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1.
J Biol Inorg Chem ; 29(1): 159-168, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38182820

RESUMEN

Melanoma is the most aggressive and lethal type of skin cancer due to its characteristics such as high metastatic potential and low response rate to existing treatment modalities. In this way, new drug prototypes are being studied to solve the problem of treating patients with melanoma. Among these, ruthenium-based metallopharmaceuticals may be promising alternatives due to their antitumor characteristics and low systemic toxicity. In this context, the present study evaluated the antineoplastic effect of the ruthenium complex [Ru(mtz)(dppe)2]PF6-2-mercaptothiazoline-di-1,2-bis(diphenylphosphine) ethaneruthenium(II), namely RuMTZ, on human melanoma (A-375) and murine (B16-F10) cells, considering different approaches. Through XTT colorimetric and clonogenic efficiency assays, the complex revealed the selective cytotoxic activity, with the lowest IC50 (0.4 µM) observed for A375 cells. RuMTZ also induced changes in cell morphology, increased cell population in the sub-G0 phase and inhibiting cell migration. The levels of γH2AX and cleaved caspase 3 proteins were increased in both cell lines treated with RuMTZ. These findings indicated that the cytotoxic activity of RuMTZ on melanoma cells is related, at least in part, to the induction of DNA damage and apoptosis. Therefore, RuMTZ exhibited promising antineoplastic activity against melanoma cells.


Asunto(s)
Antineoplásicos , Complejos de Coordinación , Melanoma , Rutenio , Tiazolidinas , Humanos , Animales , Ratones , Rutenio/farmacología , Complejos de Coordinación/farmacología , Melanoma/tratamiento farmacológico , Ligandos , Antineoplásicos/farmacología , Apoptosis , Daño del ADN , Línea Celular Tumoral
2.
Clin Oral Investig ; 28(1): 119, 2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38277034

RESUMEN

OBJECTIVES: To evaluate the anti-demineralizing effect of a mouthwash comprising pomegranate peel extract (PPE 3%), sodium trimetaphosphate (TMP 0.3%), and fluoride (F 225 ppm) in an in situ study, and to assess its irritation potential in an ex vivo study. METHODS: This double-blind crossover study was conducted in four phases with 7 days each. Twelve volunteers used palatal appliances containing enamel blocks, which were subjected to cariogenic challenges. The ETF formulation (PPE + TMP + F, pH 7.0), TF formulation (TMP + F, pH 7.0), deionized water (W, pH 7.0), and essential oil commercial mouthwash (CM, 220 ppm F, pH 4.3) were dropped onto the enamel twice daily. The percentage of surface hardness loss, integrated loss of subsurface hardness, calcium, phosphorus, and fluoride in enamel and biofilms were determined. In addition, alkali-soluble extracellular polysaccharide concentrations were analyzed in the biofilms. The irritation potential was evaluated using the hen's egg chorioallantoic membrane test through the vascular effect produced during 300-s of exposure. RESULTS: ETF was the most efficacious in preventing demineralization. It also showed the highest concentrations of calcium and phosphorus in the enamel and in the biofilm, as well as the lowest amount of extracellular polysaccharides in the biofilm. In the eggs, ETF produced light reddening, whereas CM led to hyperemia and hemorrhage. CONCLUSIONS: The addition of PPE to formulations containing TMP and F increased its anti-demineralizing property, and this formulation presented a lower irritation potential than the CM. CLINICAL RELEVANCE: ETF can be a promising alternative alcohol-free mouthwash in patients at high risk of caries.


Asunto(s)
Antisépticos Bucales , Extractos Vegetales , Granada (Fruta) , Desmineralización Dental , Humanos , Calcio/análisis , Estudios Cruzados , Esmalte Dental , Fluoruros , Dureza , Antisépticos Bucales/química , Antisépticos Bucales/farmacología , Fósforo , Polifosfatos , Desmineralización Dental/prevención & control , Extractos Vegetales/farmacología
3.
J Technol Transf ; 48(1): 361-391, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35291661

RESUMEN

University-industry collaboration (UIC) projects are complex undertakings, that can involve multiple parties or stakeholders. Effective management of UICs can mean the difference between success and failure, in terms of technology transfer and research commercialization. This research paper focuses on the micro-level analysis of UICs and in particular the project management practices that can help major UICs deliver benefits and broader societal impact. PM has been evolving toward more hybrid approaches involving both traditional and agile practices. A conceptualization of a hybrid approach is presented based on a literature review. This conceptualization is then used as a starting point for exploratory empirical research. Participant observation, document analysis, and thirty semi-structured interviews were conducted in a large UIC case study to help identify PM practices and check their relevance. Data analysis led to a framework comprising 29 transversal or must-have practices distributed throughout the project lifecycle and 30 contingent or optional practices, divided into traditional, agile and common. This research extends the existing knowledge on UICs by giving a micro-level perspective on managing UIC projects and providing evidence of the adoption of hybrid approaches to assure the overall governance of significant inter-organizational endeavors. The framework provides a roadmap for future major UIC projects.

4.
Reprod Domest Anim ; 58(1): 117-128, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36156318

RESUMEN

In the present study, we investigated the spent culture media of in vitro produced (IVP) bovine embryos which did (group Pregnant) or did not (group Non-pregnant) establish pregnancy after transfer. For that purpose, IVP embryos on D5 were transferred to individual droplets for the last 48 h of culture. Embryos at the blastocyst stage were then transferred to synchronized recipients, while respective culture media drops were collected and evaluated individually. The list of metabolites present in spent culture media was obtained by electrospray ionization mass spectrometry (ESI-MS) and analysed with Metaboanalyst® to characterize the metabolic profile of each group. The spectrometric analysis showed that pathways related to lipid metabolism, particularly fatty acids degradation via beta-oxidation, were more present in the Pregnant group whereas no significant pathway was identified in the group Non-pregnant. By using this method, we were able to identify a metabolic signature in culture media that allows for a better comprehension of preferential metabolic routes taken by the most viable embryos. These findings offer great insights into the biochemistry of embryo development and reveal a potential target for the development of better-quality IVP systems, as well as tools to identify bovine embryos with greater chances to establish and maintain pregnancy.


Asunto(s)
Metabolismo de los Lípidos , Resultado del Embarazo , Embarazo , Femenino , Animales , Bovinos , Medios de Cultivo/química , Blastocisto/metabolismo , Desarrollo Embrionario , Técnicas de Cultivo de Embriones/veterinaria , Fertilización In Vitro/veterinaria
5.
Am J Dent ; 36(3): 143-150, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37364192

RESUMEN

PURPOSE: To evaluate the influence of different surface treatments on the clinical behavior of non-carious cervical sclerotic lesions (NCCLs) over an 18-month follow-up period. METHODS: 128 NCCLs from 32 volunteers were randomized into four groups (n=32): G1-control, without preoperative treatment of the dentin surface; G2, dentin conditioning with 17% ethylenediaminetetracetic acid (EDTA) for 2 minutes; G3, increase in dentin surface roughness with diamond bur and G4, increase in dentin surface roughness with diamond bur + dentin conditioning with 17% EDTA for 2 minutes. RESULTS: Differences between groups were tested using the Friedman test (α= 0.05). A questionnaire was administered to volunteers about risk factors related to NCCLs. The relationship between the questionnaire data and the clinical performance of the restorations was analyzed using the multiple logistic regression test (α= 0.05). The variables related to parafunctional habits, anxiety and/or depression were significantly related to the manifestation of postoperative sensitivity. Roughening the sclerotic dentin with a diamond bur increased postoperative sensitivity within 12 months. The presence of parafunctional habits and anxiety/depression may lead to postoperative sensitivity. CLINICAL SIGNIFICANCE: Roughening the sclerotic dentin with a diamond bur increased postoperative sensitivity within 12 months.


Asunto(s)
Resinas Compuestas , Dentina Secundaria , Humanos , Dentina , Estudios de Seguimiento , Ácido Edético , Restauración Dental Permanente , Recubrimientos Dentinarios , Dentina Secundaria/patología , Diamante
6.
Hum Mutat ; 42(3): 290-299, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33326660

RESUMEN

The current study aimed to identify new breast and/or ovarian cancer predisposition genes. For that, whole-exome sequencing (WES) was performed in the germline DNA of 52 non-BRCA1/BRCA2/TP53 mutation carrier women at high-risk for hereditary breast and ovarian cancer (HBOC). All variants were classified using information from population and disease specific databases, in silico prediction tools and the American College of Medical Genetics and Genomics (ACMG) criteria. Loss of heterozygosity (LOH) of tumor samples and segregation analyses were performed whenever possible. The variants identified were investigated in a second, independent cohort of 17 BC cases. Pathogenic/Likely Pathogenic variants were identified in known cancer genes such as CHEK2, MUTYH, PMS2, and RAD51C. Rare and potentially pathogenic variants were identified in DNA repair genes (FAN1, POLQ, and RAD54L) and other cancer-related genes such as DROSHA and SLC34A2. Interestingly, the variant c.149T>G in the FAN1 gene was identified in two unrelated families, and exhibited LOH in the tumor tissue of one of them. In conclusion, this is the largest Brazilian WES study involving families at high-risk for HBOC which has brought novel insights into the role of potentially new genetic risk factors for hereditary breast and ovarian cancer.


Asunto(s)
Neoplasias de la Mama , Síndrome de Cáncer de Mama y Ovario Hereditario , Neoplasias Ováricas , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/patología , Femenino , Genes BRCA2 , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Síndrome de Cáncer de Mama y Ovario Hereditario/genética , Humanos , Pérdida de Heterocigocidad , Mutación , Neoplasias Ováricas/genética , Secuenciación del Exoma
7.
Biol Reprod ; 105(2): 481-490, 2021 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-33982057

RESUMEN

The present study aimed to identify biomarkers to assess the quality of in vitro produced (IVP) bovine embryos in the culture media. IVP embryos on Day (D) 5 of development were transferred to individual drops, where they were maintained for the last 48 h of culture. Thereafter, the medium was collected and the embryos were transferred to the recipients. After pregnancy diagnosis, the media were grouped into the pregnant and nonpregnant groups. The metabolic profiles of the media were analyzed via electrospray ionization mass spectrometry, and the concentrations of pyruvate, lactate, and glutamate were assessed using fluorimetry. The spectrometric profile revealed that the media from embryos from the pregnant group presented a higher signal intensity compared to that of the nonpregnant group; the ions 156.13 Da [M + H]+, 444.33 Da [M + H]+, and 305.97 Da [M + H]+ were identified as biomarkers. Spent culture medium from expanded blastocysts (Bx) that established pregnancy had a greater concentration of pyruvate (p = 0.0174) and lesser concentration of lactate (p = 0.042) than spent culture medium from Bx that did not establish pregnancy. Moreover, pyruvate in the culture media of Bx can predict pregnancy with 90.9% sensitivity and 75% specificity. In conclusion, we identified markers in the culture media that helped in assessing the most viable IVP embryos with a greater potential to establish pregnancy.


Asunto(s)
Blastocisto/metabolismo , Bovinos/fisiología , Embrión de Mamíferos/química , Preñez/metabolismo , Animales , Biomarcadores , Medios de Cultivo/análisis , Femenino , Embarazo
8.
Mutagenesis ; 36(2): 177-185, 2021 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-33512444

RESUMEN

The present study aimed to evaluate the effect of the manool diterpene on genomic integrity. For this purpose, we evaluated the influence of manool on genotoxicity induced by mutagens with different mechanisms of action, as well as on colon carcinogenesis. The results showed that manool (0.5 and 1.0 µg/ml) significantly reduced the frequency of micronuclei induced by doxorubicin (DXR) and hydrogen peroxide in V79 cells but did not influence genotoxicity induced by etoposide. Mice receiving manool (1.25 mg/kg) exhibited a significant reduction (79.5%) in DXR-induced chromosomal damage. The higher doses of manool (5.0 and 20 mg/kg) did not influence the genotoxicity induced by DXR. The anticarcinogenic effect of manool (0.3125, 1.25 and 5.0 mg/kg) was also observed against preneoplastic lesions chemically induced in rat colon. A gradual increase in manool doses did not cause a proportional reduction of preneoplastic lesions, thus demonstrating the absence of a dose-response relationship. The analysis of serum biochemical indicators revealed the absence of hepatotoxicity and nephrotoxicity of treatments. To explore the chemopreventive mechanisms of manool via anti-inflammatory pathways, we evaluated its effect on nitric oxide (NO) production and on the expression of the NF-kB gene. At the highest concentration tested (4 µg/ml), manool significantly increased NO production when compared to the negative control. On the other hand, in the prophylactic treatment model, manool (0.5 and 1.0 µg/ml) was able to significantly reduce NO levels produced by macrophages stimulated with lipopolysaccharide. Analysis of NF-kB in hepatic and renal tissues of mice treated with manool and DXR revealed that the mutagen was unable to stimulate expression of the gene. In conclusion, manool possesses antigenotoxic and anticarcinogenic effects and its anti-inflammatory potential might be related, at least in part, to its chemopreventive activity.


Asunto(s)
Anticarcinógenos/farmacología , Neoplasias del Colon/tratamiento farmacológico , Daño del ADN/efectos de los fármacos , Diterpenos/farmacología , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Lesiones Precancerosas/tratamiento farmacológico , Animales , Anticarcinógenos/química , Línea Celular , Neoplasias del Colon/inducido químicamente , Cricetinae , Modelos Animales de Enfermedad , Diterpenos/química , Relación Dosis-Respuesta a Droga , Doxorrubicina/efectos adversos , Etopósido/efectos adversos , Peróxido de Hidrógeno/efectos adversos , Masculino , Ratones , Micronúcleos con Defecto Cromosómico/inducido químicamente , Pruebas de Micronúcleos , Pruebas de Mutagenicidad , Extractos Vegetales/farmacología , Lesiones Precancerosas/inducido químicamente , Ratas , Ratas Wistar , Salvia officinalis/química
9.
Anticancer Drugs ; 32(5): 567-574, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-33661189

RESUMEN

Immune checkpoint inhibitors were approved for advanced nonsmall cell lung cancer (NSCLC) treatment. Despite improved survival, not all patients benefit from these agents. Here, the prognostic impact of pretreatment modified Glasgow Prognostic Score (mGPS) and neutrophil-to-lymphocyte ratio (NLR) was assessed. From 77 patients included, 83.2% received at least one prior systemic therapy. Immune-related adverse events (irAE) occurred in 20 patients. A lower mGPS was associated with higher median overall survival (OS), and a lower Eastern Cooperative Oncology Group (ECOG), irAE and fewer metastatic sites with better survival. A trend towards greater OS and progression-free survival (PFS) was stated among patients with NLR <5. mGPS 0 was associated with better survival; ≥3 metastatic sites with worse PFS and OS; ECOG >2 with worse OS and irAE with better survival. Pretreatment mGPS seems to be useful for predicting survival among advanced NSCLC patients treated with anti-programmed cell death 1 drugs, with ECOG performance status, irAE occurrence, and number of metastatic sites acting as survival predictors.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Fumar Cigarrillos/epidemiología , Comorbilidad , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Mediadores de Inflamación/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Linfocitos/citología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neutrófilos/citología , Pronóstico , Índice de Severidad de la Enfermedad
10.
Pulm Pharmacol Ther ; 71: 102078, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34571094

RESUMEN

Actinomycosis is a rare chronic infection triggered by species of Actinomyces. Although thoracic involvement represents about 15% of human actinomycosis, its true incidence may be underestimated, not only because of its challenging diagnosis, but also because it can be treated unintentionally with antibiotics for other diseases. In this sense, this work aims at providing an up-to-date literature review on thoracic actinomycoses, with particular emphasis on presentation, diagnostic and therapeutic approaches, also paving upcoming clinical interventions from findings obtained of a presentation of a case series. Data discussed here clearly denote the rarity, non-specificity and heterogeneity of clinical presentations of the disease, reinforcing the need for individualized therapeutic approaches.


Asunto(s)
Actinomicosis , Bronquiectasia , Enfermedades Pulmonares , Actinomyces , Actinomicosis/diagnóstico , Actinomicosis/tratamiento farmacológico , Bronquiectasia/tratamiento farmacológico , Humanos , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/tratamiento farmacológico , Infección Persistente
11.
J Assist Reprod Genet ; 38(8): 2209-2217, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33866497

RESUMEN

PURPOSE: The aim of this study was to analyze the metabolic profiles of blastocoel fluid (BF) obtained from bovine embryos produced in vivo and in vitro. METHODS: Expanded blastocysts (20/group) that were in vitro and in vivo derived at day 7 were used. BF was collected and analyzed under direct infusion conditions using a microTOF-Q® mass spectrometer with electrospray ionization and a mass range of 50-650 m/z. RESULTS: The spectrometry showed an evident difference in the metabolic profiles of BF from in vivo and in vitro produced embryos. These differences were very consistent between the samples of each group suggesting that embryo fluids can be used to identify the origin of the embryo. Ions 453.15 m/z, 437.18 m/z, and 398.06 m/z were identified as biomarkers for the embryo's origin with 100% sensitivity and specificity. Although it was not possible to unveil the molecular identity of the differential ions, the resulting spectrometric profiles provide a phenotype capable of differentiating embryos and hence constitute a potential parameter for embryo selection. CONCLUSION: To the best of our knowledge, our results showed, for the first time, an evident difference between the spectrometric profiles of the BF from bovine embryos produced in vivo and in vitro.


Asunto(s)
Biomarcadores/análisis , Blastocisto/citología , Embrión de Mamíferos/citología , Líquido Intracelular/metabolismo , Metaboloma , Espectrometría de Masa por Ionización de Electrospray/métodos , Animales , Blastocisto/metabolismo , Bovinos , Embrión de Mamíferos/metabolismo , Femenino
12.
J Strength Cond Res ; 35(4): 1082-1088, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-30325790

RESUMEN

ABSTRACT: Andrade, DM, Fernandes, G, Miranda, R, Reis Coimbra, D, and Bara Filho, MG. Training load and recovery in volleyball during a competitive season. J Strength Cond Res 35(4): 1082-1088, 2021-The objective of this study was to analyze the training load (TL) and recovery status (RS) of a volleyball team in different periods of the season. Fifteen male athletes participated in the study. Training load was quantified through the rate of perceived exertion of session. The total weekly TL of the preparatory period (PP), competitive period I (CPI), and competitive period II (CPII) was calculated. Total quality recovery was used to evaluate the initial and final RS. Training load was higher (p < 0.05) in PP than in CPI and CPII. The final RS was lower (p < 0.05) in PP than in CPI and CPII. There was a difference (p < 0.05) between the initial and final RS in the analyzed periods. An inverse correlation (ρ: -0.62) was observed between the TL and the initial and final difference RS in PP. In conclusion, PP in volleyball presented the highest TL, related to a greater difference between the initial and final RS.


Asunto(s)
Voleibol , Atletas , Humanos , Masculino , Estaciones del Año
13.
BMC Cancer ; 20(1): 143, 2020 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-32087690

RESUMEN

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene expression regulation and have been described as key regulators of carcinogenesis. Aberrant miRNA expression has been frequently reported in sporadic breast cancers, but few studies have focused on profiling hereditary breast cancers. In this study, we aimed to identify specific miRNA signatures in hereditary breast tumors and to compare with sporadic breast cancer and normal breast tissues. METHODS: Global miRNA expression profiling using NanoString technology was performed on 43 hereditary breast tumors (15 BRCA1, 14 BRCA2, and 14 BRCAX), 23 sporadic breast tumors and 8 normal breast tissues. These normal breast tissues derived from BRCA1- and BRCA2- mutation carriers (n = 5) and non-mutation carriers (n = 3). Subsequently, we performed receiver operating characteristic (ROC) curve analyses to evaluate the diagnostic performance of differentially expressed miRNAs. Putative target genes of each miRNAs considered as potential biomarkers were identified using miRDIP platform and used for pathway enrichment analysis. RESULTS: miRNA expression analyses identified several profiles that were specific to hereditary breast cancers. A total of 25 miRNAs were found to be differentially expressed (fold change: > 2.0 and p < 0.05) and considered as potential biomarkers (area under the curve > 0.75) in hereditary breast tumors compared to normal breast tissues, with an expressive upregulation among BRCAX cases. Furthermore, bioinformatic analysis revealed that these miRNAs shared target genes involved in ErbB, FoxO, and PI3K-Akt signaling pathways. CONCLUSIONS: Our results showed that miRNA expression profiling can differentiate hereditary from sporadic breast tumors and normal breast tissues. These miRNAs were remarkably deregulated in BRCAX hereditary breast cancers. Therefore, miRNA signatures can be used as potential novel diagnostic biomarkers for the prediction of BRCA1/2- germline mutations and may be useful for future clinical management.


Asunto(s)
Proteína BRCA1/genética , Proteína BRCA2/genética , Biomarcadores de Tumor/genética , Neoplasias de la Mama/patología , Regulación Neoplásica de la Expresión Génica , Mutación de Línea Germinal , MicroARNs/genética , Adulto , Anciano , Brasil , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Persona de Mediana Edad , Curva ROC
14.
J Toxicol Environ Health A ; 83(21-22): 673-686, 2020 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-32886024

RESUMEN

Licochalcone A (LicoA) is a flavonoid derived from Glycyrrhiza spp. plants. The present study aimed to investigate the antioxidant, cytotoxic, genotoxic, and chemopreventive effects of LicoA in in vitro and in vivo systems. The results showed that LicoA (197.1 µM) scavenged 77.92% of free radicals. Concentrations of 147.75 µM or higher LicoA produced cytotoxicity in Chinese hamster ovary (CHO) fibroblasts. LicoA treatments of 4.43 to 10.34 µM did not exert genotoxic activity, but at 11.8 µM significantly lowered nuclear division indexes, compared to negative control, revealing cytotoxicity. Lower concentrations (1.85 to 7.39 µM) exhibited protective activity against chromosomal damage induced by doxorubicin (DXR) or methyl methanesulfonate (MMS) in CHO cells. LicoA exerted no marked influence on DXR-induced genotoxicity in mouse erythrocytes, but reduced pre-neoplastic lesions induced by 1,2-dimethylhydrazine (DMH) in rat colon at 3.12 to 50 mg/kg b.w. Biochemical markers and body weight indicated no apparent toxicity. These findings contribute to better understanding the mechanisms underlying LicoA-initiated activity as a promising chemopreventive compound. ABBREVIATIONS: AC, aberrant crypts; ACF, aberrant crypt foci; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BOD, biochemical oxygen demand; CHO, Chinese hamster ovary fibroblast; DMH, 1,2-dimethylhydrazine; DMSO, dimethyl sulfoxide; DPPH, 2,2-diphenyl-1-picrylhydrazyl; DXR, doxorubicin hydrochloride; EDTA, ethylenediaminetetraacetic acid; GA, gallic acid; LicoA, licochalcone A; MMS, methyl methanesulfonate; MNBC, micronucleated binucleated cells; MNPCE, micronucleated polychromatic erythrocyte; NCE, normochromatic erythrocyte; NDI, nuclear division index; PBS, phosphate-buffered saline; PCE, polychromatic erythrocyte; XTT, 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide.


Asunto(s)
Antioxidantes/farmacología , Chalconas/farmacología , Citotoxinas/farmacología , Mutágenos/farmacología , Sustancias Protectoras/farmacología , Animales , Masculino , Ratones
15.
Mol Ther ; 26(1): 199-207, 2018 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-28988712

RESUMEN

Repair and regeneration of inflammation-induced bone loss remains a clinical challenge. LL37, an antimicrobial peptide, plays critical roles in cell migration, cytokine production, apoptosis, and angiogenesis. Migration of stem cells to the affected site and promotion of vascularization are essential for tissue engineering therapy, including bone regeneration. However, it is largely unknown whether LL37 affects mesenchymal stem cell (MSC) behavior and bone morphogenetic protein 2 (BMP2)-mediated bone repair during the bone pathologic remodeling process. By performing in vitro and in vivo studies with MSCs and a lipopolysaccharide (LPS)-induced mouse calvarial osteolytic bone defect model, we found that LL37 significantly promotes cell differentiation, migration, and proliferation in both unmodified MSCs and BMP2 gene-modified MSCs. Additionally, LL37 inhibited LPS-induced osteoclast formation and bacterial activity in vitro. Furthermore, the combination of LL37 and BMP2 markedly promoted MSC-mediated angiogenesis and bone repair and regeneration in LPS-induced osteolytic defects in mouse calvaria. These findings demonstrate for the first time that LL37 can be a potential candidate drug for promoting osteogenesis and for inhibiting bacterial growth and osteoclastogenesis, and that the combination of BMP2 and LL37 is ideal for MSC-mediated bone regeneration, especially for inflammation-induced bone loss.


Asunto(s)
Péptidos Catiónicos Antimicrobianos/farmacología , Proteína Morfogenética Ósea 2/metabolismo , Regeneración Ósea , Células Madre Mesenquimatosas/metabolismo , Cráneo/fisiología , Animales , Biomarcadores , Proteína Morfogenética Ósea 2/farmacología , Diferenciación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Lipopolisacáridos , Ratones , Osteoclastos/metabolismo , Osteogénesis , Osteólisis
16.
J Oral Maxillofac Surg ; 77(5): 1031-1039, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30763527

RESUMEN

PURPOSE: The use of plates for open reduction and internal fixation of mandibular fractures has become a widely accepted method in the past 3 decades. However, the anterior mandible is well suited to lag screw fixation owing to the thickness of its bony cortices. Hence, the purpose of the present study was to comparatively evaluate clinical outcomes of fixation using lag screws and miniplates in anterior mandibular fractures. PATIENTS AND METHODS: Fifty patients reporting to the department of oral and maxillofacial surgery with noncomminuted anterior mandibular fractures were randomly divided into 2 groups of 25 patients each. Patients in group A were treated with 2.5-mm lag screws 22 to 26 mm in length and those in group B were treated with 2.0-mm 4-hole miniplates with a gap using monocortical screws. Subsequent follow-up was performed at 3, 6, 12, and 24 weeks postoperatively. The primary determinants included radiographic analysis of the fracture gap and biting efficiency of the patients in groups A and B. The secondary determinants included evaluation of duration of surgery, occlusion before and after injury, and postoperative complications. Results were evaluated using χ2 and unpaired t tests. RESULTS: The mean age of the patients in this study was 29.1 ± 8.32 years (range, 18 to 67 yr). The mean postoperative fracture gap was considerably larger in group B. The mean duration of surgery (minutes) was 37.60 ± 9.30 for group A and 47 ± 6.55 for group B. The difference was statistically significant (P = .001). The lag screw group showed faster improvement in biting efficiency compared with the miniplate group. CONCLUSIONS: Lag screw fixation was found to have good stability and rigidity, was inexpensive, and was less time consuming in treating anterior mandibular fractures compared with miniplates.


Asunto(s)
Fracturas Mandibulares , Adolescente , Adulto , Anciano , Placas Óseas , Tornillos Óseos , Fijación Interna de Fracturas , Humanos , Fracturas Mandibulares/cirugía , Persona de Mediana Edad , Titanio , Resultado del Tratamiento , Adulto Joven
17.
J Mater Sci Mater Med ; 30(9): 105, 2019 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-31494718

RESUMEN

Bioactive glasses (BG) are known for their ability to bond to bone tissue. However, in critical situations, even the osteogenic properties of BG may be not enough to induce bone consolidation. Thus, the enrichment of BG with polymers such as Poly (D, L-lactic-co-glycolic) acid (PLGA) and associated to photobiomodulation (PBM) may be a promising strategy to promote bone tissue healing. The aim of the present study was to investigate the in vivo performance of PLGA supplemented BG, associated to PBM therapy, using an experimental model of cranial bone defect in rats. Rats were distributed in 4 different groups (Bioglass, Bioglass/PBM, Bioglas/PLGA and BG/PLGA/PBM). After the surgical procedure to induce cranial bone defects, the pre-set samples were implanted and PBM treatment (low-level laser therapy) started (808 nm, 100 mW, 30 J/cm2). After 2 and 6 weeks, animals were euthanized, and the samples were retrieved for the histopathological, histomorphometric, picrosirius red staining and immunohistochemistry analysis. At 2 weeks post-surgery, it was observed granulation tissue and areas of newly formed bone in all experimental groups. At 6 weeks post-surgery, BG/PLGA (with or without PBM) more mature tissue around the biomaterial particles. Furthermore, there was a higher deposition of collagen for BG/PLGA in comparison with BG/PLGA/PBM, at second time-point. Histomorphometric analysis demonstrated higher values of BM.V/TV for BG compared to BG/PLGA (2 weeks post-surgery) and N.Ob/T.Ar for BG/PLGA compared to BG and BG/PBM (6 weeks post-surgery). This current study concluded that the use of BG/PLGA composites, associated or not to PBM, is a promising strategy for bone tissue engineering.


Asunto(s)
Sustitutos de Huesos/uso terapéutico , Cerámica/uso terapéutico , Fracturas Óseas/terapia , Luz , Ácido Poliglicólico/uso terapéutico , Cráneo/lesiones , Cicatrización de Heridas/efectos de los fármacos , Animales , Sustitutos de Huesos/química , Sustitutos de Huesos/efectos de la radiación , Trasplante Óseo/métodos , Cementación/métodos , Cerámica/química , Terapia Combinada , Masculino , Ensayo de Materiales , Osteogénesis/efectos de los fármacos , Osteogénesis/efectos de la radiación , Fototerapia/métodos , Ácido Poliglicólico/química , Ratas , Ratas Wistar , Cráneo/efectos de los fármacos , Cráneo/efectos de la radiación , Ingeniería de Tejidos
18.
Genet Mol Biol ; 42(1): 145-150, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30856245

RESUMEN

The filter cake from sugar cane processing is rich in organic matter and nutrients, which favors the proliferation of microorganisms with potential to deconstruct plant biomass. From the metagenomic data of this material, we assembled a draft genome that was phylogenetically related to Thermomonospora curvata DSM 43183, which shows the functional and ecological importance of this bacterium in the filter cake. Thermomonospora is a gram-positive bacterium that produces cellulases in compost, and it can survive temperatures of 60 ºC. We identified a complete set of biomass depolymerizing enzymes in the draft genome of Thermomonospora sp. CIT 1, such as α-amylase, catalase-peroxidases, ß-mannanase, and arabinanase, demonstrating the potential of this bacterium to deconstruct the components of starch, lignin, and hemicellulose. In addition, the draft genome of Thermomonospora sp. CIT 1 contains 18 genes that do not share identity with five other species of Thermomonospora, suggesting that this bacterium has different genetic characteristics than those present in genomes reported so far for this genus. These findings add a new dimension to the current understanding of the functional profile of this microorganism that inhabits agro-industrial waste, which may boost new gene discoveries and be of importance for application in the production of bioethanol.

19.
J Oral Implantol ; 45(4): 274-280, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31216254

RESUMEN

Strontium is a naturally occurring alkaline earth metal that has been shown to be useful not only in the treatment and prevention of osteoporosis but also in the treatment of dentinal hypersensitivity in the oral cavity; strontium is also an effective cariostatic, antiplaque, antigingivitis agent. Relatively little is known, however, about the effects of strontium on gingival fibroblasts. The purpose of the present investigation was to conduct in vitro studies on the potential for strontium to positively affect the activity of these cells such that it might be effective in the enhancement of gingival attachment to surfaces, such as healing abutments in implants in the oral cavity. The results indicate that strontium added as strontium citrate (0.5-1.0 mM), both in the absence and presence of a healing abutment, increases human gingival cell activity and decreases apoptosis in these cells. Scanning electron microscopy studies also reveal that the addition of strontium increases attachment of gingival fibroblasts to the surfaces of healing abutments. These studies provide the basis for further investigations on the use of strontium in the prevention and treatment of peri-implantitis by maximizing the formation of a peri-implant soft-tissue barrier.


Asunto(s)
Pilares Dentales , Encía , Estroncio , Fibroblastos/efectos de los fármacos , Encía/efectos de los fármacos , Humanos , Estroncio/farmacología , Propiedades de Superficie , Titanio
20.
Indian J Microbiol ; 59(2): 147-153, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31031428

RESUMEN

Nanocomposites containing antimicrobial agents and calcium phosphates have been developed. Thus, this study assessed the effects of two compounds containing silver nanoparticles (AgNPs) and ß-calcium glycerophosphate (CaGP), associated or not with tyrosol (TYR), against planktonic cells and biofilms of Candida albicans and Streptococcus mutans. The nanocompounds were synthesized through chemical and 'green' processes and characterized by scanning electron microscopy. The minimum and fractional inhibitory concentrations of each compound were determined for planktonic cells. Next, 24-h single biofilms of C. albicans and S. mutans were treated for 24 h with the nanocompounds alone or in combination with TYR, and the antibiofilm effect was assessed through enumeration of colony forming units. Biofilm data were statistically examined using one-way ANOVA and the Kruskal-Wallis test (α = 0.05). The chemically synthesized nanocompound in combination with TYR demonstrated a synergistic effect against planktonic cells of C. albicans and S. mutans. For the nanocompound obtained through the 'green' route associated with TYR, a synergistic effect was observed only against C. albicans. For biofilms, only the combination obtained through the 'green' route + TYR demonstrated a synergistic effect against C. albicans. Our results may contribute to the development of oral care products containing AgNPs-CaGP and TYR to combat oral infections.

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