Silicosis is an occupational lung disease, characterized by irreversible and progressive fibrosis. Silica exposure leads to intense lung inflammation, reactive oxygen production, and extracellular ...ATP (eATP) release by macrophages. The P2X7 purinergic receptor is thought to be an important immunomodulator that responds to eATP in sites of inflammation and tissue damage. The present study investigates the role of P2X7 receptor in a murine model of silicosis. To that end wild-type (C57BL/6) and P2X7 receptor knockout mice received intratracheal injection of saline or silica particles. After 14 days, changes in lung mechanics were determined by the end-inflation occlusion method. Bronchoalveolar lavage and flow cytometry analyzes were performed. Lungs were harvested for histological and immunochemistry analysis of fibers content, inflammatory infiltration, apoptosis, as well as cytokine and oxidative stress expression. Silica particle effects on lung alveolar macrophages and fibroblasts were also evaluated in cell line cultures. Phagocytosis assay was performed in peritoneal macrophages. Silica exposure increased lung mechanical parameters in wild-type but not in P2X7 knockout mice. Inflammatory cell infiltration and collagen deposition in lung parenchyma, apoptosis, TGF-β and NF-κB activation, as well as nitric oxide, reactive oxygen species (ROS) and IL-1β secretion were higher in wild-type than knockout silica-exposed mice. In vitro studies suggested that P2X7 receptor participates in silica particle phagocytosis, IL-1β secretion, as well as reactive oxygen species and nitric oxide production. In conclusion, our data showed a significant role for P2X7 receptor in silica-induced lung changes, modulating lung inflammatory, fibrotic, and functional changes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Genomic surveillance represents a strategy to understanding the evolutionary mechanisms, transmission, and infectivity of different SARS-CoV-2 variants. We evaluated 603 individuals positive for ...SARS-CoV-2 from 34 municipalities of Rondônia between December 2021 to December 2022. Nasopharyngeal samples were collected, RNA was extracted and screened using RT-qPCR for VOCs. RNA of the samples were sequenced and further analyzed for phylogeny, mutations, and lineages, totaling 96.19% of samples positive for Omicron VOC in this cohort. We observed that most individuals had at least two doses, however 18.97% were not vaccinated with any dose. 554 sequences were amenable to analysis for alignment and phylogenetic characterization; this group corresponded to the 27 subvariants of the Omicron VOC; a total of 100 mutations were identified, 48% of which were found in the S gene. In conclusion, the data demonstrated the rapid spread and persistence of Omicron VOC in Rondônia during the 12-month study period. Although high frequency of mutations was found in the analyzed samples, there were no individuals with a severe clinical profile, demonstrating that vaccination had a positive effect in those cases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Fungi are a rich source of bioactive compounds. Fungal cocultivation is a method of potentiating chemical interactions and, consequently, increasing bioactive molecule production. In this study, we ...evaluated the bactericidal, antiprotozoal, and cathepsin V inhibition activities of extracts from axenic cultures of 6 fungi (
, and
) that infest tropical fruits and 57 extracts obtained by their cocultivation. Our results reveal that fungal cocultivation enhances the biological activity of the samples, since all extracts that were active on Gram-positive bacteria, Gram-negative bacteria,
, and
were obtained from cocultivation. Bacterial growth is either totally or partially inhibited by 46% of the extracts. Two extracts containing mainly fusaric and 9,10-dehydrofusaric acids were particularly active. The presence of the fungus
in co-cultures that give rise to extracts with the highest activities against
. An axenic culture gave rise to the most active extract for the inhibition of cathepsin V; however, other coculture extracts also exhibited activity toward this biological target. Therefore, the results of the biological activities indicate that fungal cocultivation increased the biological potential of samples, likely due to the hostile and competitive environment that pushes microorganisms to produce substances important for defense and allows access to metabolic routes then silenced in milder cultivation conditions.
Many microorganisms from various sources may be present in ejaculates of bulls. This study identified and isolated bacteria from bull sperm samples in a commercial stud and evaluated their resistance ...to antibiotics. The number of colony‐forming units was determined in semen samples collected at distinct steps during freezing and thawing. The minimum inhibitory concentration and the minimum bactericidal concentration were determined for four antibiotics commonly used in commercial studs. A total of 135 microorganisms from 25 genera were isolated. After a sensitivity test, all evaluated microorganisms (n = 55) were resistant to penicillin and most of them were resistant to tylosin and lincomycin (n = 54). Resistance to all tested antibiotics was observed in 22% of all isolates, whereas only 3.9% of the isolates were inhibited by the tested antibiotics at the concentrations recommended by the international legislation. As the isolated microorganisms presented high resistance to frequently used antibiotics, sensitivity tests should be periodically conducted in commercial bull semen studs to prevent the use of contaminated semen in artificial insemination.
Binding between bovine serum albumin (BSA) and a plumeran indole alkaloid (PIA) isolated from the stem bark of Aspidosperma cylindrocarpon (Apocynaceae) was studied by spectroscopic techniques ...(UV-Vis absorption, circular dichroism, steady state and time-resolved fluorescence), combined with molecular docking. Steady state and time resolved fluorescence data revealed that PIA can quench the BSA fluorescence via a static mechanism: energy transfer from BSA to PIA occurs with high probability. The binding is strong (Kb ca. 105-106 L mol-1), spontaneous (ΔG° ca. -35.7 kJ mol-1 at 310 K) and entropy-driven (ΔS° = 0.146 kJ mol-1 K-1). There is just one main binding site (n ca. 1) for the BSA:PIA interaction and the α-helix content of the albumin does not suffer significant perturbation upon PIA binding. Molecular docking results suggest site I as the main binding site to PIA, which is able to interact with the Trp-212, Arg-217, Val-342 and Pro-446 residues.
Leishmania amazonensis
is the etiologic agent of cutaneous leishmaniasis, an immune-driven disease causing a range of clinical symptoms. Infections caused by
L. amazonensis
suppress the activation ...and function of immune cells, including macrophages, dendritic cells, and CD4
+
T cells. In this study, we analyzed the course of infection as well as the leishmanicidal effect of intralesional UTP treatment in
L. amazonensis
-infected BALB/c mice
.
We found that UTP treatment reduced the parasitic load in both footpad and lymph node sites of infection. UTP also boosted Th1 immune responses, increasing CD4
+
T cell recruitment and production of IFN-γ, IL-1β, IL-12, and TNF-α. In addition, the role of UTP during innate immune response against
L. amazonensis
was evaluated using the air pouch model. We observed that UTP augmented neutrophil chemoattraction and activated microbicidal mechanisms, including ROS production. In conclusion, our data suggested an important role for this physiological nucleotide in controlling
L. amazonensis
infection, and its possible use as a therapeutic agent for shifting immune responses to Th1 and increasing host resistance against
L. amazonensis
infection.
The use of bioprocess to convert low valued biomass or agroindustrial byproducts into high-value chemicals is an emerging area. However, laboratories usually use outdated analytical techniques to ...identify bioproducts, losing valuable information, such as the identification of unexpected compounds. In this work, we presented a successful systematic and modern analytical approach based on direct infusion mass spectrometry (DIMS) for an automated high-throughput screening of untargeted compounds from glycerin bioconversion process. We describe advantages of DIMS and its combined application with chemometrics towards an untargeted metabolomics approach to analyze several samples in a short time (11 samples per h). Three batches with 34 samples from the bioconversion of glycerin using several filamentous fungi strains were analyzed. Batch 347 was selected as promising, since high value chemicals, such as amide, phenolic and acid compounds, were identified. The platform presented was fast, robust, and versatile, then it could be applied to different bioprocesses.
Leishmania amazonensis is the etiologic agent of cutaneous leishmaniasis, an immune-driven disease causing a range of clinical symptoms. Infections caused by L. amazonensis suppress the activation ...and function of immune cells, including macrophages, dendritic cells, and CD4
T cells. In this study, we analyzed the course of infection as well as the leishmanicidal effect of intralesional UTP treatment in L. amazonensis-infected BALB/c mice. We found that UTP treatment reduced the parasitic load in both footpad and lymph node sites of infection. UTP also boosted Th1 immune responses, increasing CD4
T cell recruitment and production of IFN-γ, IL-1β, IL-12, and TNF-α. In addition, the role of UTP during innate immune response against L. amazonensis was evaluated using the air pouch model. We observed that UTP augmented neutrophil chemoattraction and activated microbicidal mechanisms, including ROS production. In conclusion, our data suggested an important role for this physiological nucleotide in controlling L. amazonensis infection, and its possible use as a therapeutic agent for shifting immune responses to Th1 and increasing host resistance against L. amazonensis infection.
The efficiency of Moringa oleifera (MO) seeds as a natural coagulant in the coagulation/flocculation process, followed by nanofiltration (NF) for the removal of cyanobacterial cells and cyanotoxins ...is investigated. "Synthetic water" prepared for the tests comprised de-ionized water with an inoculum of microcystis protocystis cells to obtain turbidity within the 50-450 NTU range. Methodology followed two steps: 1) coagulation/flocculation/sedimentation (C/F/S) process using MO extracted in a saline solution of potassium chloride (KCl-1M) as coagulant to determine best dosage; 2) nanofiltration process using NF-90 and NF-270 membranes, with slightly different characteristics. A 5 bar working pressure was applied. Physical, chemical (color, turbidity and pH) and microbiological (cyanobacterial cells count and microcystin concentration) parameters were analyzed in all samples. Current study shows that, as a natural coagulant, MO seeds provided satisfactory results in M. protocystis, color and turbidity removal and did not cause cell lysis. NF completely removed cyanobacterial cells and microcystins (100%) from M. protocystis (within the quantification limits). Results show that C/F/S+NF sequence is a safe barrier against M.protocystis and microcystins in drinking water.
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