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1.
Microorganisms ; 12(6)2024 May 24.
Article in English | MEDLINE | ID: mdl-38930439

ABSTRACT

Periodontitis is a destructive inflammatory response triggered by dysbiosis. Lactobacillus acidophilus LA5 (LA5) may impair microbial colonization and alter the host. Thus, we evaluated the effect of LA5 on alveolar bone loss in a periodontitis murine model and investigated its effect on the oral and gut microbiomes. Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, and Streptococcus gordonii were inoculated in C57BL/6 mice (P+), with LA5 (L+). SHAM infected controls (P- and/or L- groups) were also evaluated. After 45 days, alveolar bone loss in the maxilla and oral and gut microbiomes were determined. The administration of LA5 controlled the microbial consortium-induced alveolar bone loss. Periodontopathogens infection resulted in shifts in the oral and gut microbiomes consistent with dysbiosis, and LA5 reshaped these changes. The oral microbiome of P+L- group showed the increased abundance of Enterococaccea, Streptoccocaceae, Staphylococcaceae, Moraxellaceae, and Pseudomonadaceae, which were attenuated by the administration of LA5 to the infected group (P+L+). The administration of LA5 to otherwise non-infected mice resulted in the increased abundance of the superphylum Patescibacteria and the family Saccharamonadaceae in the gut. These data indicate L. acidophilus LA5 as a candidate probiotic for the control of periodontitis.

2.
Vet Surg ; 53(4): 769-775, 2024 May.
Article in English | MEDLINE | ID: mdl-38402631

ABSTRACT

OBJECTIVE: To report a case of unilateral lateral coronoid process fragmentation in a dog treated via lateral elbow arthroscopy portals. ANIMAL: A 9-month old male intact English Bulldog. STUDY DESIGN: Case report. METHODS: The dog presented with a history of intermittent right thoracic limb lameness. Orthopedic examination on presentation was unremarkable. Computed tomography of the right thoracic limb was pursued and revealed a mineralized focus along the lateral margin of the lateral coronoid process as well as sclerosis of the medial coronoid process and subtrochlear region of the ulna. Elbow arthroscopy was performed via a lateral approach and revealed chondromalacia of the entire lateral coronoid process. Abrasion arthroplasty of the lateral coronoid process was performed. RESULTS: Complete resolution of the lameness was achieved within two weeks of surgery. At 6 weeks postoperatively, the dog remained sound and a gradual return to normal activity was recommended. At the final follow up assessment, 5 months after surgery, no abnormalities were found on orthopedic examination and the owners reported excellent limb function with no observable lameness. CONCLUSION: Lateral coronoid disease can occur as a rare component of elbow dysplasia in dogs. Abrasion arthroplasty via lateral arthroscopic portals may have resulted in a successful outcome in this case and may form an effective treatment option for lateral coronoid disease in dogs.


Subject(s)
Arthroscopy , Dog Diseases , Dogs , Animals , Arthroscopy/veterinary , Arthroscopy/methods , Male , Dog Diseases/surgery , Lameness, Animal/surgery , Forelimb/surgery , Ulna/surgery
3.
Vet Radiol Ultrasound ; 65(2): 107-113, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38254308

ABSTRACT

The Orthopedic Foundation for Animals (OFA) radiographic grading system stands as a well-established benchmark for categorizing hip dysplasia in canines. Although more objective techniques to quantify early hip laxity in young dogs, such as the Norberg angle (NA) and distraction index (DI), have been documented, there is a scarcity of published studies that directly compare these radiographic measures. The primary objectives of this prospective, analytical study were to assess and compare the NA and DI measures with OFA grades within a cohort of dogs. Thirty dogs (57 hip joints) were evaluated, with a mean age of 5.4 ± 2.9 years and a mean body weight of 34.3 ± 7.1 kg. The discriminative power of hip dysplasia for DI and NA used OFA as a reference were compared by multivariate discriminant analysis test. Using the DI (≤0.3) 12 joints were classified as normal, using NA (≥105°) 24 joints and using OFA (≤3) 29. When comparing the discriminant power of NA with OFA resulting similar (P = .8324) with correct classifications of 81% using cross validation, however, the discriminant power of dysplasia of the DI resulted significantly greater (P = .0034) than OFA with correct classifications of only 59% using cross-validation, consequently it was possible determined that of 29 patients with OFA ≤ 3, 20 had DI > 0.3. These findings demonstrated that phenotypic healthy dogs according to OFA grading can present passive hip joint laxity, as demonstrated by radiographic evaluation with distraction. Furthermore, DI can contribute to the screening of CHD when evaluated in conjunction with OFA grading.


Subject(s)
Dog Diseases , Hip Dislocation , Hip Dysplasia, Canine , Joint Instability , Humans , Dogs , Animals , Hip Dysplasia, Canine/diagnostic imaging , Hip Dislocation/diagnostic imaging , Hip Dislocation/veterinary , Prospective Studies , Radiography , Hip Joint/diagnostic imaging , Joint Instability/diagnostic imaging , Joint Instability/veterinary , Dog Diseases/diagnostic imaging
4.
Cancers (Basel) ; 15(18)2023 Sep 12.
Article in English | MEDLINE | ID: mdl-37760494

ABSTRACT

Lung tumors frequently metastasize to the brain. Brain metastasis (BM) is common in advanced cases, and a major cause of patient morbidity and mortality. The precise molecular mechanisms governing BM are still unclear, in part attributed to the rarity of BM specimens. In this work, we compile a unique transcriptomic dataset encompassing RNA-seq, microarray, and single-cell analyses from BM samples obtained from patients with lung adenocarcinoma (LUAD). By integrating this comprehensive dataset, we aimed to enhance understanding of the molecular landscape of BM, thereby facilitating the identification of novel and efficient treatment strategies. We identified 102 genes with significantly deregulated expression levels in BM tissues, and discovered transcriptional alterations affecting the key driver 'hub' genes CD69 (a type II C-lectin receptor) and GZMA (Granzyme A), indicating an important role of the immune system in the development of BM from primary LUAD. Our study demonstrated a BM-specific gene expression pattern and revealed the presence of dendritic cells and neutrophils in BM, suggesting an immunosuppressive tumor microenvironment. These findings highlight key drivers of LUAD-BM that may yield therapeutic targets to improve patient outcomes.

5.
Int J Clin Pediatr Dent ; 16(Suppl 1): S27-S32, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37663206

ABSTRACT

Aim: This study evaluated the short-term clinical and microbiological performance of resin-modified glass ionomer cement (RM-GIC) cement containing chlorhexidine (CHX) for atraumatic restorative treatment (ART) in primary teeth. Materials and methods: The clinical trial was conducted in 36 children that received ART in primary molars either with GIC (group I, n = 18) or GIC containing 1.25% CHX (group II, n = 18). The survival rate of restorations was checked 7 days, 3, and 6 months after their application when saliva and biofilm were collected for microbiological assessment of mutans streptococci (MS) counts. Data were analyzed using the Kruskal-Wallis/Mann-Whitney U tests for clinical analysis and microbiological evaluations (p < 0.05). Results: The survival rate of restorations was similar comparing groups I with II. Microbiological analysis showed a significant reduction in MS levels 7 days after the treatment in both saliva and biofilm of children treated with RM-GIC containing CHX (group II); however, MS counts at 3 and 6 months did not differ from the initial counts. Conclusion: A total of 1.25% CHX improved the microbiological properties of GIC in the short term without impairing the clinical performance of ART restorations. Clinical significance: Glass ionomer cement (GIC) containing CHX could be an alternative in ART procedures with the objective of promoting an additional antimicrobial effect, which is interesting for children with high counts of MS during the initial phase of adaptation to dental treatment. How to cite this article: da Silva ME, de Sena MD, Colombo NH, et al. Short-term Clinical and Microbiological Performance of Resin-modified Glass Ionomer Cement Containing Chlorhexidine for Atraumatic Restorative Treatment. Int J Clin Pediatr Dent 2023;16(S-1):S27-S32.

6.
NPJ Aging ; 9(1): 21, 2023 Aug 24.
Article in English | MEDLINE | ID: mdl-37620330

ABSTRACT

Age is a significant risk factor for the coronavirus disease 2019 (COVID-19) severity due to immunosenescence and certain age-dependent medical conditions (e.g., obesity, cardiovascular disorder, and chronic respiratory disease). However, despite the well-known influence of age on autoantibody biology in health and disease, its impact on the risk of developing severe COVID-19 remains poorly explored. Here, we performed a cross-sectional study of autoantibodies directed against 58 targets associated with autoimmune diseases in 159 individuals with different COVID-19 severity (71 mild, 61 moderate, and 27 with severe symptoms) and 73 healthy controls. We found that the natural production of autoantibodies increases with age and is exacerbated by SARS-CoV-2 infection, mostly in severe COVID-19 patients. Multiple linear regression analysis showed that severe COVID-19 patients have a significant age-associated increase of autoantibody levels against 16 targets (e.g., amyloid ß peptide, ß catenin, cardiolipin, claudin, enteric nerve, fibulin, insulin receptor a, and platelet glycoprotein). Principal component analysis with spectrum decomposition and hierarchical clustering analysis based on these autoantibodies indicated an age-dependent stratification of severe COVID-19 patients. Random forest analysis ranked autoantibodies targeting cardiolipin, claudin, and platelet glycoprotein as the three most crucial autoantibodies for the stratification of severe COVID-19 patients ≥50 years of age. Follow-up analysis using binomial logistic regression found that anti-cardiolipin and anti-platelet glycoprotein autoantibodies significantly increased the likelihood of developing a severe COVID-19 phenotype with aging. These findings provide key insights to explain why aging increases the chance of developing more severe COVID-19 phenotypes.

7.
Preprint in English | medRxiv | ID: ppmedrxiv-22282902

ABSTRACT

Age is a significant risk factor for the coronavirus disease 2019 (COVID-19) outcomes due to immunosenescence and certain age-dependent medical conditions (e.g., obesity, cardiovascular disorder, diabetes, chronic respiratory disease). However, despite the well-known influence of age on autoantibody biology in health & disease, its impact on the risk of developing severe COVID-19 remains poorly explored. Here, we performed a cross-sectional study of autoantibodies directed against 58 targets associated with autoimmune diseases in 159 individuals with different COVID-19 outcomes (with 71 mild, 61 moderate, and 27 severe patients) and 73 healthy controls. We found that the natural production of autoantibodies increases with age and is exacerbated by SARS-CoV-2 infection, mostly in severe COVID-19 patients. Multivariate regression analysis showed that severe COVID-19 patients have a significant age-associated increase of autoantibody levels against 16 targets (e.g., amyloid {beta} peptide, {beta} catenin, cardiolipin, claudin, enteric nerve, fibulin, insulin receptor a, and platelet glycoprotein). Principal component analysis with spectrum decomposition based on these autoantibodies indicated an age-dependent stratification of severe COVID-19 patients. Random forest analysis ranked autoantibodies targeting cardiolipin, claudin, and platelet glycoprotein as the three most crucial autoantibodies for the stratification of severe elderly COVID-19 patients. Follow-up analysis using binomial regression found that anti-cardiolipin and anti-platelet glycoprotein autoantibodies indicated a significantly increased likelihood of developing a severe COVID-19 phenotype, presenting a synergistic effect on worsening COVID-19 outcomes. These findings provide new key insights to explain why elderly patients less favorable outcomes have than young individuals, suggesting new associations of distinct autoantibody levels with disease severity.

8.
Vet Surg ; 51(8): 1287-1294, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36056530

ABSTRACT

OBJECTIVE: To report a case of bilateral radial head osteochondritis dissecans (OCD) in a dog treated via lateral elbow arthroscopy portals. STUDY DESIGN: Case report. ANIMALS: Six month old female spayed English bulldog. METHODS: The dog was presented for a left thoracic limb lameness localized to the elbow. Computed tomography revealed bilaterally symmetrical mineralized fragments in the lateral compartment of the elbow joint and blunting of the medial coronoid processes. The fragments were associated with a thin donation bed along the caudolateral articular surface of the radial head with moderate surrounding subchondral bone sclerosis. Bilateral elbow arthroscopy was pursued. Arthroscopy was initiated via a standard medial approach, which allowed for abrasion arthroplasty of the radial incisure and medial coronoid process but provided insufficient access to the radial head lesions. A lateral arthroscopic approach was subsequently performed and provided excellent access to the radial head for fragment retrieval and abrasion arthroplasty. RESULTS: Histopathology of the radial head fragments revealed mild cartilage degeneration and retention of cartilaginous cores within subchondral bone, consistent with OCD. Complete resolution of lameness and elbow pain were observed on clinical examination 5 months postoperatively. CONCLUSION: Radial head OCD can occur as a rare component of elbow dysplasia in growing dogs, and fragment retrieval with abrasion arthroplasty via lateral arthroscopic portals may be an effective treatment option.


Subject(s)
Dog Diseases , Elbow Joint , Joint Diseases , Osteochondritis Dissecans , Animals , Dogs , Female , Arthroscopy/veterinary , Dog Diseases/surgery , Dog Diseases/pathology , Elbow Joint/pathology , Joint Diseases/surgery , Joint Diseases/veterinary , Lameness, Animal , Osteochondritis Dissecans/surgery , Osteochondritis Dissecans/veterinary , Treatment Outcome
9.
PeerJ ; 10: e13507, 2022.
Article in English | MEDLINE | ID: mdl-35846888

ABSTRACT

Background: Public health research frequently requires the integration of information from different data sources. However, errors in the records and the high computational costs involved make linking large administrative databases using record linkage (RL) methodologies a major challenge. Methods: We present Tucuxi-BLAST, a versatile tool for probabilistic RL that utilizes a DNA-encoded approach to encrypt, analyze and link massive administrative databases. Tucuxi-BLAST encodes the identification records into DNA. BLASTn algorithm is then used to align the sequences between databases. We tested and benchmarked on a simulated database containing records for 300 million individuals and also on four large administrative databases containing real data on Brazilian patients. Results: Our method was able to overcome misspellings and typographical errors in administrative databases. In processing the RL of the largest simulated dataset (200k records), the state-of-the-art method took 5 days and 7 h to perform the RL, while Tucuxi-BLAST only took 23 h. When compared with five existing RL tools applied to a gold-standard dataset from real health-related databases, Tucuxi-BLAST had the highest accuracy and speed. By repurposing genomic tools, Tucuxi-BLAST can improve data-driven medical research and provide a fast and accurate way to link individual information across several administrative databases.


Subject(s)
Biomedical Research , Medical Record Linkage , Humans , Medical Record Linkage/methods , Databases, Factual , Brazil , Public Health
10.
Macromol Rapid Commun ; 43(24): e2200249, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35856189

ABSTRACT

Likened to both thermosets and thermoplastics, vitrimers are a unique class of materials that combine remarkable stability, healability, and reprocessability. Herein, this work describes a photopolymerized thiol-ene-based vitrimer that undergoes dynamic covalent exchanges through uncatalyzed transamination of enamines derived from cyclic ß-triketones, whereby the low energy barrier for exchange facilitates reprocessing and enables rapid depolymerization. Accordingly, an alkene-functionalized ß-triketone, 5,5-dimethyl-2-(pent-4-enoyl)cyclohexane-1,3-dione, is devised which is then reacted with 1,6-diaminohexane in a stoichiometrically imbalanced fashion (≈1:0.85 primary amine:triketone). The resulting networks exhibit subambient glass transition temperature (Tg = 5.66 °C) by differential scanning calorimetry. Using a Maxwell stress-relaxation fit, the topology-freezing temperature (Tv ) is calculated to be -32 °C. Small-amplitude oscillatory shear rheological analysis enables to identify a practical critical temperature above which the vitrimer can be successfully reprocessed (Tv,eff ). Via the introduction of excess primary amines, this work can readily degrade the networks into monomeric precursors, which are in turn reacted with diamines to regenerate reprocessable networks. Photopolymerization provides unique spatiotemporal control over the network topology, thereby opening the path for further investigation of vitrimer properties. As such, this work expands the toolbox of chemical upcycling of networks and enables their wider implementation.

11.
Macromol Rapid Commun ; 43(24): e2200487, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35822234

ABSTRACT

Incorporating dynamic covalent bonds into block copolymers provides useful molecular level information during mechanical testing, but it is currently unknown how the incorporation of these units affects the resultant polymer morphology. High-molecular-weight polyisobutylene-b-polystyrene block copolymers containing an anthracene/maleimide dynamic covalent bond are synthesized through a combination of postpolymerization modification, reversible addition-fragmentation chain-transfer polymerization, and Diels-Alder coupling. The bulk morphologies with and without dynamic covalent bond are characterized by atomic force microscopy  and small-angle X-ray scattering, which reveal a strong dependence on annealing time and casting solvent. Morphology is largely unaffected by the inclusion of the mechanophore. The high-molecular-weight polymers synthesized allow interrogation of a large range of polymer domain sizes.

12.
Preprint in English | bioRxiv | ID: ppbiorxiv-480347

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is replacing Delta, the most prevalent variant worldwide from the beginning of 2021 until early 2022. The Omicron variant is highly transmissible and responsible for a new worldwide COVID-19 wave. Herein, we calculated molecular dynamics simulations of the SARS-CoV-2 trimeric spike protein of Wuhan-Hu-1 strain (wild type, WT) and the Omicron variant of concern. Structural analyses reveal that the SpikeOmicron presents more conformational flexibility than SpikeWT, mainly in the N-terminal domain (NTD) and receptor-binding domain (RBD). Such flexibility results in a broader spectrum of different conformations for SpikeOmicron, whereby the RBD can more easily visit an up-conformational state. We reported how the mutations in this variant may influence the intra- and inter-protomer contacts caused by conformational flexibility of the NTD. Based on our analysis, we suggest that the differences in conformational flexibility between SpikeOmicron and SpikeWT may explain the observed gains in infectivity, immune system evasion and transmissibility in this novel variant. Graphical abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

13.
J Wildl Dis ; 58(1): 1-7, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34780647

ABSTRACT

Austwickia (Dermatophilus) chelonae is a filamentous, Gram-positive Actinobacteria in the Dermatophilaceae family. It has caused fatal granulomatous disease in diverse captive reptile species on three continents, but its presence in wild or free-ranging populations was unknown. An adult female gopher tortoise (Gopherus polyphemus) was presented euhydrated, but cachectic and infested with ticks, with two firm, encapsulated masses over the cranioventral neck and right stifle. The tortoise had moderate nonregenerative anemia and evidence of inflammation; plasma biochemistry data was within normal limits. Fine needle aspirate of the neck lesion revealed abundant necrosis and aggregates of cocci. Computed tomography delineated the masses and revealed an additional mass adjacent to the left zygomatic bone. After surgical excision, histology identified chronic granulomas with intralesional filamentous bacteria. Pan-bacterial 16S rRNA PCR and sequencing of the masses identified A. chelonae. Despite treatment with oxytetracycline and ceftazidime, the tortoise deteriorated and was euthanatized. An esophageal lesion consistent with A. chelonae was seen on postmortem examination, although it was determined that the tortoise ultimately succumbed to fungal pneumonia caused by Metarhizium robertsii, an entomopathogenic biotoxin sprayed as insect control. This case reveals A. chelonae is present in free-ranging chelonians in North America. This organism produces a toxin gene similar to diphtheria toxin, one of the most potent known biotoxins, which has not been previously identified outside the genus Corynebacterium. Novel PCR primers were designed for the toxin and rpoB genes, which were amplified and sequenced from two cases and compared with two available genomes. Selection analysis revealed that the toxin gene is under positive selection, which implies it interacts significantly with the immune system, making it a good candidate for immunodiagnostic test development.


Subject(s)
Diphtheria , Turtles , Animals , Female , Actinobacteria , Corynebacterium , Diphtheria/veterinary , RNA, Ribosomal, 16S/genetics , Turtles/microbiology
14.
Cells ; 10(12)2021 12 14.
Article in English | MEDLINE | ID: mdl-34944037

ABSTRACT

Interleukin-6 (IL-6) is a pro-inflammatory cytokine associated with skeletal muscle wasting in cancer cachexia. The control of gene expression by microRNAs (miRNAs) in muscle wasting involves the regulation of thousands of target transcripts. However, the miRNA-target networks associated with IL6-induced muscle atrophy remain to be characterized. Here, we show that IL-6 promotes the atrophy of C2C12 myotubes and changes the expression of 20 miRNAs (5 up-regulated and 15 down-regulated). Gene Ontology analysis of predicted miRNAs targets revealed post-transcriptional regulation of genes involved in cell differentiation, apoptosis, migration, and catabolic processes. Next, we performed a meta-analysis of miRNA-published data that identified miR-497-5p, a down-regulated miRNAs induced by IL-6, also down-regulated in other muscle-wasting conditions. We used miR-497-5p mimics and inhibitors to explore the function of miR-497-5p in C2C12 myoblasts and myotubes. We found that miR-497-5p can regulate the expression of the cell cycle genes CcnD2 and CcnE1 without affecting the rate of myoblast cellular proliferation. Notably, miR-497-5p mimics induced myotube atrophy and reduced Insr expression. Treatment with miR-497-5p inhibitors did not change the diameter of the myotubes but increased the expression of its target genes Insr and Igf1r. These genes are known to regulate skeletal muscle regeneration and hypertrophy via insulin-like growth factor pathway and were up-regulated in cachectic muscle samples. Our miRNA-regulated network analysis revealed a potential role for miR-497-5p during IL6-induced muscle cell atrophy and suggests that miR-497-5p is likely involved in a compensatory mechanism of muscle atrophy in response to IL-6.


Subject(s)
Interleukin-6/adverse effects , MicroRNAs/metabolism , Muscle Cells/metabolism , Muscular Atrophy/genetics , Animals , Cachexia/etiology , Cell Line , Cell Proliferation/drug effects , Cell Proliferation/genetics , Gene Expression Regulation/drug effects , Insulin/metabolism , Mice , MicroRNAs/genetics , Models, Biological , Muscle Cells/drug effects , Muscle Fibers, Skeletal/drug effects , Muscle Fibers, Skeletal/metabolism , Muscle Fibers, Skeletal/pathology , Muscular Atrophy/pathology , Neoplasms/complications , Receptor, IGF Type 1/genetics , Receptor, IGF Type 1/metabolism , Receptor, Insulin/genetics , Receptor, Insulin/metabolism , Reproducibility of Results , Signal Transduction/drug effects
15.
Medicine (Baltimore) ; 100(31): e25368, 2021 Aug 06.
Article in English | MEDLINE | ID: mdl-34397788

ABSTRACT

ABSTRACT: Blood flow restriction (BFR) training applied prior to a subsequent exercise has been used as a method to induce changes in oxygen uptake pulmonary kinetics (O2P) and exercise performance. However, the effects of a moderate-intensity training associated with BFR on a subsequent high-intensity exercise on O2P and cardiac output (QT) kinetics, exercise tolerance, and efficiency remain unknown.This prospective physiologic study was performed at the Exercise Physiology Lab, University of Brasilia. Ten healthy females (mean ±â€ŠSD values: age = 21.3 ±â€Š2.2 years; height = 1.6 ±â€Š0.07 m, and weight = 55.6 ±â€Š8.8 kg) underwent moderate-intensity training associated with or without BFR for 6 minutes prior to a maximal high-intensity exercise bout. O2P, heart rate, and QT kinetics and gross efficiency were obtained during the high-intensity constant workload exercise test.No differences were observed in O2P, heart rate, and QT kinetics in the subsequent high-intensity exercise following BFR training. However, exercise tolerance and gross efficiency were significantly greater after BFR (220 ±â€Š45 vs 136 ±â€Š30 seconds; P < .05, and 32.8 ±â€Š6.3 vs 27.1 ±â€Š5.4%; P < .05, respectively), which also resulted in lower oxygen cost (1382 ±â€Š227 vs 1695 ±â€Š305 mL min-1).We concluded that moderate-intensity BFR training implemented prior to a high-intensity protocol did not accelerate subsequent O2P and QT kinetics, but it has the potential to improve both exercise tolerance and work efficiency at high workloads.


Subject(s)
Exercise/physiology , Ischemic Preconditioning , Regional Blood Flow/physiology , Cross-Sectional Studies , Exercise Tolerance , Female , Heart Rate , Humans , Oxygen Consumption , Prospective Studies , Stroke Volume , Young Adult
16.
Preprint in English | bioRxiv | ID: ppbiorxiv-448436

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is evolving with mutations in the Spike protein, especially in the receptor-binding domain (RBD). The failure of public health measures to contain the spread of the disease in many countries has given rise to novel viral variants with increased transmissibility. However, key questions about how quickly the variants can spread and whether they can cause a more severe disease remain unclear. Herein, we performed a structural investigation using molecular dynamics simulations and determined dissociation constant (KD) values using surface plasmon resonance (SPR) assays of three fastspreading SARS-CoV-2 variants, Alpha, Beta and Gamma ones, as well as genetic factors in the host cells that may be related to the viral infection. Our results suggest that the SARS-CoV-2 variants facilitate their entry into the host cell by moderately increased binding affinities to the human ACE2 receptor, different torsions in hACE2 mediated by RBD variants, and an increased Spike exposure time to proteolytic enzymes. We also found that other host cell aspects, such as gene and isoform expression of key genes for the infection (ACE2, FURIN and TMPRSS2), may have few contributions to the SARS-CoV-2 variants infectivity. In summary, we concluded that a combination of viral and host cell factors allows SARS-CoV-2 variants to increase their abilities to spread faster than wild-type. O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

17.
JCI Insight ; 6(10)2021 05 24.
Article in English | MEDLINE | ID: mdl-34027897

ABSTRACT

The fact that the COVID-19 fatality rate varies by sex and age is poorly understood. Notably, the outcome of SARS-CoV-2 infections mostly depends on the control of cytokine storm and the increasingly recognized pathological role of uncontrolled neutrophil activation. Here, we used an integrative approach with publicly available RNA-Seq data sets of nasopharyngeal swabs and peripheral blood leukocytes from patients with SARS-CoV-2, according to sex and age. Female and young patients infected by SARS-CoV-2 exhibited a larger number of differentially expressed genes (DEGs) compared with male and elderly patients, indicating a stronger immune modulation. Among them, we found an association between upregulated cytokine/chemokine- and downregulated neutrophil-related DEGs. This was correlated with a closer relationship between female and young subjects, while the relationship between male and elderly patients was closer still. The association between these cytokine/chemokines and neutrophil DEGs is marked by a strongly correlated interferome network. Here, female patients exhibited reduced transcriptional levels of key proinflammatory/neutrophil-related genes, such as CXCL8 receptors (CXCR1 and CXCR2), IL-1ß, S100A9, ITGAM, and DBNL, compared with male patients. These genes are well known to be protective against inflammatory damage. Therefore, our work suggests specific immune-regulatory pathways associated with sex and age of patients infected with SARS-CoV-2 and provides a possible association between inverse modulation of cytokine/chemokine and neutrophil transcriptional signatures.


Subject(s)
COVID-19/genetics , Cytokines/genetics , Gene Regulatory Networks , Adult , Age Factors , Aged , COVID-19/epidemiology , COVID-19/immunology , Cytokines/immunology , Female , Humans , Male , Middle Aged , Neutrophils/immunology , Neutrophils/metabolism , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Sex Factors , Transcriptome
18.
Bioinorg Chem Appl ; 2021: 6638229, 2021.
Article in English | MEDLINE | ID: mdl-33953737

ABSTRACT

The solid adducts of SnCl2.(3amt).H2O, SnCl2.2(3amt).H2O, CdCl2.(3amt), CdCl2.2(3amt), SnCl2.(2mct).0.5H2O, SnCl2.2(2mct), CdCl2.(2mct), CdCl2.2(2mct).H2O, SnCl2.(2mcp).1.5H2O, >2.2(2mcp).4H2O, CdCl2.(2mcp), CdCl2.2(2mcp), SnCl2.(4amt).4H2O, SnCl2.2(4amt).1.5H2O, CdCl2.(4amt).H2O, and CdCl2.2(4amt) (where the 3amt, 4amt, 2mct, and 2mcp represent 3-amino-1,2,4-triazole, 4-amino-1,2,4-triazole, 2-mercaptothiazoline, and 2-mercaptopyridine simple organic chelates, respectively) were prepared using a solid-state route and investigated by CHN elemental analysis and infrared spectroscopy. Additionally, we investigated the thermogravimetric characterization and antimicrobial proprieties. It is verified that for 3amt and 4amt adducts, the coordination occurs through nitrogen atom. For 2mct compounds, the coordination occurs through nitrogen (Sn) or sulfur (Cd). For 2mcp adducts, both coordination sites nitrogen and sulfur are involved. By examination of TG curves, it is confirmed that for each hydrated compounds, the first mass loss step is linked with the release of water molecules followed by the release of ligand molecules and sublimation of the metal chloride. Furthermore, it is verified that, considering only the release of ligand molecules (3amp, 4amp, 2mct, or 2mcp), the cadmium adducts are always more stable than the correspondent tin adducts probably due to the formation of cross-linking bonds in these compounds. Finally, of these 16 adducts, 14 showed antimicrobial activities against different bacterial and fungal strains.

19.
BMC Genomics ; 22(1): 237, 2021 Apr 06.
Article in English | MEDLINE | ID: mdl-33823787

ABSTRACT

BACKGROUND: Colossoma macropomum (tambaqui) and Piaractus mesopotamicus (pacu) are good fish species for aquaculture. The tambacu, individuals originating from the induced hybridization of the female tambaqui with the male pacu, present rapid growth and robustness, characteristics which have made the tambacu a good choice for Brazilian fish farms. Here, we used small RNA sequencing to examine global miRNA expression in the genotypes pacu (PC), tambaqui (TQ), and hybrid tambacu (TC), (Juveniles, n = 5 per genotype), to better understand the relationship between tambacu and its parental species, and also to clarify the mechanisms involved in tambacu muscle growth and maintenance based on miRNAs expression. RESULTS: Regarding differentially expressed (DE) miRNAs between the three genotypes, we observed 8 upregulated and 7 downregulated miRNAs considering TC vs. PC; 14 miRNAs were upregulated and 10 were downregulated considering TC vs. TQ, and 15 miRNAs upregulated and 9 were downregulated considering PC vs. TQ. The majority of the miRNAs showed specific regulation for each genotype pair, and no miRNA were shared between the 3 genotype pairs, in both up- and down-regulated miRNAs. Considering only the miRNAs with validated target genes, we observed the miRNAs miR-144-3p, miR-138-5p, miR-206-3p, and miR-499-5p. GO enrichment analysis showed that the main target genes for these miRNAs were grouped in pathways related to oxygen homeostasis, blood vessel modulation, and oxidative metabolism. CONCLUSIONS: Our global miRNA analysis provided interesting DE miRNAs in the skeletal muscle of pacu, tambaqui, and the hybrid tambacu. In addition, in the hybrid tambacu, we identified some miRNAs controlling important molecular muscle markers that could be relevant for the farming maximization.


Subject(s)
Characiformes , MicroRNAs , Animals , Brazil , Characiformes/genetics , Female , High-Throughput Nucleotide Sequencing , Humans , Male , MicroRNAs/genetics , Muscle, Skeletal
20.
J Indian Soc Pedod Prev Dent ; 38(3): 232-237, 2020.
Article in English | MEDLINE | ID: mdl-33004720

ABSTRACT

BACKGROUND: Dental trauma can determine the occurrence of sequelae in the deciduous tooth and due to the anatomical proximity to the germ of the successor permanent tooth, it frequently causes changes to the developing teeth. AIMS: The objective of this study was to analyze clinically and radiographically traumatized primary teeth and permanent successors in children aged 0-8 years. MATERIALS AND METHODS: Initially, a sample selection of medical records was made, designating the patients who fit the requirements; 247 patients were analyzed, totaling 379 traumatized primary teeth and 162 successive permanent teeth. STATISTICAL ANALYSIS: The results were developed using the Proportion Test and the Chi-square test at the 5% significance level. RESULTS: Injuries to hard tissue prevailed (57%), with emphasis on coronary enamel fracture (49.1%). After clinical and radiographic examinations, 78% of traumatized primary teeth maintained pulpal vitality. At the clinical evaluation, the frequency of the developmental disorders observed in permanent successors was 10.5%, with enamel hypocalcification being the most common sequela. 17.3% of the clinical changes in the successor permanent teeth were caused by trauma to the supporting tissue, with the intrusive dislocation being responsible for the largest number of damages (37.5%). CONCLUSION: Based on the results found, it was concluded that the trauma occurring in the primary dentition were recorded and monitored more precisely and about the evaluated successive permanent teeth, except for the prevalence of sequelae found, the other factors are in agreement with the findings in the literature.


Subject(s)
Dental Enamel Hypoplasia , Tooth Avulsion , Child , Child, Preschool , Dentition, Permanent , Humans , Infant , Infant, Newborn , Longitudinal Studies , Tooth, Deciduous
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