Aim
This randomized placebo‐controlled clinical trial evaluated the effect of Bifidobacterium animalis subsp. lactis (B. lactis) HN019‐containing probiotic lozenges as adjuvant to scaling and root ...planing (SRP) in patients with generalized chronic periodontitis.
Materials and Methods
Forty‐one chronic periodontitis patients were recruited and monitored clinically, immunologically, and microbiologically at baseline (before SRP) and 30 and 90 days after SRP. All patients were randomly assigned to a Test (SRP + Probiotic, n = 20) or Control (SRP + Placebo, n = 21) group. The probiotic lozenges were used twice a day for 30 days. The data were statistically analysed.
Results
The Test group presented a decrease in probing pocket depth and a clinical attachment gain significantly higher than those of the Control group at 90 days. The Test group also demonstrated significantly fewer periodontal pathogens of red and orange complexes, as well as lower proinflammatory cytokine levels when compared to the Control group. Only the Test group showed an increase in the number of B. lactis HN019 DNA copies on subgingival biofilm at 30 and 90 days.
Conclusion
The use of B. lactis HN019 as an adjunct to SRP promotes additional clinical, microbiological, and immunological benefits in the treatment of chronic periodontitis (NCT03408548).
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BFBNIB, CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Toxoplasmosis affects one-third of the human population worldwide. Humans are accidental hosts and are infected after consumption of undercooked meat and water contaminated with Toxoplasma gondii ...cysts and oocysts, respectively. Neutrophils have been shown to participate in the control of T. gondii infection in mice through a variety of effector mechanisms, such as reactive oxygen species (ROS) and neutrophil extracellular trap (NET) formation. However, few studies have demonstrated the role of neutrophils in individuals naturally infected with T. gondii. In the current study, we evaluated the activation status of neutrophils in individuals with acute or chronic toxoplasmosis and determined the role of T. gondii-induced NET formation in the amplification of the innate and adaptive immune responses. We observed that neutrophils are highly activated during acute infection through increased expression of CD66b. Moreover, neutrophils from healthy donors (HDs) cocultured with tachyzoites produced ROS and formed NETs, with the latter being dependent on glycolysis, succinate dehydrogenase, gasdermin D, and neutrophil elastase. Furthermore, we observed elevated levels of the chemokines (CXC motif) CXCL8 and (CC motif) CCL4 ligands in plasma from patients with acute toxoplasmosis and production by neutrophils from HDs exposed to
. Finally, we showed that T. gondii-induced NETs activate neutrophils and promote the recruitment of autologous CD4
T cells and the production of interferon gamma (IFN-γ), tumor necrosis factor (TNF), interleukin 6 (IL-6), IL-17, and IL-10 by peripheral blood mononuclear cells. In conclusion, we demonstrated that T. gondii activates neutrophils and promotes the release of NETs, which amplify human innate and adaptive immune responses.
Approximately one-third of the human population is estimated to be chronically infected with the obligate intracellular parasite Toxoplasma gondii. Humans are accidental hosts that are infected with T. gondii after consumption of undercooked meat or contaminated water. Neutrophils have been shown to control T. gondii growth by different mechanisms, including neutrophil extracellular traps (NETs). In the current study, we observed that neutrophils are highly activated during acute toxoplasmosis. We also determined that T. gondii-induced NETs are dependent on the energetic profile of neutrophils as well as the production of ROS and gasdermin D (GSDMD) cleavage. In addition, we showed that T. gondii-induced NETs activate neutrophils, promote the recruitment of autologous CD4
T cells, and induce the production of cytokines by peripheral blood mononuclear cells, amplifying the innate and adaptive immune responses.
Arsenic is an environmental toxicant known to be a carcinogen and endocrine disruptor. Maternal exposure to arsenic has been associated with fetus malformation and reproductive disorders in male ...offspring. However, it is unclear the extent to which those effects remain during postnatal development and adulthood. Therefore, this study aimed to investigate the long‐term effects of prenatal arsenic exposure on reproductive parameters of male offspring at peripubertal and adult periods. Pregnant female Wistar rats were exposed to 0 or 10 mg/L sodium arsenite in drinking water from gestational day 1 (GD 1) until GD 21 and male pups were analyzed at postnatal day 44 (PND 44) and PND 70. We observed that some reproductive parameters were affected differently by arsenic exposure at each age evaluated. The body and reproductive organs weights, as well as testicular and epididymal morphology were strongly affected in peripubertal animals and recovered at adult period. On the other hand, the antioxidant genes expression (SOD1, SOD2, CAT and GSTK1) and the endogenous antioxidant system were affected in the testes and epididymides from both peripubertal and adult rats. Finally, an impairment in daily sperm production and in sperm parameters was observed in adult animals. Taken together, our findings show that prenatal arsenic exposure affected reproductive parameters of peripubertal and adult male rats mainly due to oxidative stress. Collectively, those alterations may be affecting fertility potential of adult animals.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Introduction
Irinotecan (CPT-11) is an inhibitor of DNA topoisomerase I and is clinically effective against several cancers. A major toxic effect of CPT-11 is delayed diarrhea; however, the exact ...mechanism by which the drug induces diarrhea has not been established.
Purpose
Elucidate the mechanisms of induction of delayed diarrhea and determine the effects of the cytokine production inhibitor pentoxifylline (PTX) and thalidomide (TLD) in the experimental model of intestinal mucositis, induced by CPT-11.
Materials and methods
Intestinal mucositis was induced in male
Swiss
mice by intraperitoneal administration of CPT-11 (75 mg/kg) daily for 4 days. Animals received subcutaneous PTX (1.7, 5 and 15 mg/kg) or TLD (15, 30, 60 mg/kg) or 0.5 ml of saline daily for 5 and 7 days, starting 1 day before the first CPT-11 injection. The incidence of delayed diarrhea was monitored by scores and the animals were sacrificed on the 5th and 7th experimental day for histological analysis, immunohistochemistry for TNF-α and assay of myeloperoxidase (MPO) activity, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and KC ELISA.
Results
CPT-11 caused significant diarrhea, histopathological alterations (inflammatory cell infiltration, loss of crypt architecture and villus shortening) and increased intestinal tissue MPO activity, TNF-α, IL-1β and KC level and TNF-α immuno-staining. PTX inhibited delayed diarrhea of mice submitted to intestinal mucositis and reduced histopathological damage, intestinal MPO activity, tissue level of TNF-α, IL-1β and KC and TNF-α immuno-staining. TLD significantly reduced the lesions induced by CPT-11 in intestinal mucosa, decreased MPO activity, TNF-α tissue level and TNF-α immuno-staining, but did not reduce the severity of diarrhea.
Conclusion
These results suggest an important role of TNF-α, IL-1β and KC in the pathogenesis of intestinal mucositis induced by CPT-11.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Multiple infectious diseases lead to impaired lung function. Revealing the cellular mechanisms involved in this impairment is crucial for the understanding of how the lungs shift from a physiologic ...to a pathologic state in each specific condition. In this context, we explored the pathogenesis of Paracoccidioidomycosis, which affects pulmonary functioning. The presence of cells expressing Nestin-GFP has been reported in different tissues, and their roles as tissue-specific progenitors have been stablished in particular organs. Here, we explored how Nestin-GFP
cells are affected after lung infection by Paracoccidioides brasiliensis, a model of lung granulomatous inflammation with fibrotic outcome. We used Nestin-GFP transgenic mice, parabiosis surgery, confocal microscopy and flow cytometry to investigate the participation of Nestin-GFP
cells in Paracoccidioides brasiliensis pathogenesis. We revealed that these cells increase in the lungs post-Paracoccidioides brasiliensis infection, accumulating around granulomas. This increase was due mainly to Nestin-GPF
cells derived from the blood circulation, not associated to blood vessels, that co-express markers suggestive of hematopoietic cells (Sca-1, CD45 and CXCR4). Therefore, our findings suggest that circulating Nestin-GFP
cells participate in the Paracoccidioides brasiliensis pathogenesis in the lungs.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Diversity found in Neotropical freshwater fish is remarkable. It can even hinder a proper delimitation of many species, with the wolf fish
(Teleostei, Characiformes) being a notable example. This ...nominal species shows remarkable intra-specific variation, with extensive karyotype diversity found among populations in terms of different diploid chromosome numbers (2
), karyotype compositions and sex chromosome systems. Here, we analyzed three distinct populations (one of them cytogenetically investigated for the first time) that differed in terms of their chromosomal features (termed karyomorphs) and by the presence or absence of heteromorphic sex chromosomes. We combined cytogenetics with genomic approaches to investigate how the evolution of multiple sex chromosomes together with allopatry is linked to genetic diversity and speciation. The results indicated the presence of high genetic differentiation among populations both from cytogenetic and genomic aspects, with long-distance allopatry potentially being the main agent of genetic divergence. One population showed a neo-X
X
Y sexual chromosome system and we hypothesize that this system is associated with enhanced inter-population genetic differentiation which could have potentially accelerated speciation compared to the effect of allopatry alone.
Abstract
The regulation of the kallikrein-kinin system is an important mechanism controlling vasodilation and promoting inflammation. We aimed to investigate the role of Toll-like receptor 2 (TLR2) ...in regulating kinin B
1
and B
2
receptor expression in human gingival fibroblasts and in mouse gingiva. Both
P. gingivalis
LPS and the synthetic TLR2 agonist Pam
2
CSK
4
increased kinin receptor transcripts. Silencing of TLR2, but not of TLR4, inhibited the induction of kinin receptor transcripts by both
P. gingivalis
LPS and Pam
2
CSK
4
. Human gingival fibroblasts (HGF) exposed to Pam
2
CSK
4
increased binding sites for bradykinin (BK, B
2
receptor agonist) and des-Arg
10
-Lys-bradykinin (DALBK, B
1
receptor agonist). Pre-treatment of HGF for 24 h with Pam
2
CSK
4
resulted in increased PGE
2
release in response to BK and DALBK. The increase of B1 and B2 receptor transcripts by
P. gingivalis
LPS was not blocked by IL-1β neutralizing antibody; TNF-α blocking antibody did not affect B
1
receptor up-regulation, but partially blocked increase of B
2
receptor mRNA. Injection of
P. gingivalis
LPS in mouse gingiva induced an increase of B
1
and B
2
receptor mRNA. These data show that activation of TLR2 in human gingival fibroblasts as well as in mouse gingival tissue leads to increase of B
1
and B
2
receptor mRNA and protein.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Allopatry is generally considered to be one of the main contributors to the remarkable Neotropical biodiversity. However, the role of chromosomal rearrangements including neo-sex chromosomes for ...genetic diversity is still poorly investigated and understood. Here, we assess the genetic divergence in five
species using population genomics and combined the results with previously obtained cytogenetic data, highlighting that molecular genetic diversity is consistent with their chromosomal features. The results of a principal coordinate analysis (PCoA) indicated a clear difference among all species while showing a closer relationship of the ones located in the same geographical region. This was also observed in genetic structure analyses that only grouped
and
, which were also recovered as sister species in a species tree analysis. We observed a contradictory result for the relationships among the three species from the Amazon basin, as the phylogenetic tree suggested
and
as sister species, while the PCoA showed a high genetic difference between
and all other species. These results suggest a potential role of sex-related chromosomal rearrangements as reproductive barriers between these species.
Background: This study evaluates effects of topical administration of probiotic bacteria of the genus Bifidobacterium on experimental periodontitis (EP) in rats.
Methods: Thirty‐two rats were divided ...into groups C (control; without EP), EP (EP only), C‐HN019 (control+probiotic), and EP‐HN019 (EP+probiotic). On day 0 of the experiment, animals of groups EP and EP‐HN019 received cotton ligatures around mandibular first molars (MFMs). In groups C‐HN019 and EP‐HN019, 1 mL of suspensions containing Bifidobacterium animalis subsp. lactis (B. lactis) HN019 was topically administered in the subgingival region of MFMs on days 0, 3, and 7. In groups C and EP, topical administrations were performed using a sham suspension (without probiotic). All animals were euthanized at day 14. Gingival tissue, hemimandibles, and oral biofilm were collected. Data were statistically analyzed (P <0.05).
Results: Group EP presented greater bone porosity, trabecular separation, and connective tissue attachment loss (CTAL) as well as reduced bone volume than all other groups (P <0.05). In group EP‐HN019, there were greater proportions of Actinomyces and Streptococcus‐like species and lower proportions of Veillonella parvula, Capnocytophaga sputigena, Eikenella corrodens, and Prevotella intermedia‐like species than group EP. Group EP‐HN019 presented greater expressions of osteoprotegerin and β‐defensins than group EP (P <0.05). Group EP presented greater levels of interleukin‐1β and receptor activator of nuclear factor‐kappa B ligand than group EP‐HN019 (P <0.05).
Conclusion: Topical use of B. lactis HN019 promotes a protective effect against alveolar bone loss and CTALs attributable to EP in rats, modifying immunoinflammatory and microbiologic parameters.
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BFBNIB, CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The combination of chiral supported‐organocatalysts and flow chemistry promotes the sustainable production of enantioenriched compounds providing a very powerful tool for chemical and pharmaceutical ...industries. However, the rapid deactivation of these catalysts in heterogeneous asymmetric reactions has been limiting the expansion of the area. In this work we report for the first time the advantages of synthesizing, immobilizing, and using a silica‐supported organocatalyst under a complete continuous‐flow approach, showing the impact of this method on the morphology, structure and lifetime of the organocatalyst. The first generation MacMillan's organocatalyst was prepared from L‐phenylalanine and immobilized in silica through a carbamate linkage under batch and continuous‐flow conditions. We also evaluated the performance of both batch and continuous‐flow organocatalysts in the Diels‐Alder reaction for proof of concept.
Flow to prevent degradation: A major issue of silica‐supported organocatalysts is the degradation of the solid material and the erosion of the matrix properties during its immobilization and usage in batch. In this work, we report for the first time, the advantages of a complete continuous‐flow approach towards the synthesis, immobilization and use of MacMillan's silica‐supported organocatalyst.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
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