RESUMEN

This work proposes a novel method to determine the Cd(II) and Cr(III) content in commercial sugar samples. It is based on the extraction of the analytes (as ammonium pyrrolidine dithiocarbamate complexes) into a semipermeable membrane device (SPMD) filled with CHCl3. After extraction, the SPMD was deployed and opened, and the analytes were recovered from the organic phase by back extraction with a 4.2 mol L-1 HNO3 solution. The analytes present in the acid extract were measured with graphite furnace atomic absorption spectrometry. Under optimized conditions, the limit of quantification of the method was 1.2 and 3.1 ng g-1 for Cd(II) and Cr(III), respectively. Twelve samples of different types of sugar were analyzed. In addition, a recovery test was performed to evaluate the accuracy of the method. The recovery percentage was 90 %-102 % for Cd(II) and 85.2 %-103 % for Cr(III).

RESUMEN

BACKGROUND: Prognostication in glomerulonephritis with severe kidney function impairment is critical for evaluating the benefit-to-risk ratio of immunosuppression. We hypothesized that the urine biomarker epidermal growth factor (EGF) could have good discrimination power to identify subjects who might ultimately recover kidney function. METHODS: We included 82 subjects with glomerulonephritis and severe kidney function impairment at admission (estimated glomerular filtration rate [eGFR] ≤ 30 mL/min/1.73m2): 58 with lupus nephritis (LN) and 24 with ANCA-associated vasculitis (AAV). Thirty-five subjects required kidney replacement therapy (KRT) at presentation. Urine epidermal growth factor was measured and corrected by urine creatinine (uEGF/Cr) and the population was analyzed by uEGF/Cr tertiles. The primary outcome was time to recovery of eGFR ≥ 30 mL/min/1.73m2 and time to recovery of kidney function with dialysis independence in those with initial KRT. RESULTS: Forty-four (54%) participants met the primary outcome of recovery of eGFR ≥ 30 mL/min/1.73m2. The 6-month recovery rates were 93%, 57%, and 0% for participants in the highest, middle, and lowest uEGF/Cr tertile, respectively. Recovery of the kidney function was faster and led to a higher post-therapy eGFR in the highest uEGF/Cr tertile. In the ROC analysis, uEGF/Cr was a predictor of recovery with an area under the curve (AUC) of 0.92 (95% CI 0.87-0.98), and a cutoff of 2.60 ng/mg had 100% sensitivity to detect patients who recovered kidney function. In the subgroup of participants with initial KRT, the cut-off of uEGF/Cr of 2.0 ng/mg had 100% sensitivity to detect participants who recovered kidney function with dialysis independence by 6 months. CONCLUSIONS: Urine EGF/Cr is a promising biomarker to aid in the prediction of recovery of kidney function in glomerulonephritis with severe kidney function impairment.

RESUMEN

This paper reports a comprehensive study of Theobroma cacao pericarp (TCP) residues, which has been prepared, characterized, and tested as an inexpensive and efficient biosorbent of Cr(VI) from aqueous solutions. The maximum adsorption capacity of TCP obtained at optimal conditions (pH = 2, dose = 0.5 g L-1, C0 = 100 mg L-1) was qmax = 48.5 mg g-1, which is one of the highest values reported by the literature. Structural and morphological characterization has been performed by FTIR, SEM/EDX, and pHPZC measurements. FTIR analysis revealed the presence of O-H, -NH, -NH2, C = H, C = O, C = C, C-O, and C-C functional groups that would be involved in the Cr(VI) biosorption processes. The experimental equilibrium data of biosorption process were successfully fitted to non-linear Langmuir (R2 = 0.95, χ2 = 11.0), Freundlich (R2 = 0.93, χ2 = 14.8), and Temkin (R2 = 0.93, χ2 = 14.7) isotherm models. Kinetics experimental data were well adjustment to non-linear pseudo-2nd (R2 = 0.99, χ2 = 2.08)- and pseudo-1st-order kinetic models (R2 = 0.98, χ2 = 2.25) and also to intra-particle Weber-Morris (R2 = 0.98) and liquid film diffusion (R2 = 0.99) models. These results indicate that Cr(VI) biosorption on heterogeneous surfaces as well as on monolayers of TCP would be a complex process controlled by chemisorption and physisorption mechanisms. The thermodynamic results indicate that the Cr(VI) biosorption on TCP is a feasible, spontaneous, and endothermic process. TCP can be regenerated with NaOH and reused up to 3 times.

Asunto(s)

RESUMEN

Respiratory syncytial virus (RSV) is a common respiratory pathogen that causes respiratory illnesses, ranging from mild symptoms to severe lower respiratory tract infections in infants and older adults. This virus is responsible for one-third of pneumonia deaths in the pediatric population; however, there are currently only a few effective vaccines. A better understanding of the RSV-host relationship at the molecular level may lead to a more effective management of RSV-related symptoms. The fractalkine (CX3CL1) receptor (CX3CR1) is a co-receptor for RSV expressed by airway epithelial cells and diverse immune cells. RSV G protein binds to the CX3CR1 receptor via a highly conserved amino acid motif (CX3C motif), which is also present in CX3CL1. The CX3CL1-CX3CR1 axis is involved in the activation and infiltration of immune cells into the infected lung. The presence of the RSV G protein alters the natural functions of the CX3CR1-CX3CL1 axis and modifies the host's immune response, an aspects that need to be considered in the development of an efficient vaccine and specific pharmacological treatment.

Asunto(s)

RESUMEN

Bis-heterocycles were synthesized via a consecutive one-pot process by a Groebke-Blackburn-Bienaymé reaction (GBB-3CR) followed by Copper-catalyzed Alkyne-Azide Cycloaddition (CuAAC) assisted by alternative sustainable energies (ASE) such as ultrasonic and mechanical. These efficient and convergent strategies allowed the in situ generation of complex azides functionalized with imidazo[1,2-a]pyridines (IMPs), which was used as a synthetic platform. The target molecules contain two privileged scaffolds in medicinal chemistry: IMPs and the heterocyclic bioisostere of trans-amide bond, the 1,4-disubstituted 1H-1,2,3-triazoles (1,4-DS-1,2,3-Ts).

RESUMEN

Environmental contamination by chromium represents a serious public health problem. Therefore, it is crucial to develop and optimize remediation technologies to reduce its concentration in the environment. The aims of this study were to evaluate the uptake of chromium by live and complete microbial mats in experimental mesocosms under different pH and salinity conditions to understand how these factors affect the microphytobenthic community and, consequently, how chromium removal process is influenced. Microbial mats from the estuarine environment were exposed to 15 mg Cr/L under different pH (2, 4, and 8) and salinity (2, 15, and 33) conditions. Salinity, redox potential, and pH were measured throughout the trial in solutions and in microbial mats, while total Cr determinations were performed at the end of the assay. The results demonstrated that the removal efficiency of Cr by microbial mats was significantly improved in solutions at pH 2, remaining unaffected by variations in salinity. Notably, both cyanobacteria and diatoms showed remarkable resistance to Cr exposure under all conditions tested, highlighting their exceptional adaptability. Microbial mats have proved to be effective filters for reducing the concentration of chromium in aqueous solutions with varying pH and salinity levels.

Asunto(s)

RESUMEN

The aim of this study was to verify the effectiveness of attenuated total reflectance-fourier transform infrared (ATR-FTIR) spectroscopy in the characterization of bone repair in mandibular osteotomy using erbium, chromium-doped yttrium, scandium, gallium and garnet (Er,Cr:YSGG) laser and multilaminate drill on each side. Two mandible bone fragments were removed from 30 rabbits, and the process of bone repair was studied immediately, 3, 7, 15, 21, and 28 days after the surgery. The histological analysis allowed detecting differences in the early stages of tissue repair after bone cutting performed with the Er,Cr:YSGG laser or multilaminate drill. The ATR-FTIR spectroscopy technique was sensitive to changes in the organic content of bone tissue repair process.

Asunto(s)

RESUMEN

Cu2ZnSnSe4 (CZTSe) nanoparticles (NPs) were successfully synthesized via a solvothermal method. Their structural, compositional, morphological, optoelectronic, and electrochemical properties have been characterized by X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), Field-emission scanning electron microscopy (FE-SEM), transmission electron microscope (TEM), UV-vis absorption spectroscopy, and electrochemical impedance spectroscopy (EIS) techniques. Porosimetry and specific surface area in terms of the Brunauer-Emmett-Teller (BET) technique have also been studied. XRD indicates the formation of a polycrystalline kesterite CZTSe phase. Raman peaks at 173 and 190 cm-1 confirm the formation of a pure phase. TEM micrographs revealed the presence of nanoparticles with average sizes of ~90 nm. A BET surface area of 7 m2/g was determined. The CZTSe NPs showed a bandgap of 1.0 eV and a p-type semiconducting behavior. As a proof of concept, for the first time, the CZTSe NPs have been used as a visible-light-driven photocatalyst to Congo red (CR) azo dye degradation. The nanophotocatalyst material under simulated sunlight results in almost complete degradation (96%) of CR dye after 70 min, following a pseudo-second-order kinetic model (rate constant of 0.334 min-1). The prepared CZTSe was reusable and can be repeatedly used to remove CR dye from aqueous solutions.

RESUMEN

Over the last two decades, the incidence of Invasive Fungal Infections (IFIs) globally has risen, posing a considerable challenge despite available antifungal therapies. Addressing this, the World Health Organization (WHO) prioritized research on specific fungi, notably Histoplasma spp. and Paracoccidioides spp. These dimorphic fungi have a mycelial life cycle in soil and a yeast phase associated with tissues of mammalian hosts. Inhalation of conidia and mycelial fragments initiates the infection, crucially transforming into the yeast form within the host, influenced by factors like temperature, host immunity, and hormonal status. Survival and multiplication within alveolar macrophages are crucial for disease progression, where innate immune responses play a pivotal role in overcoming physical barriers. The transition to pathogenic yeast, triggered by increased temperature, involves yeast phase-specific gene expression, closely linked to infection establishment and pathogenicity. Cell adhesion mechanisms during host-pathogen interactions are intricately linked to fungal virulence, which is critical for tissue colonization and disease development. Yeast replication within macrophages leads to their rupture, aiding pathogen dissemination. Immune cells, especially macrophages, dendritic cells, and neutrophils, are key players during infection control, with macrophages crucial for defense, tissue integrity, and pathogen elimination. Recognition of common virulence molecules such as heat- shock protein-60 (Hsp60) and enolase by pattern recognition receptors (PRRs), mainly via the complement receptor 3 (CR3) and plasmin receptor pathways, respectively, could be pivotal in host-pathogen interactions for Histoplasma spp. and Paracoccidioides spp., influencing adhesion, phagocytosis, and inflammatory regulation. This review provides a comprehensive overview of the dynamic of these two IFIs between host and pathogen. Further research into these fungi's virulence factors promises insights into pathogenic mechanisms, potentially guiding the development of effective treatment strategies.

RESUMEN

BACKGROUND: The evaluation of the quality of life (QoL) of patients with colorectal cancer (CRC) is an essential measure to measure the impact of the disease and treatments on the lives of patients. However, in Latin America there is no validated and reliable instrument to assess this construct. OBJECTIVES: This study aims to validate the EORTC QLQ-CR29 instrument in the Mexican population with CRC. METHODS: This study aims to validate the EORTC QLQ-CR29 instrument in the Mexican population with CRC. The study used an instrumental design and a nonprobabilistic sample due to availability, made up of 251 patients with CRC, with an average age of 54.7 ± 12.28 years. Exploratory and confirmatory factor analyses were performed, as well as concurrent validity tests. RESULTS: The exploratory factorial analysis yielded 4 factors that explained 51.64% of the variance, with a Cronbach reliability coefficient of .766 and an Omega index of .725. The confirmatory factor analysis indicated that the proposed theoretical model fits the data almost perfectly, with an error close to 0, which shows that it is a balanced and parsimonious instrument to measure the QoL of the patients with CRC. SIGNIFICANCE OF RESULTS: The EORTC QLQ-CR29 instrument proved to be a valid and reliable instrument for use in clinical care and research directed at patients with CRC in Mexico. Its use is recommended by multidisciplinary health teams in oncology in Mexico, since it allows knowing the patient's perspective on the impact of CRC on their life, guiding therapeutic decision-making and being a primary outcome measure.

RESUMEN

The human Respiratory Syncytial Virus (hRSV) stands as one of the most common causes of acute respiratory diseases. The infectivity of this virus is intricately linked to its membrane proteins, notably the attachment glycoprotein (G protein). The latter plays a key role in facilitating the attachment of hRSV to respiratory tract epithelial cells, thereby initiating the infection process. The present study aimed to characterize the interaction of the conserved cysteine-noose domain of hRSV G protein (cndG) with the transmembrane CX3C motif chemokine receptor 1 (CX3CR1) isoforms using computational tools of molecular modeling, docking, molecular dynamics simulations, and binding free energy calculations. From MD simulations of the molecular system embedded in the POPC lipid bilayer, we showed a stable interaction of cndG with the canonical fractalkine binding site in the N-terminal cavity of the CX3CR1 isoforms and identified that residues in the extracellular loop 2 (ECL2) region and Glu279 of this receptor are pivotal for the stabilization of CX3CR1/cndG binding, corroborating what was reported for the interaction of the chemokine fractalkine with CX3CR1 and its structure homolog US28. Therefore, the results presented here contribute by revealing key structural points for the CX3CR1/G interaction, allowing us to better understand the biology of hRSV from its attachment process and to develop new strategies to combat it.

RESUMEN

The imidazo[1,2-a]pyridine moiety is present in drugs with several biological activities. The most direct way of obtaining this nucleus is the Groebke-Blackburn-Bienaymé three-component reaction (GBB-3CR) between aminopyridines, aldehydes, and isocyanides under both Lewis and Brønsted acid catalysis. However, several catalysts for this reaction have major drawbacks such as being expensive, extremely dangerous, strong oxidizing, and even explosive. In this scenario, heteropolyacids emerge as greener and safer alternatives due to their very strong Brønsted acidity. In particular, phosphotungstic acid (HPW) is an economical and green attractive catalyst for being cheap, non-toxic, and is known for its chemical and thermal stability. Herein, we report a straightforward approach to the GBB-3CR using HPW as catalyst in ethanol under microwave (µw) heating. This convenient environmentally benign methodology is broad in scope, provides the heterobicyclic products in high yields (up to 99%), with a low catalyst loading (2 mol %) in only 30 minutes, and allows the successful use of aliphatic aldehydes, substrates not so frequently explored with most usual catalysts for this reaction. Furthermore, the aforementioned advantages make this methodology very attractive and superior to the existing ones.

RESUMEN

OBJECTIVE: This systematic review aimed to investigate the role of the C-X3-C motif ligand 1/chemokine receptor 1 C-X3-C motif (CX3CL1/CX3CR1) axis in the pathogenesis of periodontitis. Furthermore, as a secondary objective, we determine whether the CX3CL1/CX3CR1 axis could be considered complementary to clinical parameters to distinguish between periodontitis and rheumatoid arthritis (RA) and/or systemically healthy subjects. METHODS: The protocol used for this review was registered in OSF (10.17605/OSF.IO/KU8FJ). This study was designed following Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Records were identified using different search engines (PubMed/MEDLINE, Scopus, Science Direct, and Web of Science) from August 10, 2006, to September 15, 2023. The observational studies on human subjects diagnosed with periodontitis and RA and/or systemically healthy were selected to analyze CX3CL1 and CX3CR1 biomarkers. The methodological validity of the selected articles was assessed using NIH. RESULTS: Six articles were included. Biological samples (gingival crevicular fluid [GCF], saliva, gingival tissue biopsies, serum) from 379 subjects (n = 275 exposure group and n = 104 control group) were analyzed. Higher CX3CL1 and CX3CR1 chemokine levels were found in subjects with periodontitis and RA compared with periodontal and systemically healthy subjects. CONCLUSION: Very few studies highlight the role of the CX3CL1/CX3CR1 axis in the pathogenesis of periodontitis; however, increased levels of these chemokines are observed in different biological samples (GCF, gingival tissue, saliva, and serum) from subjects with periodontitis and RA compared with their healthy controls. Future studies should focus on long-term follow-up of subjects and monitoring changes in cytokine levels before and after periodontal therapy to deduce an appropriate interval in health and disease conditions.

Asunto(s)

RESUMEN

Cyrene, a green bioderived solvent from waste cellulose, was applied to the synthesis of novel α-acyloxyamide derivatives through a Passerini-3CR with carboxylic acids and isocyanides with good yields and diastereoselectivities under mild conditions. Cyrene showed exceptionally high reactivity and the degree of diastereoselection was dependent mostly on the isocyanide. DFT calculations as well as the experimental findings indicated that both kinetic and thermodynamic effects might explain the results.

Asunto(s)

RESUMEN

The internal topography of the root canal is complex, especially for the permanent molar's mesial root. In response to such issues, improved irrigation techniques have been created, which use laser pulses to agitate fluids and improve microbial deposit removal. Objective: To assess the effectiveness of the Er,Cr:YSGG laser with a wavelength of 2,780 nm via photon-induced photoacoustic streaming (PIPS) protocol which agitated of 2% chlorohexidine (CHX) in removing mature Enterococcus faecalis (E. faecalis) biofilm in root canal systems of lower molars. Material and Methods: The mesial roots of lower first and second molars were separated and inoculated with E. faecalis bacterial suspension for 30 days. The roots were irrigated with CHX, some of them were agitated with a passive ultrasonic device (PUI), while the other roots were agitated by an Er,Cr:YSGG laser in PIPS at 60 µs/pulse, 5 Hz, (0.25, 0.5, 0.75, and 1) W. An atomic force microscope (AFM) was used as a new method to get the results in the isthmus area; the obtained results from each group were compared with each other. Results: Based on the AFM and SEM analyses, laser and ultrasonic activation groups showed higher antimicrobial efficacy than the conventional syringe irrigation group (P<0.05). Conclusion: Based on the investigation's findings, the activation of 2% CHX solution by Er,Cr:YSGG laser in PIPS and PUI offers better mature bacterial biofilm removal in the mesial root of lower human molars than the same irrigant with the SI technique (AU)

A topografia interna do canal radicular é complexa, especialmente para a raiz mesial do molar permanente. Em resposta a esses problemas, foram criadas técnicas aprimoradas de irrigação, que utilizam pulsos de laser para agitar fluidos e melhorar a remoção de depósitos microbianos. Objetivo: Avaliar a eficácia do laser Er,Cr:YSGG com comprimento de onda de 2.780 nm via protocolo de streaming fotoacústico induzido por fótons (PIPS) que agitou clorohexidina a 2% (CHX) na remoção de Enterococcus faecalis maduro (E. faecalis) biofilme em sistemas de canais radiculares de molares inferiores. Material e Métodos: As raízes mesiais de 28 primeiros e segundos molares inferiores foram separadas e inoculadas com suspensão bacteriana de E. faecalis por 30 dias. As raízes foram irrigadas com CHX, sendo algumas delas agitadas com aparelho ultrassônico passivo (PUI), enquanto as demais raízes foram agitadas com laser Er,Cr:YSGG em PIPS a 60 µs/pulso, 5 Hz (0,25, 0,5, 0,75 e 1) W. Um microscópio de força atômica (AFM) foi utilizado como um novo método para obter os resultados na área do istmo; os resultados obtidos de cada grupo foram comparados entre si. Resultados: Com base nas análises de AFM e SEM, os grupos de ativação por laser e ultrassom apresentaram maior eficácia antimicrobiana do que o grupo de irrigação com seringa convencional (P<0.05). Conclusão: Com base nos achados da investigação, a ativação da solução de CHX a 2% pelo laser Er,Cr:YSGG em PIPS a (60 µs/pulso, 5 Hz, 0,75 W) oferece melhor remoção de biofilme (AU)

Asunto(s)

RESUMEN

Abstract Oral soft tissue lesions require a precise diagnosis by oral biopsy with the ability to recognize these lesions within histopathological levels, so the instrument used for the incisions should be safe and cause little to no harm to the surrounding tissue. Objective This study compared a dual-wavelength diode laser and an Er, Cr:YSGG laser in oral soft tissue incisions to determine the most effective and safest laser system at the histopathological level. Methodology The (810 and 980 nm) dual-wavelength diode laser was used at 1.5 W and 2.5 W (CW) power settings, and the (2780 nm) Er, Cr:YSGG laser was used at 2.5 W and 3.5 W (PW) power settings. Both laser systems were used to incise the tissues of freshly dissected sheep tongue pieces to obtain the following histopathological criteria: epithelial tissue changes, connective tissue changes, and lateral thermal damage extent by optical microscopy. Results The epithelial and connective tissue damage scores were significantly higher in the dual-wavelength diode laser groups than in the Er, Cr:YSGG laser groups (P<0.001), and there was a significant difference between some groups. The extent of lateral thermal damage was also significantly higher in the diode laser groups than in the Er, Cr: YSGG laser groups (P<0.001), and there was a significant difference between groups. Group 2 (2.5 W) of the diode laser was the highest for all three criteria, while group 3 (2.5 W) of the Er, Cr:YSGG laser was the lowest. Conclusion The Er, Cr:YSGG laser with an output power of 2.5 W is, histologically, the most effective and safest laser for oral soft tissue incision. The dual-wavelength diode laser causes more damage than the Er, Cr:YSGG laser, but it can be used with a low output power and 1 mm safety distance in excisional biopsy.

RESUMEN

Objective: The aim of this study is to identify the shear bond strength of rebonded CAD/CAM laminates made of lithium disilicate or feldspathic ceramics after debonding using Er,Cr:YSGG lasers. Material and Methods:Eighty bovine teeth (N=80) were used as a bonding substrate, which were divided into four main groups (20 each) according to the ceramic material and cement-curing mode used as follows: Group AL: lithium disilicate (IPS E.max) with light-cured resin cement, Group AD: lithium disilicate (IPS E.max) with dual-cured resin cement, Group BL: feldspathic porcelain (VITA MARK II) with light-cured resin cement, and Group BD: feldspathic porcelain (VITA MARK II) with dual-cured resin cement. Half the number of each subgroup (n=10/subdivisions) were tested for their shear bond strength without debonding, while the other half of the specimens were tested after Er,Cr:YSGG laser debonding and rebonding. A three-way ANOVA test was used to study the effect of ceramic and curing on shear bond strength. Bonferroni's post-hoc test was used for pairwise comparisons when the ANOVA test was significant. Results: After rebonding and using the light-cure mode, there was no statistically significant difference between the mean shear bond strength of the two ceramics (P-value = 0.065). However, after rebonding and using the dual-cured mode, E.max showed significantly lower shear bond strength than VITA (P-value < 0.001). Conclusion: Ceramic type, the cement's curing mode, and rebonding after laser irradiation all had a significant effect on the mean shear bond strength (AU)

Objetivo: Identificar a resistência de cisalhamento de laminados CAD/CAM recolados, feitos de cerâmica de disilicato de lítio ou feldspática, após descolamento utilizando lasers Er,Cr:YSGG. Material e Métodos: Oitenta dentes bovinos (N=80) foram utilizados como substrato de colagem, divididos em quatro grupos principais (20 cada) de acordo com o material cerâmico e o modo de cura do cimento utilizado da seguinte forma: Grupo AL: disilicato de lítio (IPS E.max) com cimento resinoso fotopolimerizável, Grupo AD: disilicato de lítio (IPS E.max) com cimento resinoso de dupla cura, Grupo BL: porcelana feldspática (VITA MARK II) com cimento resinoso fotopolimerizável, e Grupo BD: porcelana feldspática (VITA MARK II) com cimento resinoso de dupla cura. Metade do número de cada subgrupo (n=10/subdivisões) foi testada quanto à resistência de cisalhamento sem descolamento, enquanto a outra metade dos espécimes foi testada após descolamento e recolagem a laser Er,Cr:YSGG. Um teste ANOVA de três vias foi usado para estudar o efeito da cerâmica e da cura na resistência de cisalhamento. O teste post-hoc de Bonferroni foi usado para comparações pareadas quando o teste ANOVA foi significativo. Resultados: Após a recolagem e usando o modo de fotopolimerização, não houve diferença estatisticamente significativa entre a resistência de cisalhamento média das duas cerâmicas (valor de P = 0,065). No entanto, após a recolagem e usando o modo de dupla cura, o E.max apresentou resistência de cisalhamento significativamente menor que o VITA (valor de P < 0,001). Conclusão: O tipo de cerâmica, o modo de cura do cimento e a recolagem após irradiação a laser tiveram efeito significativo na resistência de cisalhamento média (AU)

Asunto(s)

RESUMEN

L-Amino acid oxidase (LAAO) is an enzyme found in snake venom that has multifaceted effects, including the generation of hydrogen peroxide (H2O2) during oxidative reactions, leading to various biological and pharmacological outcomes such as apoptosis, cytotoxicity, modulation of platelet aggregation, hemorrhage, and neutrophil activation. Human neutrophils respond to LAAO by enhancing chemotaxis, and phagocytosis, and releasing reactive oxygen species (ROS) and pro-inflammatory mediators. Exosomes cellular nanovesicles play vital roles in intercellular communication, including immune responses. This study investigates the impact of Calloselasma rhodostoma snake venom-derived LAAO (Cr-LAAO) on human neutrophil exosome release, including activation patterns, exosome formation, and content. Neutrophils isolated from healthy donors were stimulated with Cr-LAAO (100 µg/mL) for 3 h, followed by exosome isolation and analysis. Results show that Cr-LAAO induces the release of exosomes with distinct protein content compared to the negative control. Proteomic analysis reveals proteins related to the regulation of immune responses and blood coagulation. This study uncovers Cr-LAAO's ability to activate human neutrophils, leading to exosome release and facilitating intercellular communication, offering insights into potential therapeutic approaches for inflammatory and immunological disorders.

Asunto(s)

RESUMEN

The chemokine fractalkine (FKN, CX3CL1), a member of the CX3C subfamily, contributes to neuron-glia interaction and the regulation of microglial cell activation. Fractalkine is expressed by neurons as a membrane-bound protein (mCX3CL1) that can be cleaved by extracellular proteases generating several sCX3CL1 forms. sCX3CL1, containing the chemokine domain, and mCX3CL1 have high affinity by their unique receptor (CX3CR1) which, physiologically, is only found in microglia, a resident immune cell of the CNS. The activation of CX3CR1contributes to survival and maturation of the neural network during development, glutamatergic synaptic transmission, synaptic plasticity, cognition, neuropathic pain, and inflammatory regulation in the adult brain. Indeed, the various CX3CL1 forms appear in some cases to serve an anti-inflammatory role of microglia, whereas in others, they have a pro-inflammatory role, aggravating neurological disorders. In the last decade, evidence points to the fact that sCX3CL1 and mCX3CL1 exhibit selective and differential effects on their targets. Thus, the balance in their level and activity will impact on neuron-microglia interaction. This review is focused on the description of factors determining the emergence of distinct fractalkine forms, their age-dependent changes, and how they contribute to neuroinflammation and neurodegenerative diseases. Changes in the balance among various fractalkine forms may be one of the mechanisms on which converge aging, chronic CNS inflammation, and neurodegeneration.

RESUMEN

The ß2 integrin CD11b/CD18, also known as complement receptor 3 (CR3), and the moonlighting protein aminopeptidase N (CD13), are two myeloid immune receptors with overlapping activities: adhesion, migration, phagocytosis of opsonized particles, and respiratory burst induction. Given their common functions, shared physical location, and the fact that some receptors can activate a selection of integrins, we hypothesized that CD13 could induce CR3 activation through an inside-out signaling mechanism and possibly have an influence on its membrane expression. We revealed that crosslinking CD13 on the surface of human macrophages not only activates CR3 but also influences its membrane expression. Both phenomena are affected by inhibitors of Src, PLCγ, Syk, and actin polymerization. Additionally, after only 10 min at 37 °C, cells with crosslinked CD13 start secreting pro-inflammatory cytokines like interferons type 1 and 2, IL-12p70, and IL-17a. We integrated our data with a bioinformatic analysis to confirm the connection between these receptors and to suggest the signaling cascade linking them. Our findings expand the list of features of CD13 by adding the activation of a different receptor via inside-out signaling. This opens the possibility of studying the joint contribution of CD13 and CR3 in contexts where either receptor has a recognized role, such as the progression of some leukemias.

Asunto(s)