Porphyromonas gingivalis is a nonmotile, obligate anaerobic, Gram-negative bacterium known for its association with periodontal disease and its involvement in systemic diseases such as ...atherosclerosis, cardiovascular disease, colon cancer, and Alzheimer's disease. This bacterium produces several virulence factors, including capsules, fimbriae, lipopolysaccharides, proteolytic enzymes, and hemagglutinins. A comparative genomic analysis revealed the open pangenome of P. gingivalis and identified complete type IV secretion systems in strain KCOM2805 and almost complete type VI secretion systems in strains KCOM2798 and ATCC49417, which is a new discovery as previous studies did not find the proteins involved in secretion systems IV and VI. Conservation of some virulence factors between different strains was observed, regardless of their genetic diversity and origin. In addition, we performed for the first time a reconstruction analysis of the gene regulatory network, identifying transcription factors and proteins involved in the regulatory mechanisms of bacterial pathogenesis. In particular, QseB regulates the expression of hemagglutinin and arginine deaminase, while Rex may suppress the release of gingipain through interactions with PorV and the formatum/nitrate transporter. Our study highlights the central role of conserved virulence factors and regulatory pathways, particularly QseB and Rex, in P. gingivalis and provides insights into potential therapeutic targets.
Compound 5-{(2E)-3-bromo-3-carboxyprop-2-enoylamino}-2-hydroxybenzoic acid (C1), a new 5-aminosalicylic acid (5-ASA) derivative, has proven to be an antioxidant in vitro and an anti-inflammatory ...agent in mice. The in vivo inhibition of myeloperoxidase was comparable to that of indomethacin. The aim of this study was to take another step in the preclinical evaluation of C1 by examining acute toxicity with the up-and-down OECD method and pharmacokinetic profiles by administration of the compound to Wistar rats through intravenous (i.v.), oral (p.o.), and intraperitoneal (i.p.) routes. According to the Globally Harmonized System, C1 belongs to categories 4 and 5 for the i.p. and p.o. routes, respectively. An RP-HPLC method for C1 quantification in plasma was successfully validated. Regarding the pharmacokinetic profile, the elimination half-life was approximately 0.9 h with a clearance of 24 mL/min after i.v. administration of C1 (50 mg/kg). After p.o. administration (50 mg/kg), the maximum plasma concentration was reached at 33 min, the oral bioavailability was about 77%, and the compound was amply distributed to all tissues evaluated. Therefore, C1 administered p.o. in rats is suitable for reaching the colon where it can exert its effect, suggesting an important advantage over 5-ASA and indomethacin in treating ulcerative colitis and Crohn’s disease.
Objective
To establish nomograms for linear measurements of the frontal and occipital horns of the lateral ventricle and their relationship, in pregnant patients between 18 and 40 weeks of gestation ...and having attended 2 units of Maternal Fetal Medicine in Bogotá—Colombia.
Methodology
A descriptive cross‐sectional study with an analytical component was carried out on pregnant patients who utilized the ultrasound services at 2 Maternal‐Fetal Medicine units in Bogotá, between 18 and 40 weeks of pregnancy who underwent measurement. From the anterior and posterior horns of the lateral ventricles, the fronto‐occipital ratio was calculated at each gestational week, and nomograms were created for each of these variables.
Results
Nine hundred and seventy‐eight patients were included in the study. The distance of the frontal horns ranged between 6.9 and 51.6 mm with a mean of 19.1 ± 5.8 mm; that of the occipital horns had a measurement between 8.7 and 53 mm with a mean of 28, 1 ± 8.9 mm; on the other hand, the fronto‐occipital ratio (FOR) yielded a mean of 0.365 ± 0.067 (0.136–0.616) without bearing any relation to gestational age. The trend of normal values for the studied population is displayed, plotted in percentile curves and nomograms for each gestational age.
Conclusion
The measurement of the frontal and occipital horns, and the calculation of the fronto‐occipital relationship is technically possible between 18 and 40 weeks, finding that the anterior and posterior horns have a positive linear relationship with gestational age. Contrarily, the FOR does not correlate with the gestational age, it was possible to establish a table of percentiles that allows determining the normal values for these measurements during pregnancy.
The measurement of the fronto‐occipital relationship (FOR) could be relevant for the diagnosis and follow‐up of fetal patients with ventriculomegaly. There are currently no nomograms that help us evaluating the fetal central nervous system. These allowed us to create nomograms of the measurements of the anterior and posterior horns and to describe the relationship between them.
5-(4-carboxybutanoyl)amino-2-hydroxybenzoic acid (C2) is a novel synthetic derivative of 5-aminosalicylic acid (5-ASA), which is currently being evaluated ex vivo as an anti-inflammatory agent and ...has shown satisfactory results. This study aimed to obtain the pharmacokinetic profiles, tissue distribution and plasma protein binding of C2 in Wistar Rats. Additionally, an HPLC method was developed and validated to quantify C2 in rat plasma. The pharmacokinetic profiles of intragastric, intravenous and intraperitoneal administration routes at singles doses of 100, 50, and 100 mg/kg, respectively, were studied in Wistar rats. The elimination half-life of intravenously administered C2 was approximately 33 min. The maximum plasma level of C2 was reached approximately 24 min after intragastric administration, with a Cmax value of 2.5 g/mL and an AUCtot value of 157 μg min-1/mL; the oral bioavailability was approximately 13%. Following a single intragastric or oral dose (100 mg/kg), C2 was distributed and detected in all examined tissues (including the brain and colon). The results showed that C2 accumulates over time. The plasma protein binding results indicated that the unbound fraction of C2 at concentrations of 1 to 20 μg/mL ranged from 89.8% to 92.5%, meaning that this fraction of C2 is available to cross tissues. Finally, the blood-plasma partitioning (BP ratio) of C2 in rat plasma was 0.71 and 0.6 at concentrations of 5 and 10 μg/mL, respectively, which indicates that C2 is free in the plasmatic phase and not inside blood cells. The results of this study suggest that a fraction of the administered C2 dose is absorbed in the stomach, and the fraction that is not absorbed reaches the small intestine and colon. This distribution constitutes the main advantage of C2 compared with 5-ASA for the treatment of ulcerative colitis (UC) and Crohn's disease (CD).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pteropodine (PT) is a component of some plants with potentially useful pharmacological activities for humans. This compound has biomedical properties related to the modulation of the immune system, ...nervous system, and inflammatory processes. This study addresses the anti-inflammatory and antioxidant capacity of pteropodin in a murine model of arthritis and induced edema of the mouse ear. To evaluate the anti-inflammatory activity, we used the reversed passive Arthus reaction (RPAR), which includes the rat paw edema test, the rat pleurisy test, and a mouse ear edema model. The antioxidant effect of PT was evaluated by determining the myeloperoxidase enzyme activity. PT showed an anti-inflammatory effect in the different specific and non-specific tests. We found a 51, 66 and 70% inhibitory effect of 10, 20 and 40 mg/kg of PT, respectively, in the rat paw edema test. In the pleurisy assay, 40 mg/kg of PT induced a low neutrophil count (up to 36%) when compared to the negative control group, and 20 mg/kg of PT increased the content of lymphocytes by up to 28% and the pleural exudate volume decreased by 52% when compared to the negative control group, respectively. We also found an 81.4% inflammatory inhibition of the edema ear with 0.04 mg/ear of PT, and a significant myeloperoxidase enzyme inhibition by the three doses of PT tested. We conclude that PT exerted a potent anti-inflammatory effect in the acute inflammation model in rodents.
La neuroética es una disciplina que ha surgido para actuar preventivamente ante el uso de estrategias o experimentos basados en neurociencia que pudieran atentar contra los derechos de privacidad, ...intimidad, salud y vida de las personas. El objetivo de esta investigación fue determinar el impacto de la neuroética en el clima laboral de una empresa industrial peruana. Desde la perspectiva metodológica, la investigación es de orden cualitativo, paradigma hermenéutico interpretativo y estudio de caso; inicia con la entrevista a profundidad a los trabajadores de la empresa en estudio. Los resultados indican que sus integrantes tienen una importante identificación con los objetivos de la organización, en donde sus administradores son reconocidos como líderes transformacionales, mismo que deben asumir su rol y resultados económicos a la entidad. Se concluye que hay evidente influencia de la neuroética en el clima laboral, aplicada empíricamente al comprobarse sus características determinantes, como la ética, la moral e instintos sociales, en virtud a la existencia de una adecuada estructura de la organización.
Automated methods that can identify white matter bundles from large tractography datasets have several applications in neuroscience research. In these applications, clustering algorithms have shown ...to play an important role in the analysis and visualization of white matter structure, generating useful data which can be the basis for further studies. This work proposes FFClust, an efficient fiber clustering method for large tractography datasets containing millions of fibers. Resulting clusters describe the whole set of main white matter fascicles present on an individual brain. The method aims to identify compact and homogeneous clusters, which enables several applications. In individuals, the clusters can be used to study the local connectivity in pathological brains, while at population level, the processing and analysis of reproducible bundles, and other post-processing algorithms can be carried out to study the brain connectivity and create new white matter bundle atlases. The proposed method was evaluated in terms of quality and execution time performance versus the state-of-the-art clustering techniques used in the area. Results show that FFClust is effective in the creation of compact clusters, with a low intra-cluster distance, while keeping a good quality Davies–Bouldin index, which is a metric that quantifies the quality of clustering approaches. Furthermore, it is about 8.6 times faster than the most efficient state-of-the-art method for one million fibers dataset. In addition, we show that FFClust is able to correctly identify atlas bundles connecting different brain regions, as an example of application and the utility of compact clusters.
•We propose an efficient clustering algorithm for diffusion-based white matter fibers.•It is based on a fiber point clustering and a graph modeling of similar clusters.•It can process a 2.7 million fiber dataset on 4.4 minutes on a desktop computer.•It provides compact and regular clusters, representing the whole brain WM structure.
During the inflammation process, myeloperoxidase (MPO) contributes to the production of reactive species mainly for the destruction of pathogens. When inflammation is dysregulated, the overproduction ...of reactive species generates cellular damage via the oxidation of biomolecules (proteins, lipids and nucleic acids) that are associated with many acute or chronic inflammatory diseases, including cardiovascular and neurodegenerative disorders, dermatitis, ulcerative colitis, and cancer. Therefore, MPO plays a crucial role in inflammation and oxidative stress, representing an interesting target for drug design. Hence, in this work, four 5-aminosalicylic acid derivatives (C1–C4) were synthesized and evaluated. The results showed that C1has anti-inflammatory activity (ear model) comparable to indomethacin, while C2, C3 and C4 showed better MPO inhibitory effects when evaluated in vitro using the O-dianisidine method; however, in the in silico analyses, C3 and C4 were coupled on MPO under the better geometric and free energy values than the other tested compounds. In addition, compounds C3 and C4 showed good antioxidant properties according to the in vitro assays using the 2,2′-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid methods. Taken together, these findings suggest that C1–C4 may be useful for the treatment of several inflammatory diseases in the future.
Introduction. The identity of Staphylococcus aureus virulence factors involved in chronic osteomyelitis remains unresolved. SapS is a class C non-specific acid phosphatase and a well-known virulence ...factor that has been identified in S. aureus strain 154 but in protein extracts from rotting vegetables.Objective. To identify the SapS gene and characterize the activity of SapS from S. aureus strains: 12 isolates from bone infected samples of patients treated for chronic osteomyelitis and 49 from a database with in silico analysis of complete bacterial genomes.Materials and methods. The SapS gene was isolated and sequenced from 12 S. aureus clinical isolates and two reference strains; 49 S. aureus strains and 11 coagulase-negative staphylococci were tested using in silico PCR. Culture media semi-purified protein extracts from the clinical strains were assayed for phosphatase activity with p-nitro-phenylphosphate, O-phospho-L-tyrosine, O-phospho-L-serine, and OphosphoL-threonine in conjunction with various phosphatase inhibitors.Results. SapS was detected in the clinical and in-silico S. aureus strains, but not in the in silico coagulase-negative staphylococci strains. Sec-type I lipoprotein-type N-terminal signal peptide sequences; secreted proteins, and aspartate bipartite catalytic domains coding sequences were found in the SapS nucleotide and amino acid sequence analysis. SapS dephosphorylated with p-nitro-phenyl-phosphate and ophosphoLtyrosine were selectively resistant to tartrate and fluoride, but sensitive to vanadate and molybdate.Conclusion. SapS gene was found in the genome of the clinical isolates and the in silico Staphylococcus aureus strains. SapS shares biochemical similarities with known virulent bacterial, such as protein tyrosine phosphatases, suggesting it may be a virulence factor in chronic osteomyelitis.
Naegleria fowleri produces a fatal disease called primary amebic meningoencephalitis (PAM), which is characterized by an extensive inflammatory reaction in the CNS. It is known that the immune ...response is orchestrated mainly by neutrophils, which activate several defense mechanisms in the host, including phagocytosis, the release of different enzymes such as myeloperoxidase (MPO), and the production of neutrophil extracellular traps. However, the mechanisms by which amoebas evade the neutrophil response are still unknown. In this study, we analyzed the ability of N. fowleri to respond to the stress exerted by MPO. Interestingly, after the interaction of trophozoites with neutrophils, the amoeba viability was not altered; however, ultrastructural changes were observed. To analyze the influence of MPO against N. fowleri and its participation in free radical production, we evaluated its enzymatic activity, expression, and localization with and without the specific 4‐aminobenzoic acid hydrazide inhibitor. The production of oxidizing molecules is the principal mechanism used by neutrophils to eliminate pathogens. In this context, we demonstrated an increase in the production of NO, superoxide anion, and reactive oxygen species; in addition, the overexpression of several antioxidant enzymes present in the trophozoites was quantified. The findings strongly suggest that N. fowleri possesses antioxidant machinery that is activated in response to an oxidative environment, allowing it to evade the neutrophil‐mediated immune response, which may contribute to the establishment of PAM.
Shows Naegleria fowleri has antioxidant machinery that is activated in response to an oxidative environment, allowing it to evade the neutrophil‐mediated immune response and perhaps contributing to amebic meningoencephalitis.
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