A molecular characterization of the main phytochemicals and antioxidant activity of
(OR) fruit extract was carried out, as well as an evaluation of its hepatoprotective effect against diclofenac ...(DF)-induced acute liver injury was evaluated. Phenols, flavonoids and betalains were quantified, and antioxidant characterization was performed by means of the ABTS
, DPPH and FRAP assays. UPLC-QTOF-MS/MS was used to identify the main biocompounds present in OR fruit extract was carried out via. In the in vivo model, groups of rats were treated prophylactically with the OR fruit extract, betanin and
-acteylcysteine followed by a single dose of DF. Biochemical markers of oxidative stress (MDA and GSH) and relative gene expression of the inducible antioxidant response (
,
,
,
and
), cell death (
) and DNA repair (
) were analyzed. Western blot analysis was performed to measure protein levels of Nrf2 and immunohistochemical analysis was used to assess caspase-3 activity in the experimental groups. In our study, the OR fruit extract showed strong antioxidant and cytoprotective capacity due to the presence of bioactive compounds, such as betalain and phenols. We conclude that OR fruit extract or selected components can be used clinically to support patients with acute liver injury.
To investigate whether the target-isocenter deviations reported by a conventional Winston-Lutz (WL) test actually reflect the shifts of the measured prescription isodose line with respect to the ...target.
A conventional WL test uses a metallic ball as a target that aims at several fields. But this test does not report information on the accuracy of the delivery in terms of dose.
A conventional WL test using a metallic pointer as a target (Pointer-WL test) has been recreated in the Eclipse treatment planning system over an acrylic phantom containing a radiochromic film (Dose-WL test). After Dose-WL test delivery, the shift of the 80% prescription isodose line with respect to the target center (d80%-center) was measured using film dosimetry. The Pointer-WL and Dose-WL tests were performed in 10 different sessions. The isocenter deviation reported by the Pointer-WL test was compared to the d80%-center vector, according to the three patient's directions (Left–Right or LR; Anterior–Posterior or AP; and Superior–Inferior or SI).
The deviations (mean±SD) found for the Dose-WL tests (LR: 0.5±0.4mm; AP: 0.5±0.4mm; SI: 0.6±0.2mm) were in most cases less than 1mm, and they were significantly smaller (all p<0.05) than the maximum deviations reported by the Pointer-WL tests (LR: 1.3±0.3mm; AP: 1.2±0.4mm; SI: 1.1±0.3mm).
The Dose-WL test described in this study allows estimating the spatial accuracy of the prescription isodose line.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Diffraction patterns of polyacrylic acid (PAA) encapsulated-(Fe)-modified ZnAl hydrotalcite (ZnAlH) showed the integration of Fe in the H lattice, resulting in a hybrid nanocomposite (Fe-PAA-ZnAlH), ...which was mainly verified with the characteristic shift in the 59–63° (2θ) region of the ZnAlH (110) reflection plane. The rise in the unit cell parameters (c and a) as the Fe % incremented, denoted incorporation of Fe in the ZnAlH red. Nonetheless, changes in the immobilizer molecular weight (PAA MW) from 1250 kDa to 5.1 kDa did not cause a difference in the distance between layers (c parameter) but in the cation-cation separation (a parameter), which meant that the nanoparticle was not located between layers, but in the lattice. The resulting band gap energies of the calcined hybrid nanocomposites were among 1.07–1.21 eV, which is an additional support of Fe+3 integration, suggesting insertion of Fe+3 3d orbitals between the valence and the conduction band of ZnO. Furthermore, nZVI were prepared through a pre-agglomeration reduction method, where COOH-groups were bound to metal cations. Initially, aqueous Fe+2 was bound to PAA Fe+2-PAA, then reduced to obtain enclosed hybrid (nZVI-PAA). Less stability and more aggregation were observed with the lower molecular weight PAA. Additionally, PAA dissociation caused by pH changes affected the clustering of the nZVI particles. At higher MW, the hydrodynamic diameter and size distribution become smaller and tighter, respectively, allowing a more monodispersed population with sphere shape and organized in core–shell beads chains.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The induction of antibodies specific for the influenza HA protein stalk domain is being pursued as a universal strategy against influenza virus infections. However, little work has been done looking ...at natural or induced antigenic variability in this domain and the effects on viral fitness. We analyzed human H1 HA head and stalk domain sequences and found substantial variability in both, although variability was highest in the head region. Furthermore, using human immune sera from pandemic A/California/04/2009 immune subjects and mAbs specific for the stalk domain, viruses were selected in vitro containing mutations in both domains that partially contributed to immune evasion. Recombinant viruses encoding amino acid changes in the HA stalk domain replicated well in vitro, and viruses incorporating two of the stalk mutations retained pathogenicity in vivo. These findings demonstrate that the HA protein stalk domain can undergo limited drift under immune pressure and the viruses can retain fitness and virulence in vivo, findings which are important to consider in the context of vaccination targeting this domain.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Information on tuberculosis (TB) and coronavirus disease 2019 (COVID-19) is still limited. The aim of this study was to describe the features of the TB/COVID-19 co-infected individuals from a ...prospective, anonymised, multicountry register-based cohort with special focus on the determinants of mortality and other outcomes.
We enrolled all patients of any age with either active TB or previous TB and COVID-19. 172 centres from 34 countries provided individual data on 767 TB-COVID-19 co-infected patients, (>50% population-based).
Of 767 patients, 553 (74.0%) out of 747 had TB before COVID-19 (including 234 out of 747 with previous TB), 71 (9.5%) out of 747 had COVID-19 first and 123 (16.5%) out of 747 had both diseases diagnosed within the same week (n=35 (4.6%) on the same day). 85 (11.08%) out of 767 patients died (41 (14.2%) out of 289 in Europe and 44 (9.2%) out of 478 outside Europe; p=0.03): 42 (49.4%) from COVID-19, 31 (36.5%) from COVID-19 and TB, one (1.2%) from TB and 11 from other causes. In the univariate analysis on mortality the following variables reached statistical significance: age, male gender, having more than one comorbidity, diabetes mellitus, cardiovascular disease, chronic respiratory disease, chronic renal disease, presence of key symptoms, invasive ventilation and hospitalisation due to COVID-19. The final multivariable logistic regression model included age, male gender and invasive ventilation as independent contributors to mortality.
The data suggest that TB and COVID-19 are a "cursed duet" and need immediate attention. TB should be considered a risk factor for severe COVID disease and patients with TB should be prioritised for COVID-19 preventative efforts, including vaccination.
Small noncoding RNAs (sRNAs) are usually expressed in the cell to face a variety of stresses. In this report we disclose the first target for SraL (also known as RyjA), a sRNA present in many ...bacteria, which is highly induced in stationary phase. We also demonstrate that this sRNA is directly transcribed by the major stress σ factor σ(S) (RpoS) in Salmonella enterica serovar Typhimurium. We show that SraL sRNA down-regulates the expression of the chaperone Trigger Factor (TF), encoded by the tig gene. TF is one of the three major chaperones that cooperate in the folding of the newly synthesized cytosolic proteins and is the only ribosome-associated chaperone known in bacteria. By use of bioinformatic tools and mutagenesis experiments, SraL was shown to directly interact with the 5' UTR of the tig mRNA a few nucleotides upstream of the Shine-Dalgarno region. Namely, point mutations in the sRNA (SraL*) abolished the repression of tig mRNA and could only down-regulate a tig transcript target with the respective compensatory mutations. We have also validated in vitro that SraL forms a stable duplex with the tig mRNA. This work constitutes the first report of a small RNA affecting protein folding. Taking into account that both SraL and TF are very well conserved in enterobacteria, this work will have important repercussions in the field.
Newly synthesized carbosilane copper dendrimers (CCD) with chloride and nitrate surface groups seem to be good candidates to be used as gene and drug carriers in anti-cancer therapy, due to their ...properties such as size and surface charge. Copper attached to the nanoparticles is an important element of many biological processes and recently their anti-cancer properties have been widely examined. Zeta size and potential, transmission electron microscopy (TEM), circular dichroism (CD), analysis of haemolytic activity, and fluorescence anisotropy techniques were used to characterize copper dendrimers. Additionally, their cytotoxic properties toward normal (PBMC) and cancer (1301; HL-60) cells were examined. All tested dendrimers were more cytotoxic against cancer cells in comparison with normal cells.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Angiogenesis is a requirement for the sustained growth and proliferation of solid tumors, and the development of new compounds that induce a sustained inhibition of the proangiogenic signaling ...generated by tumor hypoxia still remains as an important unmet need. In this work, we describe a new antiangiogenic compound (22) that inhibits proangiogenic signaling under hypoxic conditions in breast cancer cells. Compound 22 blocks the MAPK pathway, impairs cellular migration under hypoxic conditions, and regulates a set of genes related to angiogenesis. These responses are mediated by HIF-1α, since the effects of compound 22 mostly disappear when its expression is knocked-down. Furthermore, administration of compound 22 in a xenograft model of breast cancer produced tumor growth reductions ranging from 46 to 55% in 38% of the treated animals without causing any toxic side effects. Importantly, in the responding tumors, a significant reduction in the number of blood vessels was observed, further supporting the mechanism of action of the compound. These findings provide a rationale for the development of new antiangiogenic compounds that could eventually lead to new drugs suitable for the treatment of some types of tumors either alone or in combination with other agents.
Inborn errors of immunity may present with autoimmunity and autoinflammation as hallmark clinical manifestations. We aimed to identify the potential monogenic causes of autoimmune disorders in 26 ...patients from a pediatric reference hospital in Mexico through whole-exome sequencing. We specifically selected patients with a family history of autoimmune diseases, early-onset symptoms, and difficult-to-control autoimmune disorders or autoimmunity associated with infection predisposition. We identified the genetic variants that were compatible with the patients' phenotype in 54% of the patients. Autoimmune diseases are often caused by a combination of genetic factors, but cases that appear at a young age are resistant to treatment or occur in clusters, as well as the presence of autoimmune symptoms alongside infectious diseases should raise suspicion for an underlying inborn error of immunity.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This study aimed to describe the feasibility of the online adaptive radiation therapy (oART) method developed at the Hospital Quirónsalud Barcelona for prostate cancer, using a standard C-arm linear ...accelerator (linac) and without the support of artificial intelligence.
The first 18 patients treated at the Hospital Quirónsalud Barcelona with the developed oART method were included. An ultrahypofractionated radiation therapy scheme consisting of 7 × 6.1 Gy was used. Patients were treated on 2 conventional Varian C-arm linacs. For each patient, a reference plan based on a planning computed tomography (pCT) scan was generated using the Eclipse system. On each treatment session, the pCT scan was rigidly registered with the daily cone beam computed tomography (CT) scan. The pCT-based target (prostate) and organs at risk were mapped onto the cone beam CT images and manually adapted to take into account the anatomy of the day. The reference plan was then copied to the cone beam CT scan, and a full reoptimization was done for the current anatomy (adapted plan). For each treatment session, the unaltered reference plan was recomputed on the daily cone beam CT scan by mimicking the soft-tissue alignment performed per our standard procedure (nonadapted plan). Over the 126 adapted sessions from the 18 patients, a dosimetric comparison of adapted against nonadapted plans was done.
A significant difference in the target coverage was found between the adapted and nonadapted plans (97.1 vs 90.4; P < .001) in favor of adapting. Without online adaptation, the optimal coverage of the prostate was not attained in 35% of fractions. Adapting allows for the improvement of the target coverage with compliance of all organ-at-risk dose constraints in all treatment fractions.
The oART technique described in this study is technically feasible with a C-arm linac. To our knowledge, this is the first clinical experience with oART for prostate cancer including full replanning and delivered with a C-arm linac without artificial intelligence capability.
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