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Acacia aroma, native plant from San Luis, Argentina, is commonly used as antiseptic and for healing of wounds. The present study was conducted to investigate the in vitro cytotoxicity and genotoxicity of hot aqueous extract (HAE) and ethanolic extract (EE) of A. aroma.The cytotoxic activity was assayed by neutral red uptake assay on Vero cell. Cell treatment with a range from 100 to 5000 μg/mL of HAE and EE showed that 500 μg/mL and 100 μg/mL were the maximum noncytotoxic concentrations, respectively. The CC50 was 658 μg/mL for EE and 1020 μg/mL for HAE.The genotoxicity was tested by the single-cell gel electrophoresis comet assay. The results obtained in the evaluation of DNA cellular damage exposed to varied concentrations of the HAE showed no significant genotoxic effect at range of 1–20mg/mL. The EE at 20mg/mL showed moderate genotoxic effect related to the increase of the DNA percentage contained in tail of the comet; DNA was classified in category 2. At concentrations below 5mg/mL, the results of cytotoxicity and genotoxicity of aqueous and ethanolic extracts of Acacia aroma guarantee the safety at cell and genomic level. However further studies are needed for longer periods including animal models to confirm the findings. [ABSTRACT FROM AUTHOR]

Regenerative techniques are increasingly applied in endodontic surgery, but different materials may have varying impacts on soft and hard tissue healing. This systematic review aims to evaluate the effectiveness of autologous platelet concentrates (APCs) in clinical and radiographic healing after endodontic surgery. The data for this systematic review were processed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for improving the reporting of systematic reviews and meta-analyses. A literature search was conducted until October 2023 on PubMed, Scopus, and Cochrane Databases. Randomized controlled trials and controlled clinical trials addressing the use of APCs in patients who presented persistent periapical lesions and needed periapical surgery were included. Dual publications, narrative reviews, systematic reviews, case series, questionnaires, animal studies, case reports, letters to the editor, in vitro studies, and abstracts were excluded. In total, the search resulted in 14 papers. Clinical and radiographical findings were reported, showing that when APCs were used, patients exhibited less pain and swelling and a greater reduction of apical radiolucency after 12 months follow-up on average. However, the moderate/high risk of bias of included studies and their high heterogeneity, do not allow one to draw definitive conclusions on the effectiveness of APC after endodontic surgery.

Chromosomal rearrangements are important drivers in cancer, and their robust detection is essential for diagnosis, prognosis, and treatment selection, particularly for bone and soft tissue tumors. Current diagnostic methods are hindered by limitations, including difficulties with multiplexing targets and poor quality of RNA. A novel targeted DNA-based next-generation sequencing method, formalin-fixed, paraffin-embedded-targeted locus capture (FFPE-TLC), has shown advantages over current diagnostic methods when applied on FFPE lymphomas, including the ability to detect novel rearrangements. We evaluated the utility of FFPE-TLC in bone and soft tissue tumor diagnostics. FFPE-TLC sequencing was successfully applied on noncalcified and decalcified FFPE samples (n = 44) and control samples (n = 19). In total, 58 rearrangements were identified in 40 FFPE tumor samples, including three previously negative samples, and none was identified in the FFPE control samples. In all five discordant cases, FFPE-TLC could identify gene fusions where other methods had failed due to either detection limits or poor sample quality. FFPE-TLC achieved a high specificity and sensitivity (no false positives and negatives). These results indicate that FFPE-TLC is applicable in cancer diagnostics to simultaneously analyze many genes for their involvement in gene fusions. Similar to the observation in lymphomas, FFPE-TLC is a good DNA-based alternative to the conventional methods for detection of rearrangements in bone and soft tissue tumors., (Copyright © 2023 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Dental anxiety is a crucial problem for dentistry because it may represent a significant risk to oral health. Within the framework of the Cognitive Vulnerability Model (CVM), which sheds light on the cognitive vulnerability patterns that may cause dental anxiety, this study aimed to assess the psychometric characteristics of the Italian version of the Dental Fear Maintenance Questionnaire (DFMQ). The DFMQ is a 32-item questionnaire that assesses four cognitive vulnerability patterns, i.e., dangerousness, disgust, unpredictability, and uncontrollability. In a sample of 200 dental patients who had accessed public-university-hospital dental surgery, this study assessed the model fit of the DFMQ and different types of validity (i.e., predictive, convergent, construct, and discriminant validity). In addition, potential differences between DFMQ dimensions were assessed based on gender (men vs. women) and age ranges. All indicators of cognitive vulnerability were significantly associated with high dental anxiety when each variable was included independently. In contrast, when the DFMQ subscales were considered together, only unpredictability and uncontrollability were found to be associated with high dental anxiety. Women had higher scores for unpredictability, uncontrollability, and general dangerousness than men. In addition, older patients had higher scores for some vulnerability cognitive patterns than younger patients. This study provides Italian dentists and researchers with a valid questionnaire to assess cognitive factors associated with dental anxiety.

Fibroblast growth factor receptors (FGFRs) 1-4 are involved in prostate cancer (PCa) regulation, but the role of FGFR-like 1 (FGFRL1) in PCa is unclear. FGFRL1 expression was studied by qRT-PCR and immunohistochemistry of patient tissue microarrays (TMAs) and correlated with clinical patient data. The effects of FGFRL1 knockdown (KD) in PC3M were studied in in vitro culture models and in mouse xenograft tumors. Our results showed that FGFRL1 was significantly upregulated in PCa. The level of membranous FGFRL1 was negatively associated with high Gleason scores (GSs) and Ki67, while increased cytoplasmic and nuclear FGFRL1 showed a positive correlation. Cox regression analysis indicated that nuclear FGFRL1 was an independent prognostic marker for biochemical recurrence after radical prostatectomy. Functional studies indicated that FGFRL1-KD in PC3M cells increases FGFR signaling, whereas FGFRL1 overexpression attenuates it, supporting decoy receptor actions of membrane-localized FGFRL1. In accordance with clinical data, FGFRL1-KD markedly suppressed PC3M xenograft growth. Transcriptomics of FGFRL1-KD cells and xenografts revealed major changes in genes regulating differentiation, ECM turnover, and tumor-stromal interactions associated with decreased growth in FGFRL1-KD xenografts. Our results suggest that FGFRL1 upregulation and altered cellular compartmentalization contribute to PCa progression. The nuclear FGFRL1 could serve as a prognostic marker for PCa patients.

Background: Prostate cancer (PCa) is the second most common tumour diagnosed in men. Tumoral heterogeneity in PCa creates a significant challenge to develop robust prognostic markers and novel targets for therapy. An analysis of gene regulatory networks (GRNs) in PCa may provide insight into progressive PCa. Herein, we exploited a graph-based enrichment score to integrate data from GRNs identified in preclinical prostate orthografts and differentially expressed genes in clinical resected PCa. We identified active regulons (transcriptional regulators and their targeted genes) associated with PCa recurrence following radical prostatectomy., Methods: The expression of known transcription factors and co-factors was analysed in a panel of prostate orthografts ( n = 18). We searched for genes (as part of individual GRNs) predicted to be regulated by the highest number of transcriptional factors. Using differentially expressed gene analysis (on a per sample basis) coupled with gene graph enrichment analysis, we identified candidate genes and associated GRNs in PCa within the UTA cohort, with the most enriched regulon being JMJD6, which was further validated in two additional cohorts, namely EMC and ICGC cohorts. Cox regression analysis was performed to evaluate the association of the JMJD6 regulon activity with disease-free survival time in the three clinical cohorts as well as compared to three published prognostic gene signatures (TMCC11, BROMO-10 and HYPOXIA-28)., Results: 1308 regulons were correlated to transcriptomic data from the three clinical prostatectomy cohorts. The JMJD6 regulon was identified as the top enriched regulon in the UTA cohort and again validated in the EMC cohort as the top-ranking regulon. In both UTA and EMC cohorts, the JMJD6 regulon was significantly associated with cancer recurrence. Active JMJD6 regulon also correlated with disease recurrence in the ICGC cohort. Furthermore, Kaplan-Meier analysis confirmed shorter time to recurrence in patients with active JMJD6 regulon for all three clinical cohorts (UTA, EMC and ICGC), which was not the case for three published prognostic gene signatures (TMCC11, BROMO-10 and HYPOXIA-28). In multivariate analysis, the JMJD6 regulon status significantly predicted disease recurrence in the UTA and EMC, but not ICGC datasets, while none of the three published signatures significantly prognosticate for cancer recurrence., Conclusions: We have characterised gene regulatory networks from preclinical prostate orthografts and applied transcriptomic data from three clinical cohorts to evaluate the prognostic potential of the JMJD6 regulon.

Stone Handling (SH) is a solitary object play behaviour that can vary from simple exploratory actions to more complex manipulations. So far, among primates, this behaviour has been exclusively reported in macaques. We collected data on 62 geladas (Theropithecus gelada) housed at the NaturZoo (Rheine, Germany). We found that about 70% of subjects belonging to all age- and sex-classes engaged in SH. Due to their exceptional manipulative skills (the highest opposability index among nonhuman primates) and propensity to play, geladas are a good model species to test hypotheses on the function of this form of object play. While the frequency of SH tended to decrease with age of the player, the duration of each session and its complexity tended to increase in juveniles/subadults and adults compared to infants. This age-related variation in terms of frequency, duration and complexity suggests that, in agreement with the motor training hypothesis, SH could have a role in the neural-motor development of immature subjects and a basic function in stimulating neurogenesis and maintaining the psychological well-being of adults. In all age classes, the frequency of SH did not vary across pre-feeding, feeding and non-feeding conditions. Hence, our data do not support the misdirected foraging hypothesis, which predicts that animals engage in SH to anticipate food provisioning. In conclusion, our study reveals, for the first time, the presence of SH outside the genus Macaca and attempts to delineate possible functions of the behaviour in geladas. Since the hypotheses tested cannot be mutually exclusive, long-term studies of SH across individuals' lifetimes in both captive and wild groups of geladas are needed to clarify the proximate and ultimate functions of the behaviour in this species of Papionini. Finally, long-term studies could also provide some important indications about the cultural nature and social transmission of SH in a taxonomic group outside the Macaca genus., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Neurofibromatosis type 1 (NF1) is a common tumor predisposition syndrome in which glioma is one of the prevalent tumors. Gliomagenesis in NF1 results in a heterogeneous spectrum of low- to high-grade neoplasms occurring during the entire lifespan of patients. The pattern of genetic and epigenetic alterations of glioma that develops in NF1 patients and the similarities with sporadic glioma remain unknown. Here, we present the molecular landscape of low- and high-grade gliomas in patients affected by NF1 (NF1-glioma). We found that the predisposing germline mutation of the NF1 gene was frequently converted to homozygosity and the somatic mutational load of NF1-glioma was influenced by age and grade. High-grade tumors harbored genetic alterations of TP53 and CDKN2A, frequent mutations of ATRX associated with Alternative Lengthening of Telomere, and were enriched in genetic alterations of transcription/chromatin regulation and PI3 kinase pathways. Low-grade tumors exhibited fewer mutations that were over-represented in genes of the MAP kinase pathway. Approximately 50% of low-grade NF1-gliomas displayed an immune signature, T lymphocyte infiltrates, and increased neo-antigen load. DNA methylation assigned NF1-glioma to LGm6, a poorly defined Isocitrate Dehydrogenase 1 wild-type subgroup enriched with ATRX mutations. Thus, the profiling of NF1-glioma defined a distinct landscape that recapitulates a subset of sporadic tumors.

Opioid addiction rates are at a national high, with significant morbidity and mortality. In women, rates have been steadily increasing to be at par with addiction rates in men. Women tend to have quicker addiction and shorter duration to adverse outcomes. Treatment of women has the best outcomes when it is gender-specific, trauma-informed, connected with access to psychiatric services, and integrated into the medical home. Improved outcomes can be achieved with coordinated systems of care based on the harm-reduction model, with integration of medication-assisted therapy in a patient-centered medical home., (Published by Elsevier Inc.)

Acacia aroma, native plant from San Luis, Argentina, is commonly used as antiseptic and for healing of wounds. The present study was conducted to investigate the in vitro cytotoxicity and genotoxicity of hot aqueous extract (HAE) and ethanolic extract (EE) of A. aroma. The cytotoxic activity was assayed by neutral red uptake assay on Vero cell. Cell treatment with a range from 100 to 5000 μg/mL of HAE and EE showed that 500 μg/mL and 100 μg/mL were the maximum noncytotoxic concentrations, respectively. The CC50 was 658 μg/mL for EE and 1020 μg/mL for HAE. The genotoxicity was tested by the single-cell gel electrophoresis comet assay. The results obtained in the evaluation of DNA cellular damage exposed to varied concentrations of the HAE showed no significant genotoxic effect at range of 1-20 mg/mL. The EE at 20 mg/mL showed moderate genotoxic effect related to the increase of the DNA percentage contained in tail of the comet; DNA was classified in category 2. At concentrations below 5 mg/mL, the results of cytotoxicity and genotoxicity of aqueous and ethanolic extracts of Acacia aroma guarantee the safety at cell and genomic level. However further studies are needed for longer periods including animal models to confirm the findings.

The estrogenic potential of 4-nonylphenol (4-NP), 4-octylphenol (4-OP), p-t-octylphenol (p-t-OP) and three trace elements, lead (Pb), copper (Cu) and cadmium (Cd(NO(3))(2) and CdCl(2)), were compared in two different tests, a proliferation assay with estrogen receptor-positive human MCF-7 breast cancer cells (E-screen) and the induction of vitellogenin (Vtg) in juvenile goldfish (Carassius auratus). The results showed differences in the bioassays' sensitivity and potency with the following order: E-screen>Vtg. Among alkylphenols, both in vitro and in vivo, 4-NP and 4-OP showed the highest estrogen-like activity while p-t-OP was inferior. For trace elements, Pb and Cu showed estrogenic activity in vitro and they were also active in vivo. A range of estrogenicity was observed for different species of cadmium (Cd(NO(3))(2) and CdCl(2)) which showed the highest relative proliferative effect (RPE %) in vitro, when compared with the 17beta-estradiol (E(2); RPE=100%) but, Cd(NO(3))(2) was not estrogenic in vivo. The results suggest that an integrated approach using in vitro and in vivo assays is necessary for a correct risk assessment of the endocrine disrupting activity induced by environmental contaminants., (Copyright 2010 Elsevier Inc. All rights reserved.)

In the last years pharmaceuticals have aroused great interest as environmental pollutants for their toxic effects towards non target organisms. This study wants to draw attention to a further adverse effect of drugs, the endocrine interference. The most representative drugs of the widespread classes in environment were investigated. The YES-test and the E-screen assay were performed to detect the capability of these substances to bind the human estrogenic receptor alpha (hER alpha) in comparison with 17beta-estradiol. Out of 14 tested pharmaceuticals, 9 were positive to YES-assay and 11 were positive to E-screen assay; in particular, Furosemide and the fibrates (Bezafibrate, Fenofibrate and Gemfibrozil) gave the maximal estrogenic response. Tamoxifen showed its dual activity as agonist and antagonist of hER alpha.