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As demonstrated by us earlier and by other researchers, a diet containing freeze-dried black raspberries (BRB) inhibits DNA damage and carcinogenesis in animal models. We tested the hypothesis that the inhibition of DNA damage by BRB is due, in part, to the enhancement of DNA repair capacity evaluated in the human HeLa cell extract system, an established in vitro system for the assessment of cellular DNA repair activity. The pre-treatment of intact HeLa cells with BRB extracts (BRBE) enhances the nucleotide excision repair (NER) of a bulky deoxyguanosine adduct derived from the polycyclic aromatic carcinogen benzo[a]pyrene (BP-dG) by ~24%. The NER activity of an oxidatively-derived non-bulky DNA lesion, guanidinohydantoin (Gh), is also enhanced by ~24%, while its base excision repair activity is enhanced by only ~6%. Western Blot experiments indicate that the expression of selected, NER factors is also increased by BRBE treatment by ~73% (XPA), ~55% (XPB), while its effects on XPD was modest (<14%). These results demonstrate that BRBE significantly enhances the NER yields of a bulky and a non-bulky DNA lesion, and that this effect is correlated with an enhancement of expression of the critically important NER factor XPA and the helicase XPB, but not the helicase XPD.

The SARS-CoV-2 helicase, non-structural protein 13 (Nsp13), plays an essential role in viral replication, translocating in the 5′ → 3′ direction as it unwinds double-stranded RNA/DNA. We investigated the impact of structurally distinct DNA lesions on DNA unwinding catalyzed by Nsp13. The selected lesions include two benzo[a]pyrene (B[a]P)-derived dG adducts, the UV-induced cyclobutane pyrimidine dimer (CPD), and the pyrimidine (6–4) pyrimidone (6–4PP) photolesion. The experimentally observed unwinding rate constants (kobs) and processivities (P) were examined. Relative to undamaged DNA, the kobs values were diminished by factors of up to ~15 for B[a]P adducts but only by factors of ~2–5 for photolesions. A minor-groove-oriented B[a]P adduct showed the smallest impact on P, which decreased by ~11% compared to unmodified DNA, while an intercalated one reduced P by ~67%. However, the photolesions showed a greater impact on the processivities; notably, the CPD, with the highest kobs value, exhibited the lowest P, which was reduced by ~90%. Our findings thus show that DNA unwinding efficiencies are lesion-dependent and most strongly inhibited by the CPD, leading to the conclusion that processivity is a better measure of DNA lesions’ inhibitory effects than unwinding rate constants.

DNA helicase unwinding activity can be inhibited by small molecules and by covalently bound DNA lesions. Little is known about the relationships between the structural features of DNA lesions and their impact on unwinding rates and processivities. Employing E.coli RecQ helicase as a model system, and various conformationally defined DNA lesions, the unwinding rate constants kobs = kU + kD, and processivities P = (kU/(kU + kD) were determined (kU, unwinding rate constant; kD, helicase-DNA dissociation rate constant). The highest kobs values were observed in the case of intercalated benzo[a]pyrene (BP)-derived adenine adducts, while kobs values of guanine adducts with minor groove or base-displaced intercalated adduct conformations were ~10–20 times smaller. Full unwinding was observed in each case with the processivity P = 1.0 (100% unwinding). The kobs values of the non-bulky lesions T(6−4)T, CPD cyclobutane thymine dimers, and a guanine oxidation product, spiroiminodihydantoin (Sp), are up to 20 times greater than some of the bulky adduct values; their unwinding efficiencies are strongly inhibited with processivities P = 0.11 (CPD), 0.062 (T(6−4)T), and 0.63 (Sp). These latter observations can be accounted for by correlated decreases in unwinding rate constants and enhancements in the helicase DNA complex dissociation rate constants.

The SARS 2 (Covid 19) helicase nsp13 plays a critically important role in the replication of the Corona virus by unwinding double-stranded RNA (and DNA) with a 5 prime to 3 prime strand polarity. Here we explored the impact of single, structurally defined covalent DNA lesions on the helicase activity of nsp13 in aqueous solutions, The objectives were to derive mechanistic insights into the relationships between the structures of DNA lesions, the DNA distortions that they engender, and the inhibition of helicase activity. The lesions included two bulky stereoisomeric N2-guanine adducts derived from the reactions of benzo[a]pyrene diol epoxide with DNA. The trans-adduct assumes a minor groove conformation, while the cis-product adopts a base-displaced intercalated conformation. The non-bulky DNA lesions included the intra-strand cross-linked thymine dimers, the cis-syn-cyclobutane pyrimidine dimer, and the pyrimidine (6–4) pyrimidone photoproduct. All four lesions strongly inhibit the helicase activity of nsp13, The UV photolesions feature a 2 - 5-fold smaller inhibition of the nsp13 unwinding activity than the bulky DNA adducts, and the kinetics of these two pairs of DNA lesions are also different. The connections between the structural features of these four DNA lesions and their impact on nsp13 unwinding efficiencies are discussed. Competing Interest Statement The authors have declared no competing interest.

Essential oils (EOs) of three native species Baccharis uncinella, B. retusa and B. calvescens, obtained through hydrodistillation, were analyzed by GC-MS and GC-FID for seasonality, and the antimicrobial and anti-proliferative activities were evaluated. EO of B. calvescens and B. uncinella consisted mainly of oxygenated sesquiterpenes, while in the EO of B. retusa, monoterpene hydrocarbons were predominant. The highest antimicrobial activity was observed for spring B. uncinella EO against S. aureus, C. albicans and summer B. uncinella EO against C. albicans and B. subtilis. Essential oils of B. calvescens showed more effective anti-proliferative activity than B. retusa EO and B. uncinella EO. This is the first study of the EO of B. retusa, and it was demonstrated that the majority composition was different in all seasons of the year, justifying the importance of the seasonal study. Furthermore, the summer and spring EO showed potent cytostatic effects against the K562 and OVCAR-03 cell lines, respectively. For each species, PCA differentiated the EO chemical composition seasonally. PCA of all samples distinguished the three species. This study underscores the importance of assessing seasonal variation in the chemical composition and biological activities of essential oils, highlighting the potential of compounds spathulenol, caryophyllene oxide, limonene and α-pinene for achieving the desired product properties.

The present study aimed to investigate the influence of ripening on the physicochemical, microbiological aspects, and fatty acid profile of Artisanal Coalho Cheeses and to detect if there are peptides with bioactive potential in their composition. Artisanal Coalho Cheese samples were kindly provided by a dairy farm located in Brazil in the Rio Grande do Norte state. A completely randomized design was adopted, with four maturation periods (0, 30, 45, and 60 days). Physicochemical traits (pH, total solids, moisture, non-fat solids, fat in total solids, protein, ash, fatty acid profile) and microbiological characterization ( Salmonella sp, Listeria monocytogenes , total and thermotolerant coliforms, Staphylococcus aureus ) were analyzed on cheese samples. Additionally, assays were performed for antioxidant and antihypertensive bioactivity through ACE and antimicrobial inhibition of the peptides extracted from the samples. There was a linear increase in total solids and ash content and a decrease in moisture content with increasing maturation time. The matured cheese samples had a lower pH than fresh Artisanal Coalho Cheese. Twenty-seven fatty acids were identified in the cheeses: 15 saturated, 07 monounsaturated, and 05 polyunsaturated, with a linear reduction of essential fatty acids (n6 and n3) during maturation. The microbiological quality of the cheeses was satisfactory, with an absence of undesirable bacteria in 92% of the cheese samples. Water-soluble peptide fractions from all periods tested showed antioxidant and antihypertensive potential with ACE control, and the maturation process potentiated these capacities, with a decline in these activities observed at 60 days. The antimicrobial activity against Gram-positive and Gram-negative bacteria increased with maturation, reaching better results until 60 days. The maturation process on wooden planks in the periods of 30, 45, and 60 days allows the production of Artisanal Coalho Cheese of an innovative character, safe to consumers from the microbiological point of view, with differentiated physicochemical and functional characteristics and good quality of lipid fraction compared to fresh cheese, enabling the addition of value to the dairy chain.

Since the COVID-19 pandemic emerged, vaccination has been the core strategy to mitigate the spread of SARS-CoV-2 in humans. This paper analyzes the impact of COVID-19 vaccination on hospitalizations and deaths in the state of Rio Grande do Norte, Brazil. We analyzed data from 23,516 hospitalized COVID-19 patients diagnosed between April 2020 and August 2021. We excluded the data from patients hospitalized through direct occupancy, unknown outcomes, and unconfirmed COVID-19 cases, resulting in data from 12,635 patients cross-referenced with the immunization status during hospitalization. Our results indicated that administering at least one dose of the immunizers was sufficient to significantly reduce the occurrence of moderate and severe COVID-19 cases among patients under 59 years. Considering the partially or fully immunized patients, the mean age is similar between the analyzed groups, despite the occurrence of comorbidities and higher than that observed among not immunized patients. Thus, immunized patients present lower Unified Score for Prioritization (USP) levels when diagnosed with COVID-19. Our data suggest that COVID-19 vaccination significantly reduced the hospitalization and death of elderly patients (60+ years) after administration of at least one dose. Comorbidities do not change the mean age of moderate/severe COVID-19 cases and the days required for the hospitalization of these patients.

Endothelial cells are thought to play a central role in the pathogenesis of antiphospholipid syndrome (APS). Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been shown to improve endothelial function in a number of diseases; thus, it could be of high clinical relevance in APS. The aim of this study was to evaluate the efficacy of n-3 PUFA supplementation on endothelial function (primary outcome) of patients with primary APS (PAPS). A 16-week randomized clinical trial was conducted with 22 adult women with PAPS. Patients were randomly assigned (1:1) to receive placebo (PL,  = 11) or n-3 PUFA (ω-3,  = 11) supplementation. Before (pre) and after (post) 16 weeks of the intervention, patients were assessed for endothelial function (peripheral artery tonometry) (primary outcome). Patients were also assessed for systemic markers of endothelial cell activation, inflammatory markers, dietary intake, international normalized ratio (INR), and adverse effects. At post, ω-3 group presented significant increases in endothelial function estimates reactive hyperemia index (RHI) and logarithmic transformation of RHI (LnRHI) when compared with PL (+13 vs. -12%,  = 0.06, ES = 0.9; and +23 vs. -22%,  = 0.02, ES = 1.0). No changes were observed for e-selectin, vascular adhesion molecule-1, and fibrinogen levels (  > 0.05). In addition, ω-3 group showed decreased circulating levels of interleukin-10 (-4 vs. +45%,  = 0.04, ES = -0.9) and tumor necrosis factor (-13 vs. +0.3%,  = 0.04, ES = -0.95) and a tendency toward a lower intercellular adhesion molecule-1 response (+3 vs. +48%,  = 0.1, ES = -0.7) at post when compared with PL. No changes in dietary intake, INR, or self-reported adverse effects were observed. In conclusion, 16 weeks of n-3 PUFA supplementation improved endothelial function in patients with well-controlled PAPS. These results support a role of n-3 PUFA supplementation as an adjuvant therapy in APS. Registered at http://ClinicalTrials.gov as NCT01956188.

Studies demonstrate that there is a lack of effective ergonomic principles for adopting a neutral posture during the execution of dental procedures. ISO 11.226:2000 Standard, Corr. 1:2006 has been thoroughly evaluated and adapted to the way that dentists work by the European Society of Dental Ergonomics (ESDE). However, after 15 years, no studies that showed strong evidence of effectiveness in reducing the prevalence of awkward posture in applying its parameters within the scope of dental practice were found. The aim of this study was to verify the effectiveness of applying the ergonomic parameters proposed by the European Society of Dental Ergonomics (ESDE) and ISO 11226 in reducing the prevalence of the main awkward postures adopted by female dental surgeons during the execution of dental scaling on a dental mannequin. A randomized clinical trial was carried out with sixty dental surgeons randomly assigned to two groups: the intervention group, who received instructions and theoretical and practical ergonomic training; and the control group, who received the same training only at the end of the study. For data analysis, Software IBM SPSS 27 and RStudio was used. Descriptive statistics were performed to verify the effectiveness of the intervention, and generalized linear models (specifically, generalized estimated equation models) were used. Poisson distribution was carried out with log link function and network analyses. Sixty female dental surgeons participated in the study. Twenty-two were distributed in the intervention group and thirty-eight in the control group. It was found that ergonomic training enabled a 63% reduction in the prevalence of awkward postures and that there was a statistically significant difference (p < 0.001) only in the intervention group. The analyses showed that the estimated marginal means of postures not recommended in the groups’ initial control, final control, initial intervention, and final intervention were 8.6, 8.2, 9.0, and 3.4, respectively. The relationship of networks analyses of the variables is shown with different profiles in the control and intervention groups, but the same pattern between the groups only vary in the strength and direction of the correlations. It was concluded that the ergonomic training based on the parameters of ISO 11226 and DIN EN 1005-4, and its adaptations to the dental practice provided by the European Society of Dental Ergonomics, as well as recent studies, contributed significantly to reducing the prevalence of awkward postures adopted by female dentists during the simulation of the basic periodontal procedures; however, it was not effective enough to improve the posture of the head and neck.

This study sought to investigate which temporomandibular disorders (TMD) can be expected in patients with ankylosing spondylitis (AS) and to determine the combined impact of these conditions on the psychological status, chronic pain, and functional disability. A cross-sectional study composed of 30 patients between 18 and 65 years with ankylosing spondylitis was performed. The research protocol considered the evaluation of outcomes related to the ankylosing spondylitis (HLA-B27 antigen, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Health Assessment Questionnaire - Spondylitis (HAQ-S)) and temporomandibular disorders (axis I and II of the Research Diagnostic Criteria for Temporomandibular Disorders - RDC/TMD). Descriptive analyses were applied to express the results. The sample presented both AS and TMD, most of them (24) were diagnosed with conventional AS (HLA-B27 positive). The BASDAI was scored as 7.70 (2.30) (high activity of AS disease). Functional disability represented by high scores of BASFI [7.00 (2.63)] and HAQ-S [1.79 (0.62)] demonstrates the severe impact of the disease on the daily routine and quality of life. According to RDC/TMD diagnostic criteria, 17 (57%) share the three groups of TMD, and 9 (30%) share two groups of TMD (Group I and III). Over 73% of the volunteers scored high levels of chronic pain (Grade III and IV) associated with a high depression scale score. The sample scored the somatization scale (with and without pain) as severe. Patients with ankylosing spondylitis presented a high prevalence of temporomandibular disorder, most of them having the degenerative forms of TMJ disease. AS and TMD cause moderate to severe chronic pain and a negative impact on psychological status and functional capacities.