skin color, nine-years-old or older, studied in urban schools, and were enrolled in elementary school. The prevalence of overweight/obesity, as measured by body mass index (BMI) for age, was about twice as high compared to nutritional deficits (17.3% versus 9.6%). The MUIC arrived at 276.7 µg/L (25th percentile = 175.5 µg/L and 75th percentile = 399.71 µg/L). In Brazil as a whole, the prevalence of mild, moderate, and severe deficit was 6.9%, 2.6%, and 0.6%, respectively. About one-fifth of the students (20.7%) had adequate iodine concentration, while 24.9% and 44.2% had more than adequate or excessive concentration, respectively. The prevalence of iodine deficits was significantly higher among younger female students from municipal public schools living in rural areas with the lowest BMI. The median urine iodine concentration showed that Brazilian students have an adequate nutritional intake, with a significant proportion of them evidencing overconsumption of this micronutrient.
Brain Long non-coding RNA (lncRNA) and microRNAs (miRs) play essential roles in the regulation of several important biological processes, including neuronal activity, cognitive processes, ...neurogenesis, angiogenesis, and neuroinflammation. In this context, the transcriptional repressor, RE1 silencing transcription factor (Rest), acts regulating the expression of neuronal genes as well as of lncRNAs and multiple miRNAs in the central nervous system. Nevertheless, its role in neuroinflammation was less explored. Here, we demonstrate, using an in vivo model of neuroinflammation induced by i.p. injection of LPS (0.33 mg/kg), that neuroinflammation increases gene expression of pro-inflammatory cytokines concomitant with the native and truncated forms of Rest and of non-coding RNAs. Additionally, the increased expression of enzymes Drosha ribonuclease III) (Drosha), Exportin 5 (Xpo5) and Endoribonuclease dicer (Dicer), associated with high expression of neuroprotective miRs 22 and 132 are indicative that the activation of biogenesis of miRs in the hippocampal region is a Central Nervous System (CNS) protective mechanism for the deleterious effects of neuroinflammation. Our results indicate that positive regulation of Rest gene expression in the hippocampal region by neuroinflammation correlates directly with the expression of miRs 22 and 132 and inversely with miR 335. In parallel, the confirmation of the possible alignment between the lncRNAs with miR 335 by bioinformatics corroborates with the sponge effect of Hottip and Hotair hybridizing and inhibiting the pro-inflammatory action of miR 335. This suggests the existence of a possible correlation between the activation of miR biogenesis machinery with increased expression of the transcription factor Rest, contributing to neuroprotection.
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•Involvement of ncRNAs in the neuroprotective response LPS-induced inflammation hippocampal.•Neuroinflammation activates the miRs biogenesis machinery in the hippocampus.•LPS-induced inflammation modulates miR22, 132 and 355 expressions in the hippocampus.•Hippocampal neuroinflammation modifies the transcriptional profile of lncRNA Hotair and Hottip.
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•Computational aided drug design (CADD) in drug discovery and development.•Review about the main stages, strengths and limitations, of a virtual screening campaign.•Practical issues ...and the Achilles heel of the virtual screening protocols.
Computational aided drug design (CADD) is presently a key component in the process of drug discovery and development as it offers great promise to drastically reduce cost and time requirements.
In the pharmaceutical arena, virtual screening is normally regarded as the top CADD tool to screen large libraries of chemical structures and reduce them to a key set of likely drug candidates regarding a specific protein target. This chapter provides a comprehensive overview of the receptor-based virtual screening process and of its importance in the present drug discovery and development paradigm. Following a focused contextualization on the subject, the main stages of a virtual screening campaign, including its strengths and limitations, are the subject of particular attention in this review. In all of these stages special consideration will be given to practical issues that are normally the Achilles heel of the virtual screening process.
•Novelty detection is proposed as a novel paradigm for US NDT of wind turbines blades.•ND considers one class classification and does not require signatures from defects.•The proposed signal ...processing chain comprises both FFT and PCA.•A performance comparison among different novelty detection methods is presented.•The results are evaluated considering a practical ultrasonic NDT scenario.
Among the renewable energy sources, wind power generation presents competitive costs and high installation potential in many countries. Ensuring the integrity of the generation equipment plays an important role for reliable energy production. Therefore, nondestructive test procedures are required, especially for turbine blades, which are subject to severe operational conditions due to phenomena such as lightning strikes, mechanical stress, humidity and corrosion. Nondestructive ultrasonic test techniques are commonly applied in their predictive maintenance. This work proposes the use of novelty detection methods combined with nondestructive ultrasound testing to identify structural problems in wind turbine blades. Ultrasound signals are preprocessed using both, wavelet denoising and principal component analysis. Novelty detection deals with the one-class classification problem, when only the normal condition signatures are required for the classification system design. For the nondestructive test of turbine blades, this is an interesting paradigm because it is not always possible to obtain test samples from all of the existing flaw conditions. Our experimental results indicate the efficiency of the proposed method.
Electrocatalytic production of H2O2 via a two-electron oxygen reduction reaction (ORR-2e–) is regarded as a highly promising decentralized and environmentally friendly mechanism for the production of ...this important chemical commodity. However, the underlying challenges related to the development of catalytic materials that contain zero or low content of noble metals and that are relatively more active, selective, and resistant for long-term use have become a huge obstacle for the electroproduction of H2O2 on commercial and industrial scales. The present study reports the synthesis and characterization of low metal-loaded (≤6.4 wt %) catalysts and their efficiency in H2O2 electroproduction. The catalysts were constructed using gold palladium molybdenum oxide (AuPdMoO x ) and palladium molybdenum oxide (PdMoO x ) nanoparticles supported on graphene nanoribbons. Based on the application of a rotating ring-disk electrode, we conducted a thorough comparative analysis of the electrocatalytic performance of the catalysts in the ORR under acidic and alkaline media. The proposed catalysts exhibited high catalytic activity (ca. 0.08 mA gnoble metal –1 in an acidic medium and ca. 6.6 mA gnoble metal –1 in an alkaline medium), good selectivity (over 80%), and improved long-term stability toward ORR-2e–. The results obtained showed that the enhanced ORR activity presented by the catalysts, which occurred preferentially via the two-electron pathway, was promoted by a combination of factors including geometry, Pd content, interparticle distance, and site-blocking effects, while the electrochemical stability of the catalysts may have been enhanced by the presence of MoO x .
COVID-19 has generated a scenario for global health with multiple systemic impairments. This retrospective study evaluated the clinical, radiological, and pulmonary functional evolution in 302 ...post-COVID-19 patients. Regarding post-COVID-19 pulmonary symptoms, dry cough, dyspnea, and chest pain were the most frequent. Of the associated comorbidities, asthma was more frequent (23.5%). Chest tomography (CT) initially showed a mean pulmonary involvement of 69.7%, and evaluation in the subsequent months showed improvement in the evolutionary image. With less than six months post-pathology, there was a commitment of 37.7% from six to twelve months it was 20%, and after 12 months it was 9.9%. As for most of the sample, 50.3% of the patients presented CT normalization less than six months after infection, 23% were normalized between six and twelve months, and 5.2% presented with normalized images after twelve months, with one remaining. A percentage of 17.3% maintained post-COVID-19 pulmonary residual sequelae. Regarding spirometry, less than six months after pathology, 59.3% of the patients presented regular exam results, 12.3% had their function normalized within six to twelve months, and 6.3% had normal exam results twelve months after their post-pathology evaluation. Only 3.6% of the patients still showed some alteration during this period.
FT special report: Cobalt nanoparticles with a size of around 7.7 nm prepared in 1‐alkyl‐3‐methylimidazolium bis(trifluoromethanesulfonyl)imidate ionic liquids are effective catalysts for the ...Fischer–Tropsch (FT) synthesis, yielding olefins, oxygenates, and paraffins (C7–C30). The nanoparticles are easily prepared by the decomposition of Co(CO)8 in the ionic liquid at 150 °C and can be reused at least three times if they are not exposed to air.
This work aimed to synthesize poly (D, L-lactic-co-glycolic acid) (PLGA) microparticles containing hinokinin (HNK) and to evaluate their cytotoxic activity against tumoral SiHa cells and non-tumoral ...HaCaT cells. Hinokinin was incorporated into PLGA (PLGA-HNK) with an encapsulation efficiency of 84.18 ± 2.32%. PLGA and PLGA-HNK were characterized by SEM microscopy and showed spherical morphology with an average size of ∼3.33. Encapsulation efficiency was determined by a calibration curve using UV-vis spectroscopy. PLGA-HNK more active inhibiting proliferation of SiHa cells (IC50 = 14.68 µM) than free HNK (IC50 = 225.5 µM). In relation to HaCaT cells, PLGA-HNK showed no significant difference compared to the negative control. These results led to an increase in HNK bioavailability and thereby, biological activity. In silico prediction analysis suggests that HNK is cytotoxic against SiHa cells with E6 and MDM2 inhibition as possible main mechanism of action.
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