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2.
Front Microbiol ; 15: 1385505, 2024.
Article in English | MEDLINE | ID: mdl-38903779

ABSTRACT

Introduction: The concept of a sterile uterus was challenged by recent studies that have described the microbiome of the virgin and pregnant uterus for species including humans and cattle. We designed two studies that tested whether the microbiome is introduced into the uterus when the virgin heifer is first inseminated and whether the origin of the microbiome is the vagina/cervix. Methods: The uterine microbiome was measured immediately before and after an artificial insemination (AI; Study 1; n = 7 AI and n = 6 control) and 14 d after insemination (Study 2; n = 12 AI and n = 12 control) in AI and non-AI (control) Holstein heifers. A third study (Study 3; n = 5 Holstein heifers) that included additional negative controls was subsequently conducted to support the presence of a unique microbiome within the uterus despite the low microbial biomass and regardless of insemination. Traditional bacteriological culture was performed in addition to 16S rRNA gene sequencing on the same samples to determine whether there were viable organisms in addition to those detected based on DNA sequencing (16S rRNA gene sequence). Results and discussion: Inseminating a heifer did not lead to a large change in the microbiome when assessed by traditional methods of bacterial culture or metataxonomic (16S rRNA gene) sequencing (results of Studies 1 and 2). Very few bacteria were cultured from the body or horn of the uterus regardless of whether an AI was or was not (negative control) performed. The cultured bacterial genera (e.g., Bacillus, Corynebacterium, Cutibacterium, Micrococcus, Staphylococcus, and Streptococcus) were typical of those found in the soil, environment, skin, mucous membranes, and urogenital tract of animals. Metataxonomic sequencing of 16S rRNA gene generated a large number of amplicon sequence variants (ASV), but these larger datasets that were based on DNA sequencing did not consistently demonstrate an effect of AI on the abundance of ASVs across all uterine locations compared with the external surface of the tract (e.g., perimetrium; positive control samples for environment contamination during slaughter and collection). Major genera identified by 16S rRNA gene sequencing overlapped with those identified with bacterial culture and included Cutibacterium, Staphylococcus, and Streptococcus.

3.
An Acad Bras Cienc ; 96(2): e20231212, 2024.
Article in English | MEDLINE | ID: mdl-38922279

ABSTRACT

The tumor microenvironment (TME) harbors several cell types, such as tumor cells, immune cells, and non-immune cells. These cells communicate through several mechanisms, such as cell-cell contact, cytokines, chemokines, and extracellular vesicles (EVs). Tumor-derived vesicles are known to have the ability to modulate the immune response. Monocytes are a subset of circulating innate immune cells and play a crucial role in immune surveillance, being recruited to tissues where they differentiate into macrophages. In the context of tumors, it has been observed that tumor cells can attract monocytes to the TME and induce their differentiation into tumor-associated macrophages with a pro-tumor phenotype. Tumor-derived EVs have emerged as essential structures mediating this process. Through the transfer of specific molecules and signaling factors, tumor-derived EVs can shape the phenotype and function of monocytes, inducing the expression of cytokines and molecules by these cells, thus modulating the TME towards an immunosuppressive environment.


Subject(s)
Extracellular Vesicles , Macrophages , Monocytes , Neoplasms , Tumor Microenvironment , Extracellular Vesicles/immunology , Extracellular Vesicles/physiology , Humans , Monocytes/immunology , Tumor Microenvironment/immunology , Neoplasms/immunology , Neoplasms/pathology , Macrophages/immunology , Cytokines , Cell Differentiation
4.
Front Microbiol ; 15: 1385497, 2024.
Article in English | MEDLINE | ID: mdl-38812678

ABSTRACT

Introduction: The possibility that there is a resident and stable commensal microbiome within the pregnant uterus has been supported and refuted by a series of recent studies. One element of most of the initial studies was that they were based primarily on 16S rRNA gene sequencing from bacteria. To account for this limitation, the current study performed both bacterial culture and 16S rRNA gene sequencing in a side-by-side manner (e.g., same tissues isolated from the same animal). Methods: The uteruses of 10 mid-pregnant (156 ± 5 d of gestation) Holstein heifers and cows were collected following slaughter. The external surface of the reproductive tract (positive control for contamination during tissue collection) as well as tissues within the pregnant uterus (placentome, inter-cotyledonary placenta, inter-caruncular endometrium, amnionic fluid, allantoic fluid, fetal abomasum content, and fetal meconium) were sampled for bacterial culture and 16S rRNA gene sequencing. Results: There were 87 unique bacterial species cultured from the external surface of the pregnant reproductive tract (contamination control) and 12 bacterial species cultured from pregnancy tissues. Six out of 10 cattle (60%) exhibited bacterial growth in at least one location within the pregnant uterus. For the metataxonomic results (16S rRNA gene sequencing), a low targeted microbial biomass was identified. Analyses of the detected amplicon sequence variants (ASV) revealed that there were: (1) genera that were prevalent on both the external surface and within the pregnant uterus; (2) genera that were prevalent on the external surface but either not detected or had very low prevalence within the pregnant uterus; and (3) genera that were either not detected or had low prevalence on the external surface but found with relatively high prevalence within the pregnant uterus. Conclusion: There are a small number of viable bacteria in the pregnant uterus. The 16S rRNA gene sequencing detected a microbial community within the pregnant uterus but with a low biomass. These results are consistent with recent studies of the pregnant bovine uterus and leave open the question of whether there is adequate microbial mass to significantly affect the biology of the normal healthy bovine pregnancy.

5.
J Dent ; 146: 105073, 2024 07.
Article in English | MEDLINE | ID: mdl-38782176

ABSTRACT

OBJECTIVES: Evaluate, in vitro, the effect of incorporating nano-sized sodium trimetaphosphate (TMPnano) and phosphorylated chitosan (Chi-Ph) into resin-modified glass ionomer cement (RMGIC) used for orthodontic bracket cementation, on mechanical, fluoride release, antimicrobial and cytotoxic properties. METHODS: RMGIC was combined with Chi-Ph (0.25%/0.5%) and/or TMPnano (14%). The diametral compressive/tensile strength (DCS/TS), surface hardness (SH) and degree of conversion (%DC) were determined. For fluoride (F) release, samples were immersed in des/remineralizing solutions. Antimicrobial/antibiofilm activity was evaluated by the agar diffusion test and biofilm metabolism (XTT). Cytotoxicity in fibroblasts was assessed with the resazurin method. RESULTS: After 24 h, the RMGIC-14%TMPnano group showed a lower TS value (p < 0.001); after 7 days the RMGIC-14%TMPnano-0.25%Chi-Ph group showed the highest value (p < 0.001). For DCS, the RMGIC group (24 h) showed the highest value (p < 0.001); after 7 days, the highest value was observed for the RMGIC-14%TMPnano-0.25%Chi-Ph (p < 0.001). RMGIC-14%TMPnano, RMGIC-14%TMPnano-0.25%Chi-Ph, RMGIC-14%TMPnano-0.5%Chi-Ph showed higher and similar release of F (p > 0.001). In the SH, the RMGIC-0.25%Chi-Ph; RMGIC-0.5%Chi-Ph; RMGIC-14%TMPnano-0.5%Chi-Ph groups showed similar results after 7 days (p > 0.001). The RMGIC-14%TMPnano-0.25%Chi-Ph group showed a better effect on microbial/antibiofilm growth, and the highest efficacy on cell viability (p < 0.001). After 72 h, only the RMGIC-14%TMPnano-0.25%Chi-Ph group showed cell viability (p < 0.001). CONCLUSION: The RMGIC-14%TMPnano-0.25%Chi-Ph did not alter the physical-mechanical properties, was not toxic to fibroblasts and reduced the viability and metabolism of S. mutans. CLINICAL RELEVANCE: The addition of phosphorylated chitosan and organic phosphate to RMGIC could provide an antibiofilm and remineralizing effect on the tooth enamel of orthodontic patients, who are prone to a high cariogenic challenge due to fluctuations in oral pH and progression of carious lesions.


Subject(s)
Anti-Bacterial Agents , Biofilms , Chitosan , Fibroblasts , Fluorides , Glass Ionomer Cements , Materials Testing , Chitosan/pharmacology , Anti-Bacterial Agents/pharmacology , Glass Ionomer Cements/pharmacology , Glass Ionomer Cements/chemistry , Biofilms/drug effects , Fibroblasts/drug effects , Phosphorylation , Fluorides/pharmacology , Hardness , Tensile Strength , Surface Properties , Compressive Strength , Nanoparticles , Resin Cements/chemistry , Polyphosphates/pharmacology , Dental Cements/pharmacology , Dental Cements/chemistry , Cell Survival/drug effects , Streptococcus mutans/drug effects , Animals , Phosphates/pharmacology , Humans , Orthodontic Brackets
6.
Biol Reprod ; 2024 May 05.
Article in English | MEDLINE | ID: mdl-38704744

ABSTRACT

Cows with metritis (uterine disease) during the first 1 to 2 wk postpartum have lower pregnancy rates when inseminated later postpartum (typically >10 wk). We hypothesized that metritis and the disease-associated uterine microbiome have a long-term effect on endometrial gene expression. Changes in gene expression may inform a mechanism through which disease lowers pregnancy rates. A total of 20 cows were enrolled at 1 to 2 wk postpartum to either metritis (clinical disease; n = 10) or healthy (control; n = 10) groups and randomly assigned to be slaughtered at approximately 80 d and 165 d postpartum (mid-lactation). The microbiome of the reproductive tract was sampled to confirm the presence of pathogens that are typical of metritis. In addition to the original clinical diagnosis, study cows were retrospectively assigned to uterine-disease and control groups based on the composition of their microbiome. There was no effect of early postpartum uterine disease on the uterine microbiome at mid-lactation (time of slaughter). Nonetheless, early postpartum metritis and the disease microbiome were associated with a large number of differentially-expressed genes at mid-lactation primarily in the caruncular compared with the inter-caruncular endometrium. Gene enrichment analysis identified oxidative phosphorylation as the primary pathway increased in caruncular endometrium of diseased cows whereas growth factor signaling pathways were reduced. The current study demonstrated that metritis and a uterine disease microbiome leave a sustained imprint on gene expression in the caruncular endometrium that may explain lower fertility in cows with postpartum uterine disease.

7.
Anim Reprod Sci ; 265: 107475, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38663149

ABSTRACT

A greater understanding of factors influencing fertility is essential to improve pregnancy rates and reduce the occurrence of embryonic mortality in beef herds. The objective of the current study was to evaluate retrospective data of pregnancy per artificial insemination (P/AI) and pregnancy loss in Nelore females subjected to timed-AI (TAI) in Brazil. Data from 40,104 TAI collected from six breeding seasons (2016-2022) were analyzed, and the effects of animal category (e.g., classification based on age and parity), farm, month of parturition, sire, sire breed (Nelore vs Angus), estrus expression at TAI, animal temperament, and body condition scores (BCS) were evaluated. P/AI and pregnancy loss were affected (P < 0.001) by animal category. There was also an effect of farm (P = 0.0013) on P/AI and pregnancy loss (P = 0.001), as P/AI ranged from 49.28% and 55.58% and pregnancy loss from 3.37% to 6.89% across the herds evaluated. Month of parturition also affected (P < 0.001) P/AI and was higher for cows that became pregnant at the beginning of the previous breeding season. Calmer animals, presenting lower velocity scores while exiting the chute following TAI, achieved higher P/AI (P < 0.001). Lower BCS at TAI was associated (P < 0.001) with increased pregnancy loss, and BCS gain following AI was associated (P < 0.001) with reduced rates of embryonic mortality. There was a major effect (P < 0.001) of sire on P/AI and pregnancy loss, as P/AI ranged from 11% to 79%, and embryonic mortality from 0% to 40% for the bulls used in the study, highlighting the importance of the sire fertility on overall pregnancy success. Results from the current study reinforce the idea that animal age and parity at the beginning of the breeding season, BCS at the onset of estrous synchronization, BCS gain following AI, estrus expression at TAI, sire, and month of parturition are important factors influencing P/AI and rates of embryonic mortality in beef herds.


Subject(s)
Insemination, Artificial , Animals , Female , Pregnancy , Cattle/physiology , Insemination, Artificial/veterinary , Brazil , Retrospective Studies , Pregnancy Rate , Estrus Synchronization , Abortion, Veterinary
8.
Res Sq ; 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38659779

ABSTRACT

Background: Postpartum uterine disease (metritis) is common in dairy cows. The disease develops within 1 week after calving and is associated with microbial dysbiosis, fever, and fetid uterine discharge. Cows with metritis have a greater likelihood of developing endometritis and infertility later postpartum. Antibiotic treatment is used to relieve symptoms of metritis but the capacity of antibiotic treatment to improve fertility later postpartum is inconsistent across published studies. We hypothesized that an antibiotic has only a short-term effect on the uterine microbiome and does not change the progression of disease from metritis to endometritis. To test this hypothesis, we studied the effects of systemic antibiotic given to cows diagnosed with metritis and healthy cows early postpartum on the development of endometritis and the uterine microbiome at 1 month postpartum. Results: Cows diagnosed with metritis were compared to healthy ones in a 2 × 2 factorial design, where they were either treated with an antibiotic (ceftiofur hydrochloride) at 7 to 10 days postpartum or left untreated. Cows were slaughtered at one month postpartum and the uterus was assessed for endometritis (presence of purulent material in the uterine lumen and inflammation in the endometrium) and uterine samples were collected for bacteriology and metagenomics (16S rRNA gene sequencing). As expected, the uterine microbiome at disease diagnosis had dysbiosis of typical metritis pathogens (e.g., Fusobacterium, Bacteroides, and Porphyromonas) in diseased compared with healthy cows. At one month postpartum, there was a tendency for more endometritis in metritis cows compared with healthy but antibiotic treatment had no effect on endometritis prevalence regardless of the original disease diagnosis. Likewise, when bacteria were cultured or sequenced, there were a greater number of species (culture) or amplicon sequence variants (ASV; sequencing) in the uterine lumen of cows with metritis. However, antibiotic treatment had no effect on the prevalence of cultured species or the composition of the detected ASV. The uterine microbiome at 1 month postpartum was associated with the clinical observation of the uterus (endometritis or healthy). Conclusions: Early postpartum antibiotic treatment only provides temporary resolution of uterine dysbiosis that is not sustained long-term. Failure to resolve the dysbiosis is associated with a greater prevalence of endometritis in cows with metritis, and the occurrence of endometritis significantly impacts fertility later postpartum.

9.
J Maxillofac Oral Surg ; 23(1): 75-80, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38312968

ABSTRACT

Background: The early detection of impacted teeth is essential for the prevention of future malocclusions and possible lesions. The aim of this study is to assess the prevalence of impacted teeth and associated pathological lesions. Methods: One thousand six hundred and two panoramic radiographs were analyzed for this retrospective study. The prevalence of impacted teeth, the presence of supernumerary teeth and cystic or tumoral lesions associated, and the type of angulation of third molars using Winter's classification were accessed. The descriptive statistics and the Chi-squared test were performed (P < 0.05). Results: One thousand three hundred and ninety-seven panoramic radiographs fulfilled impacted criteria. A prevalence of 541 (38.7%) impacted teeth was observed, with the female gender significantly higher (P < 000.1). Of the total impacted teeth (n = 541), the overall mean impacted of lower third molars was 55.6%. Twenty-nine (5.3%) supernumerary teeth and four lesions were verified. The angulations most observed in the upper (76.6%) and lower (39.2%) third molars were vertical (P < 000.1) and mesioangulated (P < 000.1), respectively. Conclusion: The impacted tooth prevalence was 38.7%, more common in females than in males. The lower third molars presented the highest prevalence of impacted, and the most common angulations were vertical and mesioangulated. Only four associated lesions were observed.

10.
Purinergic Signal ; 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-37975950

ABSTRACT

Trypanosoma cruzi is the pathogen of Chagas disease, a neglected tropical disease that affects more than 6 million people worldwide. There are no vaccines to prevent infection, and the therapeutic arsenal is very minimal and toxic. The unique E-NTPDase of T. cruzi (TcNTPDase1) plays essential roles in adhesion and infection and is a virulence factor. Quercetin is a flavonoid with antimicrobial, antiviral, and antitumor activities. Its potential as a partial inhibitor of NTPDases has also been demonstrated. In this work, we synthesized the non-natural L-glycoside derivatives of quercetin and evaluated them as inhibitors of recombinant TcNTPDase1 (rTcNTPDase1). These compounds, and quercetin and miquelianin, a natural quercetin derivative, were also tested. Compound 16 showed the most significant inhibitory effect (94%). Quercetin, miquelianin, and compound 14 showed inhibition close to 50%. We thoroughly investigated the inhibitory effect of 16. Our data suggested a competitive inhibition with a Ki of 8.39 µM (± 0.90). To better understand the interaction of compound 16 and rTcNTPDase1, we performed molecular dynamics simulations of the enzyme and docking analyses with the compounds. Our predictions show that compound 16 binds to the enzyme's catalytic site and interacts with important residues for NTPDase activity. As an inhibitor of a critical T. cruzi enzyme, (16) could be helpful as a starting point in the developing of a future treatment for Chagas disease. Furthermore, the discovery of (16) as an inhibitor of TcNTPDase1 may open new avenues in the study and development of new inhibitors of E-NTPDases.

11.
Purinergic Signal ; 2023 Nov 24.
Article in English | MEDLINE | ID: mdl-37999896

ABSTRACT

Leishmania braziliensis is a pathogenic protozoan parasite that causes American Tegumentary Leishmaniasis (ATL), an important tropical neglected disease. ENTPDases are nucleotidases that hydrolyze intracellular and/or extracellular nucleotides. ENTPDases are known as regulators of purinergic signalling induced by extracellular nucleotides. Leishmania species have two isoforms of ENTPDase, and, particularly, ENTPDase2 seems to be involved in infectivity and virulence. In this study, we conducted the heterologous expression and biochemical characterization of the recombinant ENTPDase2 of L. braziliensis (rLbNTPDase2). Our results show that this enzyme is a canonical ENTPDase with apyrase activity, capable of hydrolysing triphosphate and diphosphate nucleotides, and it is dependent on divalent cations (calcium or magnesium). Substrate specificity was characterized as UDP>GDP>ADP>GTP>ATP=UTP. The enzyme showed optimal activity at a neutral to basic pH and was partially inhibited by suramin and DIDS. Furthermore, the low apparent Km for ADP suggests that the enzyme may play a role in adenosine-mediated signalling. The biochemical characterization of this enzyme can open new avenues for using LbNTPDase2 as a drug target.

12.
Sensors (Basel) ; 23(13)2023 Jun 26.
Article in English | MEDLINE | ID: mdl-37447772

ABSTRACT

Traffic Sign Recognition (TSR) is one of the many utilities made possible by embedded systems with internet connections. Through the usage of vehicular cameras, it's possible to capture and classify traffic signs in real time with Artificial Intelligence (AI), more specifically, Convolutional Neural Networks (CNNs) based techniques. This article discusses the implementation of such TSR systems, and the building process of datasets for AI training. Such datasets include a brand new class to be used in TSR, vegetation occlusion. The results show that this approach is useful in making traffic sign maintenance faster since this application turns vehicles into moving sensors in that context. Leaning on the proposed technique, identified irregularities in traffic signs can be reported to a responsible body so they will eventually be fixed, contributing to a safer traffic environment. This paper also discusses the usage and performance of different YOLO models according to our case studies.


Subject(s)
Artificial Intelligence , Deep Learning , Brazil , Internet , Neural Networks, Computer
13.
Fitoterapia ; 169: 105623, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37500018

ABSTRACT

Alpinia zerumbet is a plant from the Zingiberaceae family, popularly used for hypertension treatment. Several studies have demonstrated Alpinia zerumbet vasodilator effect on conductance vessels but not on resistance vessels. Thereby, the aim of this study was to verify the vasodilator effect of the essential oil of Alpinia zerumbet (EOAz) on isolated rat resistance arteries and characterize its mechanism of action. Therefore, the effect of EOAz (3 to 3000 µg/mL) was verified in second-order branches of the mesenteric artery (SOBMA) pre-contracted by KCl and U46619. To study the mechanism of action, the influence of several inhibitors (TEA, 4-AP, Glibenclamide, Atropine, L-NAME, ODQ and indomethacin) on the vasodilator effect of EOAz was evaluated. Some protocols were also performed aiming to study the effect of EOAz on Ca2+ influx and release from intracellular storage. Furthermore, the binding energy of the main constituents with calcium channels were evaluated by molecular docking. Results showed an endothelium-independent vasorelaxant effect of EOAz on SOBMA, and only ODQ and L-NAME produced significant alteration on its pEC50. Regarding the calcium assays, contraction reduction caused by incubation with EOAz was observed in all three protocols. Hence, our results suggest that EOAz has a vasodilator effect mediated by inhibition of Ca2+ influx and release from intracellular storage, as well as an activation of the NOS/sGC pathway.


Subject(s)
Alpinia , Oils, Volatile , Rats , Animals , Vasodilator Agents/pharmacology , Oils, Volatile/pharmacology , Alpinia/chemistry , Calcium , NG-Nitroarginine Methyl Ester/pharmacology , Molecular Docking Simulation , Molecular Structure , Arteries , Vasodilation , Endothelium, Vascular
14.
Pharmaceuticals (Basel) ; 16(2)2023 Jan 30.
Article in English | MEDLINE | ID: mdl-37259357

ABSTRACT

Targeted antitumour therapy has revolutionized the treatment of several types of tumours. Among the validated targets, phosphatidylinositol-3 kinase (PI3K) deserves to be highlighted. Several PI3K inhibitors have been developed for the treatment of cancer, including gedatolisib (4). This inhibitor was elected as a prototype and molecular modifications were planned to design a new series of simplified gedatolisib analogues (5a-f). The analogues were synthesised, and the comparative cytotoxic activity profile was studied in phenotypic models employing solid and nonadherent tumour cell lines. Compound 5f (LASSBio-2252) stood out as the most promising of the series, showing good aqueous solubility (42.38 µM (pH = 7.4); 39.33 µM (pH = 5.8)), good partition coefficient (cLogP = 2.96), cytotoxic activity on human leukemia cell lines (CCRF-CEM, K562 and MOLT-4) and an excellent metabolic stability profile in rat liver microsomes (t1/2 = 462 min; Clapp = 0.058 mL/min/g). The ability of 5f to exert its cytotoxic effect through modulation of the PI3K pathway was demonstrated by flow cytometry analysis in a comparative manner to gedatolisib.

15.
Saúde Redes ; 9(2): 21, jun. 2023.
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1444171

ABSTRACT

No Brasil, as medidas de isolamento social para o enfrentamento à propagação do COVID-19 demandaram a paralisação das atividades presenciais das escolas médicas. Com a pequena quantidade de estudos que tratam das práticas pedagógicas utilizadas nesse período, este artigo busca analisar por meio de uma revisão da literatura as experiências de Instituições de Ensino Superior brasileiras durante a pandemia de COVID-19, entendendo seu impacto na formação de novos médicos. Os dados foram coletados nos bancos de dados PUBMED e Biblioteca Virtual em Saúde, com a inclusão de 20 trabalhos publicados de abril de 2020 a dezembro de 2022. A partir do conteúdo dos textos selecionados, criouse quatro categorias a serem consideradas. Após análise, conclui-se que o ensino remoto trouxe diversas consequências negativas para o processo de ensino-aprendizagem na formação médica. Foram evidenciados aspectos como a ampliação das dificuldades de acesso à educação encontrada por estudantes de baixa renda, além do deterioramento da saúde mental de docentes e discentes. Quanto às novas estratégias pedagógicas, percebeu-se uso de ferramentas digitais e metodologias ativas com caráter emergencial e temporário, consideradas satisfatórias, em sua maioria, mas repletas de insuficiências quanto à qualidade de ensino.

16.
Front Immunol ; 14: 886601, 2023.
Article in English | MEDLINE | ID: mdl-36960058

ABSTRACT

Introduction: Pulmonary fibrosis is a destructive, progressive disease that dramatically reduces life quality of patients, ultimately leading to death. Therapeutic regimens for pulmonary fibrosis have shown limited benefits, hence justifying the efforts to evaluate the outcome of alternative treatments. Methods: Using a mouse model of bleomycin (BLM)-induced lung fibrosis, in the current work we asked whether treatment with pro-resolution molecules, such as pro-resolving lipid mediators (SPMs) could ameliorate pulmonary fibrosis. To this end, we injected aspirin-triggered resolvin D1 (7S,8R,17R-trihydroxy-4Z,9E,11E,13Z,15E19Z-docosahexaenoic acid; ATRvD1; i.v.) 7 and 10 days after BLM (intratracheal) challenge and samples were two weeks later. Results and discussion: Assessment of outcome in the lung tissues revealed that ATRvD1 partially restored lung architecture, reduced leukocyte infiltration, and inhibited formation of interstitial edema. In addition, lung tissues from BLM-induced mice treated with ATRvD1 displayed reduced levels of TNF-α, MCP-1, IL-1-ß, and TGF-ß. Of further interest, ATRvD1 decreased lung tissue expression of MMP-9, without affecting TIMP-1. Highlighting the beneficial effects of ATRvD1, we found reduced deposition of collagen and fibronectin in the lung tissues. Congruent with the anti-fibrotic effects that ATRvD1 exerted in lung tissues, α-SMA expression was decreased, suggesting that myofibroblast differentiation was inhibited by ATRvD1. Turning to culture systems, we next showed that ATRvD1 impaired TGF-ß-induced fibroblast differentiation into myofibroblast. After showing that ATRvD1 hampered extracellular vesicles (EVs) release in the supernatants from TGF-ß-stimulated cultures of mouse macrophages, we verified that ATRvD1 also inhibited the release of EVs in the bronco-alveolar lavage (BAL) fluid of BLM-induced mice. Motivated by studies showing that BLM-induced lung fibrosis is linked to angiogenesis, we asked whether ATRvD1 could blunt BLM-induced angiogenesis in the hamster cheek pouch model (HCP). Indeed, our intravital microscopy studies confirmed that ATRvD1 abrogates BLM-induced angiogenesis. Collectively, our findings suggest that treatment of pulmonary fibrosis patients with ATRvD1 deserves to be explored as a therapeutic option in the clinical setting.


Subject(s)
Pulmonary Fibrosis , Humans , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/metabolism , Aspirin/pharmacology , Docosahexaenoic Acids/pharmacology , Docosahexaenoic Acids/therapeutic use , Lung/pathology , Bleomycin/pharmacology , Transforming Growth Factor beta/metabolism
17.
Polymers (Basel) ; 15(1)2023 Jan 03.
Article in English | MEDLINE | ID: mdl-36616585

ABSTRACT

Recent formulations of resin-based composites have incorporated different combinations of materials. However, the mechanical and bonding behavior of these materials with intraradicular posts are unclear. This study aimed to evaluate the effect of light-cure and dual-cure resin composite posts on the fracture resistance of endodontically-treated teeth. Materials and Methods: Ninety extracted human upper canines were selected and randomly divided into nine groups (n=10): (G1) endodontically treated teeth without endodontic posts; (G2) glass-fiber post cemented with glass-ionomer cement; (G3) endodontic post by dual-cure composite resin (Rebilda DC); (G4) endodontic post by dual-cure composite resin (Cosmecore); (G5) endodontic post by dual-cure composite resin (Bis-Core); (G6) endodontic post by light-cure composite resin; (G7) glass-fiber post customized with flowable composite resin; (G8) glass-fiber post cemented with light-cure composite resin; (G9) glass-fiber post cemented with self-adhesive resin cement. After the post insertion, all specimens were subjected to mechanical (250,000 cycles) and thermocycling (6000 cycles, 5 °C/55 °C) and immediate loading at 45 degrees in a universal testing machine until fracture. The data were analyzed by one-way ANOVA and multiple comparisons using the Fisher LSD Method (p < 0 05). Results: The mean failure loads (±SD) for the groups ranged from 100.7 ± 22.6 N to 221.9 ± 48.9 N. The G1 group (without endodontic posts) had a higher fracture strength than all experimental groups (p < 0.001). Conclusions: Within the limitations, the light- and dual-cure post technique did not present lower fracture resistance values as compared to the conventional glass-fiber post.

18.
Toxicon ; 223: 107011, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36584790

ABSTRACT

Envenomation by Bothrops snakes and Apis mellifera bee may imply systemic disorders which affect well-perfused organs such as kidneys, a process that can lead to acute renal failure. Nevertheless, there is scarce information regarding a direct renal cell effect and the putative antagonism by antivenoms. Here the cytotoxic effect of B. jararacussu and A. mellifera venoms was evaluated in the renal proximal tubule cell line LLC-PK1, as well as the antagonism of this effect by heparin. B. jararacussu venom showed significant cytotoxicity as assessed by LDH release and MTT reduction, with a sharp decline of the cell number after 180 min (>90% at 50 µg/mL). A. mellifera venom produced a much faster and potent cytotoxic activity, conferring almost no viable cells after 15 min at 25 µg/mL. Phase contrast microscopy revealed that while B. jararacussu venom induced a progressive loss of cell adhesion and detachment, A. mellifera venom promoted a rapid plasma membrane disruption and nuclear condensation suggestive of necrotic cell death. Pre-incubation of both venoms with heparin for 30 min significantly reduced cytotoxicity. Our results demonstrate direct toxicity of B. jararacussu and A. mellifera venoms toward renal cells but with distinct kinetics and cell pattern, suggesting different mechanisms of action. In addition, the antagonistic, cytoprotective effect of heparin ascribes such compound as a promising drug for preventing renal failure from envenomation.


Subject(s)
Antineoplastic Agents , Bothrops , Crotalid Venoms , Bees , Animals , Heparin/pharmacology , Antivenins/pharmacology , Crotalid Venoms/toxicity , Kidney
19.
J Prosthet Dent ; 2022 Nov 10.
Article in English | MEDLINE | ID: mdl-36372587

ABSTRACT

STATEMENT OF PROBLEM: Computer-guided implant surgery facilitated by intraoral scanning may enhance the efficiency of the digital workflow. However, it is necessary to assess technique accuracy to evaluate the accuracy of implant placement. PURPOSE: The purpose of this clinical study was to evaluate the accuracy of a virtual computer-aided design and computer-aided manufacturing (CAD-CAM) static guided surgery technique associated with intraoral scanning in partially edentulous participants by analyzing the overlap among preoperative and postoperative cone beam computed tomography (CBCT) scans, virtual planning, and the guided surgery performed. MATERIAL AND METHODS: Eleven partially edentulous participants underwent CBCT and intraoral scanning (TRIOS3). Data were integrated into a software program (ImplantViewer 3.5) for the virtual planning of implants and 3-dimensional (3D) printing of the prototype CAD-CAM surgical guide. A total of 18 implants were placed using the CAD-CAM static computer-aided implant surgery technique (Strong SW). After 15 days, postoperative CBCT scans were made and 4 variables (angular, coronal, apical, and vertical deviation) were measured to compare the virtually planned implants and the implants placed by analyzing the overlap between preoperative and postoperative of the virtual planning and guided surgery performed using the ImplantViewer 3.5 and Rhino 6 software programs. RESULTS: Deviations were found in all parameters analyzed. The mean angular deviation was 2.68 ±1.62 degrees; mean coronal deviation, 0.82 ±0.44 mm; mean apical deviation, 1.14 ±0.44 mm; and mean vertical deviation, 0.62 ±0.44 mm. CONCLUSIONS: The implants placed using the CAD-CAM static guided surgery technique associated with intraoral scanning in partially edentulous participants exhibited angular and linear deviations when compared with virtual planning implants. However, these deviations were not clinically significant.

20.
Polymers (Basel) ; 14(19)2022 Sep 26.
Article in English | MEDLINE | ID: mdl-36235967

ABSTRACT

Resin-based composites (RBCs) have transformed restorative dentistry and its procedures. However, the characteristics of RBCs have been modified over the years to enhance the physical and chemical properties of the materials. This context raises the need for studies that evaluate whether the properties of the RBCs that are commercially available are clinically adequate with different curing modes. This study aimed to evaluate the mechanical behavior of commercial RBCs after undergoing different curing modes. Twenty-three RBCs of different classes were evaluated. For curing the specimens, a microwave (BMS45, Brastemp) (for 3 min at 450 W) and three LED units were used: an Emitter A Fit (Schuster (second generation)) (light-curing for 15 s with an irradiance of 1250 mW/cm2), VALO (Ultradent (third generation)) (light-curing for 15 s with an irradiance of 1100 mW/cm2), and Emitter Now Duo (Schuster (second generation)) (light-curing for 15 s with an irradiance of 1100 mW/cm2). A total of 670 RBC specimens of 8 mm in diameter and 1 mm in depth were obtained. Afterward, a biaxial flexure strength test was performed until the failure of the specimens, using a universal testing machine set at a speed of 0.5 mm/min. The same specimens were subjected to infrared spectroscopy for evaluating the degree of conversion. Tukey's test was used for multiple comparisons at a significance level of 5%. The light-curing mode did not affect the flexure strength of the RBCs (p > 0.05), but the type and shade of RBCs did so (p < 0.05). In conclusion, the type of RBC directly interferes with the mechanical behavior of the material. However, the curing modes within the same RBC did not change the mechanical properties.

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