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The use of a higher dose per fraction to overcome the high radioresistance of prostate cancer cells has been unsuccessfully proposed. Herein, we present PC3 and DU-145, castration-resistant prostate cancer cell lines that survived a clinically used ultra-higher dose per fraction, namely, radioresistant PC3 and DU-145 cells (PC3RR and DU-145RR). Compared to PC3, PC3RR showed a higher level of aggressive behaviour, with enhanced clonogenic potential, DNA damage repair, migration ability and cancer stem cell features. Furthermore, compared to PC3, PC3RR more efficiently survived further radiation by increasing proliferation and down-regulating pro-apoptotic proteins. No significant changes of the above parameters were described in DU-145RR, suggesting that different prostate cancer cell lines that survive ultra-higher dose per fraction do not display the same grade of aggressive phenotype. Furthermore, both PC3RR and DU-145RR increased antioxidant enzymes and mesenchymal markers. Our data suggest that different molecular mechanisms could be potential targets for future treatments plans based on sequential strategies and synergistic effects of different modalities, possibly in a patient-tailored fashion. Moreover, PC3RR cells displayed an increase in specific markers involved in bone remodeling, indicating that radiotherapy selects a PC3 population capable of migrating to secondary metastatic sites. Finally, PC3RR cells showed a better sensitivity to Docetaxel as compared to native PC3 cells. This suggests that a subset of patients with castration-resistant metastatic disease could benefit from upfront Docetaxel treatment after the failure of radiotherapy.

Objective: Bone metastasis is a clinically important outcome of prostate carcinoma (PC). We focused on the phenotypic and functional characterization of a particularly aggressive phenotype within the androgen-independent bone metastasis-derived PC3 cell line. These cells, originated from the spontaneous conversion of a CD44-negative subpopulation, stably express the CD44v8-10 isoform (CD44v8-10 pos ) and display stem cell-like features and a marked invasive phenotype in vitro that is lost upon CD44v8-10 silencing., Methods: Flow cytometry, enzyme-linked immunoassay, immunofluorescence, and Western blot were used for phenotypic and immunologic characterization. Real-time quantitative polymerase chain reaction and functional assays were used to assess osteomimicry., Results: Analysis of epithelial-mesenchymal transition markers showed that CD44v8-10 pos PC3 cells surprisingly display epithelial phenotype and can undergo osteomimicry, acquiring bone cell phenotypic and behavioral traits. Use of specific siRNA evidenced the ability of CD44v8-10 variant to confer osteomimetic features, hence the potential to form bone-specific metastasis. Moreover, the ability of tumors to activate immunosuppressive mechanisms which counteract effective immune responses is a sign of the aggressiveness of a tumor. Here we report that CD44v8-10 pos cells express programmed death ligand 1, a negative regulator of anticancer immunity, and secrete exceptionally high amounts of interleukin-6, favoring osteoclastogenesis and immunosuppression in bone microenvironment. Notably, we identified a novel pathway activated by CD44v8-10, involving tafazzin (TAZ) and likely the Wnt/TAZ axis, known to play a role in upregulating osteomimetic genes., Conclusions: CD44v8-10 could represent a marker of a more aggressive bone metastatic PC population exerting a driver role in osteomimicry in bone. A novel link between TAZ and CD44v8-10 is also shown., Competing Interests: No potential conflicts of interest are disclosed., (Copyright © 2021 Cancer Biology & Medicine.)

Two grades of recycled wood (Waste Wood A and Waste Wood B) were fractionated on a pilot scale (800 BD kg) to monomeric sugars, lignin and lignosulfonates using SO 2 -Ethanol-Water (AVAP®) technology, including pretreatment, separation of cellulosic and hemicellulosic streams, and saccharification. Carbohydrate mass balance was obtained through determination of poly-, oligo- and monosaccharides as well as sugar degradation products in process streams. High monosaccharide yields were obtained confirming laboratory scale findings. Fermentability of mixed cellulosic and hemicellulosic sugar stream was confirmed on bench scale (25 kg)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Recycled wood of two grades (A and B) and spruce were converted on bench (100 o.d. g) and pilot (100 o.d. kg) scales to monosugars, lignin and lignosulfonates using SO 2 -Ethanol-Water (AVAP®) technology. After digestion, C6 and C5 sugars were recovered at 98-100% and 87-99% for Wood A and Spruce, respectively, while the values for Wood B were 92% and 74-87%. Cellulose was hydrolysed to glucose at 90% or higher using enzyme charge of 7.1 FPU/g glucan. Hemicellulosic sugars were autohydrolyzed to 95-100% monosugars. At bench scale, monosaccharide yield was 609, 561 and 688 kg (hydrous) per BDT biomass for Wood A, Wood B and Spruce, respectively. Corresponding water insoluble lignin yield was 157, 148 and 189 kg per BDT biomass. The preliminary techno-economic evaluation revealed that conversion of recycled wood to sugars using AVAP® fractionation platform results in higher profitability in comparison to virgin wood., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019. Published by Elsevier Ltd.)

Altered regulation of copper (Cu) homeostasis may contribute to the development of many pathologies, such as metabolic, cardiovascular, neurodegenerative and cancerous diseases. Cu serum concentrations are strictly related to oxidative stress. During the past decade, it has been well demonstrated that even marginal deficits of this element contribute to development and progression of a number of chronic diseases. On the other hand, an excess of Cu may become a potent oxidant causing the generation of reactive oxygen species (ROS) and leading to the formation of macromolecules dangerous to health. In this review we will describe several chronic inflammatory diseases pathogenically related to the alteration of serum copper levels. Some considerations on present and future perspectives for use of natural antioxidants as effective drugs for the treatment of chronic diseases will be made to shed a glimmer of light on some of the mechanisms employed by natural antioxidants in controlling the distribution and concentration of biometals.

Oleuropein (Ole) is one of the most plentiful phenolic compounds with antioxidant, anti-inflammatory, anti-atherogenic, hypoglycemic and hypolipidemic effects. The aim of our study was to establish whether the positive Ole-related effects on liver steatosis could be associated with autophagy. Female and male C57BL/6J mice were fed normal diet (ND) or high-fat diet (HFD) for eight weeks, and Ole was added or not for the following eight weeks. The autophagy-related proteins Akt, mTOR, AMPK, ULK1, Beclin-1, LC3B and p62/Sqstm1 were analyzed. Interestingly, Ole induced a different regulation of the Akt/mTOR pathway in female compared to male mice, but was able to activate the autophagic process in ND and HFD mice through AMPK-dependent phosphorylation of ULK1 at Ser555, regardless of the gender. Our work reveals the ability of Ole to induce, in liver of ND and HFD mice, autophagy independently by gender-specific mTOR activation. We highlight Ole as a novel therapeutic approach to counteract unhealthy diet-related liver steatosis by targeting autophagy.

Background/aims: No comprehensive assessment of the influence of the home environment on traumatic dental injuries (TDI) has been conducted to date. The aim of this study was to explore the relationship between family environment and TDI among adolescents from East London., Materials and Methods: This cross-sectional study used data from 646 adolescents who participated in phase III of the Research with East London Adolescents Community Health Survey (RELACHS). Family environment was measured with four indicators (non-nuclear family, discordant parental relationship and levels of parental support and parental punishment) measured through a self-administered questionnaire. Clinical examinations were performed for TDI, overjet and lip coverage. Logistic regression was used to test the crude and adjusted (controlling for sociodemographic and clinical factors) association of each family environment characteristic with TDI prevalence., Results: Twenty-nine percent of adolescents were from non-nuclear families, and 52.3% reported a discordant parental relationship. The mean score for parental support was -0.01 (SD: 0.90, range: -0.11 to 0.08), and the mean parental punishment score was 0.03 (SD: 0.86, range: -0.04 to 0.10). Adolescents from non-nuclear families had 1.63 (95% confidence interval: 1.06-2.53) greater odds of having TDI than those from nuclear families. However, this association was fully attenuated after adjusting for sociodemographic and clinical factors. The other three indicators of family environment were not associated with TDI either in crude or adjusted regression models., Conclusion: This study found weak evidence of an association between family environment and TDI., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: A priori registration of systematic review protocols in international prospective register of systematic reviews (PROSPERO) can help reduce selective reporting of outcomes. The aim of this study was to assess the association between registration of orthodontic systematic reviews in PROSPERO and review quality with the Assessment of Multiple Systematic Reviews (AMSTAR) tool., Study Design and Setting: Seven databases were searched for systematic reviews with/without meta-analysis in orthodontics published between 2012 and 2016. After duplicate study selection and data extraction, the quality of identified reviews was assessed in duplicate with the AMSTAR tool. Descriptive statistics of medians and interquartile ranges (IQRs) and chi-square/Fisher exact tests were calculated. Univariable/multivariable linear regression modeling was implemented to assess the effect of review registration on %AMSTAR score at α of 5%., Results: A total of 182 orthodontic systematic reviews were identified, 37 (20.3%) of which were registered. Considerable differences were seen in AMSTAR between registered (median = 86.4%; IQR = 77.3-95.5%) and nonregistered reviews (median = 72.7%; IQR = 59.1-81.8%). After adjustment, registration in PROSPERO was associated with an average increase in %AMSTAR score of 6.6% (95% confidence interval = 1.0-12.3%)., Conclusion: Although only a small percentage of orthodontic systematic reviews was registered a priori in PROSPERO, registered reviews were of higher quality than nonregistered reviews., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Aim of this study was to assess the registration of orthodontic systematic reviews in PROSPERO., Method: Seven databases were searched for orthodontic systematic reviews published in 2012-2016. After duplicate study selection and data extraction, descriptive statistics, followed by chi-square/Fisher exact tests were calculated. Finally, bivariable/multivariable regression with relative risks (RR) and 95% confidence intervals (CIs) was used., Results: A total of 182 orthodontic systematic reviews were identified, 37 (20.3%) of which were registered in PROSPERO, with registration rates ranging from 4.3% in 2012 to 37.0% in 2016. Differences in review registration were found according to publication year, geographic origin, multicentre status, funding, and journal category. After controlling for confounders, each additional year was associated with increased registration probability (RR = 1.51; 95% CI = 1.19-1.93). Reviews from South America were more likely to be registered than reviews from Europe (RR = 1.49; 95% CI = 1.06-2.11). Finally, reviews published in orthodontic specialty journals were more likely to be registered than reviews in general dentistry journals (RR = 1.87; 95% CI = 1.02-3.49)., Conclusions: A small percentage of orthodontic systematic reviews was registered a priori, although improvement signs have been seen since the initiation of PROSPERO.

Data on susceptibility of Haemophilus influenzae are scanty in Italy. We compared the activity of loracarbef (Ly 163892), a new carbacephem, with that of 4 other agents against 265 strains of H. influenzae (46 type b, 219 nontypable) isolated from adults and children at Istituti Clinici di Perfezionamento of Milano, between 1/1/84 and 1/1/89, and also from 7 children at pediatric departments in Lombardy during 1988. In adults 72 strains were all isolated from sputum of patients with pneumonia or chronic bronchitis; in children 199 strains were isolated from conjunctiva (53% of the patients had also a concomitant respiratory infection), 24 from middle ear, 18 from sputum and 32 from blood or cerebrospinal fluid. Minimal inhibiting concentrations (MIC) were determined by the broth microdilution technique. The incidence of resistance of H. influenzae to ampicillin was 3.8%; the lowest percentage of resistance was found for loracarbef (0%) and the highest for erythromycin (94% for strains isolated from children and 97% for strains isolated from adults).