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Fructooligosaccharides (FOS) are fructose oligomers beneficial to human health and nutrition for prebiotic sugars. Their production occurs by a transfructosylation reaction in sucrose molecules catalyzed by fructosyltransferase enzymes (FTase, E.C.2.4.1.9) adhered to microbial cells. The purpose of this work was to study the preparation, enzymatic activity, and stability of glutaraldehyde-crosslinked Aspergillus oryzae IPT-301 cells used as a biocatalyst for the transfructosylation reaction of sucrose in a packed bed reactor (PBR), aiming at FOS production. The highest transfructosylation activity (AT) was presented by the biocatalyst prepared by cross-linking at 200 rpm and 45 min. The highest AT in the PBR was obtained at 50 °C, with flow rates from 3 mL min-1 to 5 mL min-1 and sucrose concentrations of 473 g L-1 and 500 g L-1. The enzymatic kinetics was described using the Michaelis-Menten model. Finally, the biocatalyst showed constant AT of approximately 75 U g-1 and 300 U g-1 for 12 h of reaction in the PBR operating in continuous and discontinuous flow, respectively. These results demonstrate a high potential of glutaraldehyde-crosslinked A. oryzae IPT-301 cells as heterogeneous biocatalysts for the continuous production of FOS in PBR reactors.

Abstract Background Dengue is the most important mosquito-borne viral disease worldwide. Dengue virus comprises four antigenically related viruses named dengue virus type 1 to 4 (DENV1-4). DENV-3 was re-introduced into the Americas in 1994 causing outbreaks in Nicaragua and Panama. DENV-3 was introduced in Brazil in 2000 and then spread to most of the Brazilian States, reaching the neighboring country, Paraguay in 2002. In this study, we have analyzed the phylogenetic relationship of DENV-3 isolated in Brazil and Paraguay with viruses isolated worldwide. We have also analyzed the evolutionary divergence dynamics of DENV-3 viruses. Results The entire open reading frame (ORF) of thirteen DENV-3 isolated in Brazil (n = 9) and Paraguay (n = 4) were sequenced for phylogenetic analysis. DENV-3 grouped into three main genotypes (I, II and III). Several internal clades were found within each genotype that we called lineage and sub-lineage. Viruses included in this study belong to genotype III and grouped together with viruses isolated in the Americas within the lineage III. The Brazilian viruses were further segregated into two different sub-lineage, A and B, and the Paraguayan into the sub-lineage B. All three genotypes showed internal grouping. The nucleotide divergence was in average 6.7% for genotypes, 2.7% for lineages and 1.5% for sub-lineages. Phylogenetic trees constructed with any of the protein gene sequences showed the same segregation of the DENV-3 in three genotypes. Conclusion Our results showed that two groups of DENV-3 genotypes III circulated in Brazil during 2002–2009, suggesting different events of introduction of the virus through different regions of the country. In Paraguay, only one group DENV-3 genotype III is circulating that is very closely related to the Brazilian viruses of sub-lineage B. Different degree of grouping can be observed for DENV-3 and each group showed a characteristic evolutionary divergence. Finally, we have observed that any protein gene sequence can be used to identify the virus genotype.

Abstract Background Organophosphates and pyrethroids are used widely in Brazil to control Aedes aegypti, the main vector of dengue viruses, under the auspices of the National Programme for Dengue Control. Resistance to these insecticides is widespread throughout Brazil. In Ceará the vector is present in 98% of districts and resistance to temephos has been reported previously. Here we measure resistance to temephos and the pyrethroid cypermethrin in three populations from Ceará and use biochemical and molecular assays to characterise resistance mechanisms. Results Resistance to temephos varied widely across the three studied populations, with resistance ratios (RR95) of 7.2, 30 and 192.7 in Juazeiro do Norte, Barbalha and Crato respectively. The high levels of resistance detected in Barbalha and Crato (RR95 ≥ 30) imply a reduction of temephos efficacy, and indeed in simulated field tests reduced effectiveness was observed for the Barbalha population. Two populations (Crato and Barbalha) were also resistant to cypermethrin, whilst Juazeiro do Norte showed only an altered susceptibility. The Ile1011Met kdr mutation was detected in all three populations and Val1016Ile in Crato and Juazeiro do Norte. 1011Met was significantly associated with resistance to cypermethrin in the Crato population. Biochemical tests showed that only the activity of esterases and GSTs, among the tested detoxification enzymes, was altered in these populations when compared with the Rockefeller strain. Conclusions Our results demonstrate that two A. aegypti populations from Ceará are under strong selection pressure by temephos, compromising the field effectiveness of this organophosphate. Our results also provide evidence that the process of reducing resistance to this larvicide in the field is difficult and slow and may require more than seven years for reversal. In addition, we show resistance to cypermethrin in two of the three populations studied, and for the first time the presence of the allele 1016Ile in mosquito populations from northeastern Brazil. A significant association between 1011Met and resistance was observed in one of the populations. Target-site mechanisms seem not to be implicated in temephos resistance, reinforcing the idea that for the studied populations, detoxification enzymes most likely play a major role in the resistance to this insecticide.

Abstract Background Aromatase, the cytochrome P-450 enzyme (CYP19) responsible for estrogen biosynthesis, is an important target for the treatment of estrogen-dependent breast cancer. In fact, the use of synthetic aromatase inhibitors (AI), which induce suppression of estrogen synthesis, has shown to be an effective alternative to the classical tamoxifen for the treatment of postmenopausal patients with ER-positive breast cancer. New AIs obtained, in our laboratory, by modification of the A and D-rings of the natural substrate of aromatase, compounds 3a and 4a, showed previously to efficiently suppress aromatase activity in placental microsomes. In the present study we have investigated the effects of these compounds on cell proliferation, cell cycle progression and induction of cell death using the estrogen-dependent human breast cancer cell line stably transfected with the aromatase gene, MCF-7 aro cells. Results The new steroids inhibit hormone-dependent proliferation of MCF-7aro cells in a time and dose-dependent manner, causing cell cycle arrest in G0/G1 phase and inducing cell death with features of apoptosis and autophagic cell death. Conclusion Our in vitro studies showed that the two steroidal AIs, 3a and 4a, are potent inhibitors of breast cancer cell proliferation. Moreover, it was also shown that the antiproliferative effects of these two steroids on MCF-7aro cells are mediated by disrupting cell cycle progression, through cell cycle arrest in G0/G1 phase and induction of cell death, being the dominant mechanism autophagic cell death. Our results are important for the elucidation of the cellular effects of steroidal AIs on breast cancer.

Objective: The aim of this study was to investigate changes in dietary intake, anthropometric parameters and markers of oxidative stress in 40 women who underwent surgery, chemotherapy or radiation therapy for breast cancer.Methods: Pretreatment and post-treatment measurements included data collected through a food frequency questionnaire, weight and height to calculate the body mass index (BMI) and oxidative stress markers assessed from blood reduced glutathione (GSH), serum antioxidant capacity (AC), plasma thiobarbituric acid reactive substances (TBARS), serum lipid hydroperoxides (LH) and plasma carbonyls. Differences were compared using paired Student's t-test or paired Wilcoxon's test.Results: A significant increase (P < 0.05) in the intake of the food groups: meat and eggs, dairy products, beans, oils and fats, as well as food from the subgroups: red meat, milk and other dairy products rich in fat, fruit rich in vitamin C and vegetable fats was found after treatments. There was a significant increase in body weight (P < 0.05), BMI (P < 0.05), levels of TBARS (P < 0.0001), LH (P < 0.005) and carbonyls (P < 0.0001) and a significant decrease of levels of AC (P < 0.005) and GSH (P < 0.0001).Conclusion: Breast cancer diagnosis and treatments were associated with dietary intake changes and increased body weight, BMI and oxidative stress. These potential changes have important implications for preventive nutrition counseling. [ABSTRACT FROM AUTHOR]

Actinic cheilitis (AC) is a lip disorder, with no standard treatment. Imiquimod (IMIQ) is an immunomodulator that treat precancerous lesions; however, its commercial form causes severe adverse effects. This study aimed to assess IMQ release from a chitosan hydrogel containing 0.05 % nanoencapsulated (NANO) imiquimod (IMIQ-0.05 %-NANO) and its efficacy in AC treatment. The hydrogels were prepared by incorporating chitosan into polymeric nanocapsules (NCimiq) loaded with IMQ, produced using the interfacial deposition of preformed polymer method. IMQ release was evaluated using automated Franz Cells. A triple-blind randomized controlled trial (49 subjects) compared the efficacy of: IMIQ-0.05 %-NANO, 5 % free imiquimod (IMIQ-5 %), 0.05 % free imiquimod (IMIQ-0.05 %), and placebo hydrogel. The IMIQ-NANO-0.05 % and IMIQ-5 % groups exhibited significantly higher rates of clinical improvement (p < 0.05); however, the IMIQ-5 % group experienced more adverse effects (92.3 % of subjects) compared to other groups (p < 0.05). In conclusion, in the studied sample, IMIQ-NANO-0.05 % was a safe and effective option to treat AC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cancer resistance to drugs and chemotherapy is a problem faced by public health systems worldwide. Repositioning antimicrobial peptides could be an efficient strategy to overcome that problem. This study aimed at repurposing antimicrobial peptides PepGAT and PepKAA for cancer treatment. After screening against several cancers, PepGAT and PepKAA presented IC50 values of 125.42 and 40.51 μM at 72 h toward colorectal cancer (CRC) cells. The mechanisms of action revealed that both peptides induced cell cycle arrest in G2/M and drove HCT-116 cells to death by triggering apoptosis. qPCR analysis revealed that peptides modulated gene expression in apoptosis, corroborating the data from caspase 3/7 and flow cytometry experiments. Yet, peptides induced ROS overaccumulation and increased membrane permeabilization, pore formation, and loss of internal content, leading to death. Additionally, peptides were able to inhibit cell invasion. Previous studies from the same group attested to no toxicity to normal human cells. Thus, PepGAT and PepKAA have great potential as anticancer molecules., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

In Brazil, around 80% of snakebites are caused by snakes of the genus Bothrops. A three-dimensional culture model was standardized and used to perform treatments with Bothrops erythromelas venom (BeV) and its antivenom (AV). The MRC-5 and L929 cell lines were cultured at increasing cell densities. Morphometric parameters were evaluated through images obtained from an inverted microscope: solidity, circularity, and Feret diameter. L929 microtissues (MT) showed better morphometric data, and thus they were used for further analysis. MT viability was assessed using the acridine orange and ethidium bromide staining method, which showed viable cells in the MT on days 5, 7, and 10 of cultivation. Histochemical and histological analyses were performed, including hematoxylin/eosin staining, which showed a good structure of the spheroids. Alcian blue staining revealed the presence of acid proteoglycans. Immunohistochemical analysis with ki-67 showed different patterns of cell proliferation. The MT were also subjected to pharmacological tests using the BeV, in the presence or absence of its AV. The results showed that the venom was not cytotoxic, but it caused morphological changes. The MT showed cell detachment, losing their structure. The antivenom was able to partially prevent the venom activities., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Periodontitis is clinically characterized by destruction of the tooth support system and tooth loss. Porphyromonas gingivalis (Pg) plays a dominant role in periodontitis. Fractions and isolated compounds from an acetone-water extract of the roots of Limonium brasiliense (Lb) were tested in vitro for their anti-adhesive capacity against Pg on human KB buccal cells, influence on gingipains, the main virulence factors of Pg, and biofilm formation. Fractions EAF and FLB7 (50 μg/mL) reduced the bacterial adhesion of Pg to KB cells significantly (63 resp. 70%). The proanthocyanidin samarangenin A inhibited the adhesion (72%, 30 μM), samarangenin B (71%, 20 μM), and the flavan-3-ol epigallocatechin-3-O-gallate (79%, 30 μM). Fraction AQF, representing hydrophilic compounds, reduced the proteolytic activity of Arginin-specific gingipain (IC 50 12.78 μg/mL). Fractions EAF and FLB7, characterized by lipohilic constituents, inhibited Arg-gingipain (IC 50 3 μg/mL). On Lysine-specific gingipain, AQF has an IC 50 15.89, EAF 14.15, and FLB7 6 μg/mL. The reduced bacterial adhesion is due to a strong interaction of proanthocyanidins with gingipains. AQF, EAF, and FLB7 significantly inhibited biofilm formation: IC 50 11.34 (AQF), 11.66 (EAF), and 12.09 μg/mL (FLB7). In silico analysis indicated, that the polyphenols act against specific targets of Pg, not affecting mammalian cells. Therefore, Lb might be effective for prevention of periodontal disease by influencing virulence factors of Pg., Competing Interests: Declaration of competing interest This study was financially supported by CNPq, for providing a student grant to Raquel Isolani for the program “Science Without Borders” – CNPq (Grant #200173/2018–9). Residual expenses were borne by intramural annual budgets from the University of Münster to Andreas Hensel, the State University of Maringá to and project's funding agencies, CAPES, FINEP, CNPq to João Carlos Palazzo de Mello (Grant #401490/2014-9). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Melanoma is a type of tumor skin with high metastatic potential. Reconstructed human skin, development for pre-clinic assay, are make using primary human cells, but with same limitations. The aim this study was to characterize a cell culture model, with structure similar to human skin containing melanoma cells entirely from cell lines. Reconstructed skin with melanoma were development using human fibroblasts (MRC5), human epidermal keratinocytes (HaCat), and human melanoma (SK-MEL-28) embedded in collagen type I. The structure was characterized by hematoxylin-eosin stained, as well as points of melanoma cell invasion, which was associated with activity of MMPs (MMP-2 and MMP-9) by zymographic method. Then, the gene expression of the target molecular mechanisms involved in melanoma progression were evaluated. Here, the model development showed a region epidermis organized and separated from the dermis, with fibroblast cells confined and melanoma cells form delimited area invasion. MMP-2 and MMP-9 were identified during of cell culture and gene expression of BRAF, NRAS, and Vimentin was confirmed. The proposed model provides one more opportunity to study in vitro tumor biology of melanoma and also to allows the study of new drugs with more reliable results then whats we would find in vivo., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marne Carvalho de Vasconcellos has patent #BR 102019 017285 1 pending to Licensse. If there are other authors, they 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 © 2023. Published by Elsevier Ltd.)

To examine the effects of 7-days juçara powder (JP) intake on oxidative stress biomarkers and endurance and sprint cycling performances. In a randomized, placebo-controlled, crossover, and triple-blind study, 20 male trained cyclists were assigned to intake 10 g of JP (240 mg anthocyanins) or placebo (PLA) for 7 days and performed a cycling time-to-exhaustion (TTE). A 5 s cycling sprint was performed before and after the cycling TTE. Blood oxidative stress biomarkers and lactate concentration where evaluated 1 h before (T-1), immediately after (T0), and 1 h after (T1) the cycling TTE. The mean duration time for the cycling TTE was 8.4 ± 6.0% (63 ± 17 s) longer in the JP condition (JP: 751 ± 283 s) compared to PLA (688 ± 266 s) ( P  < 0.019). Two-way repeated measures Analysis of variance showed an increase in the JP condition for reduced glutathione (GSH) ( P  = 0.049) at T0 ( P  = 0.039) and T1 ( P  = 0.029) compared to PLA with a moderate effect size at T0 ( d  = 0.61) and T1 ( d  = 0.57). Blood lactate levels increased over time in both conditions ( P ≤  0.001). No differences were observed for the post-TTE sprint fatigue index, total phenols, protein carbonyls, and glutathione peroxidase activity. Seven-day intake of JP improved cycling endurance performance and increased GSH levels but had no effect on lactate and cycling sprint-induced fatigue., Competing Interests: The authors declare that they have no competing interests.

Gastric adenocarcinoma is a complex disease with diverse genetic modifications, including Anaplastic Lymphoma Kinase (ALK) gene changes. The ALK gene is located on chromosome 2p23 and encodes a receptor tyrosine kinase that plays a crucial role in embryonic development and cellular differentiation. ALK alterations can result from gene fusion, mutation, amplification, or overexpression in gastric adenocarcinoma. Fusion occurs when the ALK gene fuses with another gene, resulting in a chimeric protein with constitutive kinase activity and promoting oncogenesis. ALK mutations are less common but can also result in the activation of ALK signaling pathways. Targeted therapies for ALK variations in gastric adenocarcinoma have been developed, including ALK inhibitors that have shown promising results in pre-clinical studies. Future studies are needed to elucidate the ALK role in gastric cancer and to identify predictive biomarkers to improve patient selection for targeted therapy. Overall, ALK alterations are a relevant biomarker for gastric adenocarcinoma treatment and targeted therapies for ALK may improve patients' overall survival., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To evaluate the effects of supplementation with whey protein combined with vitamins C and E on inflammatory markers in hemodialysis (HD) patients., Design and Methods: This was a pioneer, randomized and double-blinded study. Patients were randomized into two groups and stratified by HD frequency. The supplementation group received 20 g of whey protein, 250 mg of vitamin C, and 600 IU of vitamin E; the placebo group, 20 g of rice flour, and microcrystalline cellulose capsules. The interventions were given after HD, 3 times a week, for 8 weeks. The inflammatory markers were assessed: interleukin (IL) IL-12p70, IL-10, IL-6, IL-8, and tumor necrosis factor alpha. For statistical analysis, the χ2 test, Student's t-test, Mann-Whitney test, analysis of variance for repeated two-way measurements, paired t test, and Wilcoxon test were performed. P < .05 was considered statistically significant., Results: Twenty-three patients completed the study. No significant differences were found in inflammatory markers when comparing the groups postintervention. In the intragroup was a decrease in IL-10 in the supplementation group after 8 weeks (P = .0382). IL-6 tended to decrease by 810.95% in the supplementation group and increased by 732.8% (nonsignificant) in the placebo group., Conclusion: Whey protein combined with vitamins C and E significantly reduced IL-10 in the supplementation group and could be beneficial to reduce IL-6 in HD patients. Future studies are suggested with a larger sample size, different supplementation doses, and longer interventions., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this scoping review was to evaluate the efficacy and safety of the use of systemic nonsteroidal immunomodulators (SNSI) for oral lichen planus (OLP) treatment., Materials and Methods: This review was conducted according to PRISMA-ScR guidelines and registered at PROSPERO (CRD42021243524). Consulted databases were Pubmed, Embase, Scopus, and Web of Science. The inclusion criteria was as follows: clinical trials, case series, prospective, and retrospective studies conducted with participants presenting OLP of any sex and age., Results: Thirty-two studies were selected, assessing 9 different SNSI: methotrexate, dapsone, levamisole, hydroxychloroquine, thalidomide, metronidazole, azathioprine, mycophenolate mofetil, and colchicine. Methotrexate and dapsone were the drugs with the best evidence among the options included, regarding number and quality of studies. Methotrexate resulted in significant improvement in the clinical condition and remission of symptoms, ranging between 63 and 93% of cases. Dapsone presented a similar effect to the use of topical corticosteroids and tacrolimus CONCLUSION: Among SNSI therapeutic options, methotrexate, and dapsone showed promising efficacy and safety. However, large-scale randomized clinical trials are still needed., Clinical Relevance: SNSI have been used in the treatment of recalcitrant OLP; however, so far, it is not clear which are the best options. This scoping review highlights the potential use of methotrexate and dapsone., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Detection of t(9;22), and consequent BCR::ABL1 fusion, is still a marker of worse prognosis for acute lymphoblastic leukemia (ALL), with resistance to tyrosine-kinase inhibitor therapy being a major obstacle in the clinical practice for this subset of patients. In this study, we investigated the effectiveness of targeting poly-ADP-ribose polymerase (PARP) in a model of BCR::ABL1 p190+ ALL, the most common isoform to afflict ALL patients, and demonstrated the use of experimental PARP inhibitor (PARPi), AZD2461, as a therapeutic option with cytotoxic capabilities similar to that of imatinib, the current gold standard in medical care. We characterized cytostatic profiles, induced cell death, and biomarker expression modulation utilizing cell models, also providing a comprehensive genome-wide analysis through an aCGH of the model used, and further validated PARP1 differential expression in samples of ALL p190+ patients from local healthcare institutions, as well as in larger cohorts of online and readily available datasets. Overall, we demonstrate the effectiveness of PARPi in the treatment of BCR::ABL1 p190+ ALL cell models and that PARP1 is differentially expressed in patient samples. We hope our findings help expand the characterization of molecular profiles in ALL settings and guide future investigations into novel biomarker detection and pharmacological choices in clinical practice.

Gastric cancer (GC) is among the most-diagnosed and deadly malignancies worldwide. Deregulation in cellular bioenergetics is a hallmark of cancer. Based on the importance of metabolic reprogramming for the development and cancer progression, inhibitors of cell metabolism have been studied as potential candidates for chemotherapy in oncology. Mebendazole (MBZ), an antihelminthic approved by FDA, has shown antitumoral activity against cancer cell lines. However, its potential in the modulation of tumoral metabolism remains unclear. Results evidenced that the antitumoral and cytotoxic mechanism of MBZ in GC cells is related to the modulation of the mRNA expression of glycolic targets SLC2A1, HK1, GAPDH, and LDHA. Moreover, in silico analysis has shown that these genes are overexpressed in GC samples, and this increase in expression is related to decreased overall survival rates. Molecular docking revealed that MBZ modifies the protein structure of these targets, which may lead to changes in their protein function. In vitro studies also showed that MBZ induces alterations in glucose uptake, LDH's enzymatic activity, and ATP production. Furthermore, MBZ induced morphologic and intracellular alterations typical of the apoptotic cell death pathway. Thus, this data indicated that the cytotoxic mechanism of MBZ is related to an initial modulation of the tumoral metabolism in the GC cell line. Altogether, our results provide more evidence about the antitumoral mechanism of action of MBZ towards GC cells and reveal metabolic reprogramming as a potential area in the discovery of new pharmacological targets for GC chemotherapy., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Gastric cancer (GC) is a highly heterogeneous, complex disease and the fifth most common cancer worldwide (about 1 million cases and 784,000 deaths worldwide in 2018). GC has a poor prognosis (the 5-year survival rate is less than 20%), but there is an effort to find genes highly expressed during tumor establishment and use the related proteins as targets to find new anticancer molecules. Data were collected from the Gene Expression Omnibus (GEO) bank to obtain three dataset matrices analyzing gastric tumor tissue versus normal gastric tissue and involving microarray analysis performed using the GPL570 platform and different sources. The data were analyzed using the GEPIA tool for differential expression and KMPlot for survival analysis. For more robustness, GC data from the TCGA database were used to corroborate the analysis of data from GEO. The genes found in in silico analysis in both GEO and TCGA were confirmed in several lines of GC cells by RT-qPCR. The AlphaFold Protein Structure Database was used to find the corresponding proteins. Then, a structure-based virtual screening was performed to find molecules, and docking analysis was performed using the DockThor server. Our in silico and RT-qPCR analysis results confirmed the high expression of the AJUBA , CD80 and NOLC1 genes in GC lines. Thus, the corresponding proteins were used in SBVS analysis. There were three molecules, one molecule for each target, MCULE-2386589557-0-6, MCULE-9178344200-0-1 and MCULE-5881513100-0-29. All molecules had favorable pharmacokinetic, pharmacodynamic and toxicological properties. Molecular docking analysis revealed that the molecules interact with proteins in critical sites for their activity. Using a virtual screening approach, a molecular docking study was performed for proteins encoded by genes that play important roles in cellular functions for carcinogenesis. Combining a systematic collection of public microarray data with a comparative meta-profiling, RT-qPCR, SBVS and molecular docking analysis provided a suitable approach for finding genes involved in GC and working with the corresponding proteins to search for new molecules with anticancer properties.

We present an abinitio study of the quasi-2D layered perovskite Sr 3 Hf 2 O 7 compound, performed within the framework of the density functional theory and lattice dynamics analysis. At high temperatures, this compound takes a I4/mmm centrosymmetric structure (S.G. n. 139); as the temperature is lowered, the symmetry is broken into other intermediate polymorphs before reaching the ground-state structure, which is the Cmc 2 1 ferroelectric phase (S.G. n. 36). One of these intermediate polymorphs is the Ccce structural phase (S.G. n. 68). Additionally, we have probed the C2/c system (S.G n. 15), which was obtained by following the atomic displacements corresponding to the eigenvectors of the imaginary frequency mode localized at the Γ-point of the Ccce phase. By observing the enthalpies at low pressures, we found that the Cmc 2 1 phase is thermodynamically the most stable. Our results show that the I4/mmm and C2/c phases never stabilize in the 0-20 GPa range of pressure values. On the other hand, the Ccce phase becomes energetically more stable at around 17 GPa, surpassing the Cmc 2 1 structure. By considering the effect of entropy and the constant-volume free energies, we observe that the Cmc 2 1 polymorph is energetically the most stable phase at low temperature; however, at 350 K, the Ccce system becomes the most stable. By probing the volume-dependent free energies at 19 GPa, we see that Ccce is always the most stable phase between the two structures and also throughout the studied temperature range. When analyzing the phonon dispersion frequencies, we conclude that the Ccce system becomes dynamically stable only around 19-20 GPa and that the Cmc 2 1 phase is metastable up to 30 GPa., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Aim: This study aimed to analyze the phylogenetic relationships between the ACE2 of humans and other animals and investigate the potential interaction between SARS-CoV-2 RBD and ACE2 of different species. Materials & methods: The phylogenetic construction and molecular interactions were assessed using computational models. Results & conclusion: Despite the evolutionary distance, 11 species had a perfect fit for the interaction between their ACE2 and SARS-CoV-2 RBD ( Chinchilla lanigera, Neovison vison , Rhinolophus sinicus, Emballonura alecto , Saccopteryx bilineata , Numida meleagris ). Among them, the avian N. meleagris was reported for the first time in this study as a probable SARS-CoV-2 host due to the strong molecular interactions. Therefore, predicting potential hosts for SARS-CoV-2 for understanding the epidemiological cycle and proposal of surveillance strategies., Competing Interests: The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed., (© 2023 Future Medicine Ltd.)

Bergenin is a glycosidic derivative of trihydroxybenzoic acid that was discovered in 1880 by Garreau and Machelart from the rhizomes of the medicinal plant Bergenia crassifolia (currently: Saxifraga crassifolia -Saxifragaceae), though was later isolated from several other plant sources. Since its first report, it has aroused interest because it has several pharmacological activities, mainly antioxidant and anti-inflammatory. In addition to this, bergenin has shown potential antimalarial, antileishmanial, trypanocidal, antiviral, antibacterial, antifungal, antinociceptive, antiarthritic, antiulcerogenic, antidiabetic/antiobesity, antiarrhythmic, anticancer, hepatoprotective, neuroprotective and cardioprotective activities. Thus, this review aimed to describe the sources of isolation of bergenin and its in vitro and in vivo biological and pharmacological activities. Bergenin is distributed in many plant species (at least 112 species belonging to 34 families). Both its derivatives (natural and semisynthetic) and extracts with phytochemical proof of its highest concentration are well studied, and none of the studies showed cytotoxicity for healthy cells.

Adequate adherence to the 2018 diet and exercise recommendations of the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) can possibly result in less oxidative stress, lower risk to chemo- and radiotoxicity, lower risk of relapse, and increased quality of life in breast cancer survivors. This observational study aims to investigate the influence of adherence to updated recommendations of the WCRF/AICR on oxidative stress biomarkers in women with breast cancer undergoing adjuvant treatment (AT). We hypothesized that adherence to WCRF/AICR recommendations is inversely related to oxidative damage biomarkers and directly associated with antioxidant status. Women (n = 78) were evaluated before (T0) and after AT. After collecting anthropometric, physical activity, and food consumption data, a standardized score of adherence to WCRF/AICR recommendations was applied. The sample was divided into low-medium adherence and high adherence groups. Blood samples were collected at both timepoints for oxidative stress biomarkers analysis. Multiple linear regression analyzes were applied to verify associations between WCRF/AICR score and biomarkers. We found that low-medium adherence to WCRF/AICR recommendations at T0 affected lower levels of reduced glutathione (P= .003) and higher levels of lipid hydroperoxides (P= .002) and plasma carbonylated proteins (P= .001) after AT. The WCRF/AICR score at T0 was inversely associated with changes in plasma carbonylated protein concentrations after AT (adjusted β = -0.359; P= .01). Our findings suggest that high WCRF/AICR score before and during AT may provide greater stability of antioxidant capacity and protection against exacerbated oxidative stress., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Colorectal cancer (CRC) is estimated as the third most incident cancer and second in mortality worldwide. Moreover, CRC metastasis reduces patients' survival rates. Thus, the study and identification of new compounds with anticancer activity selectively to tumor cells are encouraged in the CRC treatment. Naphtoquinones are compounds with several pharmacologic activities, including antitumoral properties. Therefore, this study aimed to investigate the anticancer mechanism of synthetic 8-Hydroxy-2-(P-Nitrothiophenol)-1,4-Naphthoquinone (CNN16) in colon cancer cell line HCT-116. CNN16 showed an IC 50 of 5.32 μM in HCT-116, and 9.36, 10.77, and 24.57 μM in the non-cancerous cells MRC-5, MNP-01, and PMBC, respectively, evaluated by the MTT assay. CNN16 showed an anticlonogenic effect in HCT-116 and induced cell fragmentation identified by flow cytometry analysis. Furthermore, we observed that CNN16 presented genotoxicity and induces reactive oxygen species (ROS) after 3 h of treatment visualized by alkaline comet assay and DCFH-DA dye fluorescence, respectively. Furthermore, CNN16 caused cellular membrane disruption, reduction in the mitochondrial membrane polarization, and the presence of apoptotic bodies and chromatin condensation was visualized by differential stained (HO/FD/PI) in fluorescent microscopy along with PARP1, TP53, BCL-2, and BAX analyzed by RT-qPCR. Results also evidenced inhibition in the migratory process analyzed by wound healing assay. Therefore, CNN16 can be considered as a potential new leader molecule for CRC treatment, although further studies are still necessary to comprehend the effects of CNN16 in in vivo models to evaluate the anti-migratory effect, and toxicology and assure compound safety and selectively., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Raquel Carvalho Montenegro reports financial support was provided by National Council for Scientific and Technological Development. Raquel Carvalho Montenegro has patent #BR1020180073850 pending to INPI - National Institute of Industrial Property., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The groundwork for malaria elimination does not currently consider the potential of Plasmodium zoonotic cycles that involve non-human primates (NHPs) in sylvatic environments. Since vivax malaria is less responsive to control measures, finding Plasmodium vivax infected NHPs adds even more concern., Methods: Both Free-living monkeys in forest fragments inside the urban area and captive monkeys from a local zoo had blood samples tested for Plasmodium species., Results: In this study, among the Neotropical monkeys tested, three (4.4%), one captive and two free-living, were found to be naturally infected by P. vivax., Conclusion: This important finding indicates that it is necessary to estimate the extent to which P. vivax NHP infection contributes to the maintenance of malaria transmission to humans. Therefore, the discussion on wildlife conservation and management must be incorporated into the malaria elimination agenda., (© 2022. The Author(s).)

Food aversions in women undergoing adjuvant chemotherapy for breast cancer may be linked to oxidative stress and gastrointestinal consequences underlying it, and diet possibly plays a role in this association. This follow-up study included 73 women with breast cancer treated in Florianopolis City, Brazil. Dietary antioxidant capacity-DaC (mmol/d), diet quality-Brazilian Healthy Eating Index Revised (BHEI-R score), and oxidative stress biomarkers were accessed before the treatment, and women were asked if they developed food aversions during adjuvant chemotherapy. Red meat was the main aversion-causing food reported (37.9%, n = 9). There was no difference in DaC, BHEI-R score, or oxidative stress biomarkers between women with no food aversion occurrence and those showing food aversions. A logistic regression adjusted model showed that women exhibiting higher BHEI-R scores were 1.08 times more likely to not develop food aversions during adjuvant chemotherapy ( p = 0.041). In summary, this innovative investigation showed that diet quality before adjuvant chemotherapy may influence the non-occurrence of food aversion. Considering this, the result opens new areas for early nutritional interventions, focusing on reducing the occurrence of food aversions and consequently benefiting women with breast cancer by having better outcomes in oncologic treatment.

Despite advances in cancer chemotherapy, gastric cancer (GC) continues to have high recurrence rates and poor prognosis with limited treatment options. Understanding the etiology of GC and developing more effective, less harmful therapeutic approaches are vital and urgent. Therefore, this work describes a novel kinase target in malignant gastric cells as a potential therapeutic strategy. Our results demonstrate that among 147 kinase inhibitors (KI), only three molecules were significantly cytotoxic for the AGP-01 cell line. Hence, these three molecules were further characterized in their cellular mode of action. There was significant cell cycle impairment due to the expression modulation of genes such as TP53 , CDKN1A , CDC25A , MYC , and CDK2 with subsequent induction of apoptosis. In fact, the Gene Ontology analysis revealed a significant enrichment of pathways related to cell cycle regulation (GO:1902749 and GO:1903047). Moreover, the three selected KIs significantly reduced cell migration and Vimentin mRNA expression after treatment. Surprisingly, the three KIs share the same target, ALK and INSR , but only the ALK gene was found to have a high expression level in the gastric cancer cell line. Additionally, lower survival rates were observed for patients with high ALK expression in TCGA-STAD analysis. In summary, we hypothesize that ALK gene overexpression can be a promising biomarker for prognosis and therapeutic management of gastric adenocarcinoma.

Chronic myeloid leukemia (CML) is caused by constitutively active fusion protein BCR-ABL1, and targeting ABL1 is a promising therapy option. Imatinib, dasatinib, and nilotinib have all been shown to work effectively in clinical trials. ABL1 mutations, particularly the T315I gate-keeper mutation, cause resistance in patients. As a result, broad-spectrum ABL1 medicines are desperately needed. In order to screen potential drugs targeting CML, mebendazole (MBZ) was subjected to the in vitro test against CML cell lines (K562 and FEPS) and computational assays. The antiproliferative effect of MBZ and the combination with tyrosine kinase inhibitors (TKIs) was tested using end-point viability assays, cell cycle distribution analysis, cell membrane, and mitochondrial dyes. By interrupting the cell cycle and causing cell death, MBZ and its combination with imatinib and dasatinib have a significant antiproliferative effect. We identified MBZ as a promising "new use" drug targeting wild-type and mutant ABL1 using molecular docking. Meanwhile, we determined which residues in the allosteric site are important in ABL1 drug development. These findings may not only serve as a model for repositioning current authorized medications but may also provide ABL1-targeted anti-CML treatments a fresh lease of life., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Daniel, Mesquita, Da Silva, de Souza, Lima, de Oliveira, de Moraes, Moreira-Nunes, Burbano, Zanatta and Montenegro.)

Objective: To assess the prevalence of skin lesions and evaluate the clinical and sociodemographic factors associated with their presence in hospitalised patients., Method: This descriptive, cross-sectional, correlational study was performed in inpatient units and intensive care units of a cancer hospital in São Paulo, Brazil, after approval by the Institutional Research Ethics Committee. Data from hospitalised adult patients with cancer were collected during physical examinations and from medical records. A Chi-squared test, univariate analysis, a logistic regression model with results expressed as odds ratio (OR) and 95% confidence intervals (CI), and Classification and Regression Tree (CART) analysis were used to evaluate the data., Results: Of 341 patients, 80 had skin lesions, equating to an overall prevalence of 23.5%. The skin lesions included pressure injuries (10%), incontinence-associated dermatitis (6.7%), skin tears (6.5%), malignant wounds (3.8%) and complicated surgical wounds (3.2%). The factors associated with skin lesions in cancer patients were the use of disposable nappies (OR: 4.436) and age (59.1±15.1 years), according to the CART analysis, and the wearing of nappies (OR: 4.466, p<0.001), presence of ecchymosis (OR: 2.532, p<0.001) and infection (OR: 6.449, p=0.040), according to multiple regression analysis., Conclusion: This study contributed to knowledge about prevalence and associated factors of skin lesions in hospitalised patients with cancer, allowing the implementation of preventive measures.

Gastric cancer (GC) is among the deadliest cancers worldwide despite available therapies, highlighting the need for novel therapies and pharmacological agents. Metabolic deregulation is a potential study area for new anticancer targets, but the in vitro metabolic studies are controversial, as different ranges of glucose used in the culture media can influence results. In this study, we evaluated cellular viability, glucose uptake, and LDH activity in gastric cancer cell lines when exposed to different glucose concentrations: high (HG, 25mM), low (LG, 5.5mM), and free (FG, 0mM) glucose media. Moreover, we evaluated how glucose variations may influence cellular phenotype and the expression of genes related to epithelial-mesenchymal transition (EMT), metabolism, and cancer development in metastatic GC cells (AGP-01). Results showed that metastatic cells exposed to FG medium evidenced higher alterations when compared to other cell lines. Most phenotypic assays did not show difference when exposed to either HG or LG media. However, gene expression profile of cells exposed to LG revealed differences in mRNA levels of metabolism-related genes when compared to HG medium. According to our results, we recommend using LG medium for metabolic studies since the glucose concentration is closer to physiological levels. These findings point out new relevant targets in metabolic reprogramming that can be alternatives to current chemotherapies in patients with metastatic GC., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The multidrug resistance (MDR) phenotype is one of the major obstacles in the treatment of chronic myeloid leukemia (CML) in advantage stages such as blast crisis. In this scenario, more patients develop resistance mechanisms during the course of the disease, making tyrosine kinase inhibitors (TKIs) target therapies ineffective. Therefore, the aim of the study was to examine the pharmacological role of CNN1, a para-naphthoquinone, in a leukemia multidrug resistant cell line. First, the in vitro cytotoxic activity of Imatinib Mesylate (IM) in K-562 and FEPS cell lines was evaluated. Subsequently, membrane integrity and mitochondrial membrane potential assays were performed to assess the cytotoxic effects of CNN1 in K-562 and FEPS cell lines, followed by cell cycle, alkaline comet assay and annexin V-Alexa Fluor® 488/propidium iodide assays (Annexin/PI) using flow cytometry. RT-qPCR was used to evaluate the H2AFX gene expression. The results demonstrate that CNN1 was able to induce apoptosis, cell membrane rupture and mitochondrial membrane depolarization in leukemia cell lines. In addition, CNN1 also induced genotoxic effects and caused DNA fragmentation, cell cycle arrest at the G2/M phase in leukemia cells. No genotoxicity was observed on peripheral blood mononuclear cells (PBMC). Additionally, CNN1 increased mRNA levels of H2AFX. Therefore, CNN1 presented anticancer properties against leukemia multidrug resistant cell line being a potential anticancer agent for the treatment of resistant CML.

Introduction: The consumption of yerba mate (YM), a source of antioxidants, in a fasted state increases fatty acid oxidation (FAT ox ) during low-moderate-intensity exercise and improves performance in high-intensity exercise. However, the impact of a pre-exercise carbohydrate (CHO) meal on YM effects during exercise is unknown., Objective: We investigated the effects of yerba mate drink (YMD) consumed in the fasted state (YMD-F) or after a CHO meal (YMD-CHO) on measurements of metabolism, performance, and blood oxidative stress markers in cycling exercise., Methods: In a randomized, repeated-measures, crossover design, eight trained male cyclists ingested (i) YMD-CHO, (ii) YMD-F, or (iii) control-water and CHO meal (Control-CHO). The YMD (an infusion of 5 g of ultrarefined leaves in 250 mL of water) was taken for 7 days and 40 min before exercise. CHO meal (1 g/kg body mass) was consumed 60 min before exercise. The cycling protocol included a 40-min low-intensity (~ 53% V̇O 2peak ) constant load test (CLT); a 20-min time trial (TT); and 4 × 10-s all-out sprints. Blood samples and respiratory gases were collected before, during, and/or after tests., Results: During CLT, YMD-CHO increased FAT ox  ~ 13% vs. YMD-F (P = 0.041) and ~ 27% vs. Control-CHO (P < 0.001). During TT, YMD-CHO increased FAT ox  ~ 160% vs. YMD-F (P < 0.001) and ~ 150% vs. Control-CHO (P < 0.001). Power output during TT improved ~ 3% (P = 0.022) in YMD-CHO vs. Control-CHO and was strongly correlated with changes in serum total antioxidant capacity (r = -0.87) and oxidative stress index (r = 0.76) at post-exercise in YMD-CHO. Performance in sprints was not affected by YMD., Conclusion: CHO intake did not negate the effect of YMD on FAT ox or TT performance. Instead, a synergism between the two dietary strategies may be present. Clinical Trial Registration NCT04642144. November 18, 2020. Retrospectively registered., (© 2022. The Author(s).)

Background: The aim of this study was to identify variables related to organ donation that can contribute to the development of best practices in planning and conducting family interviews by health professionals., Methods: This descriptive and prospective study of quantitative approach was conducted at 2 southern Brazil health institutions referenced in organ donation. Data collection occurred between 2018 and 2019 by health professionals who conduct family interviews using validated instruments that assessed the stages of the interview. Analysis was performed by means of the proportions of the studied variables associated with the donation authorization categories per the χ 2 test. The significance level adopted was 0.05., Results: The variables that presented the highest level of significance in the correlation with the prevalence of family authorization for organ donation included the following: communication with the family about the results of each test in the brain death diagnostic protocol; identification of whether the family understood the information about the death; presence of a member of the transplantation commission who had training to communicate information about organ donation; presence of a family member who had power to authorize the donation; and the interval between the communication of death and information about organ donation., Conclusions: The study presents important gaps that can be filled by health teams and hospitals in order to improve the welcoming and respect for families, as well as the organ donation rates. It is important to understand that each family is unique when facing mourning, and to distance the communication of death from the discussion about organ donation is an act of respect and empathy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The increasing numbers of cancer cases worldwide and the exceedingly high mortality rates of some tumor subtypes raise the question about if the current protocols for cancer management are effective and what has been done to improve upon oncologic patients' prognoses. The traditional chemo-immunotherapy options for cancer treatment focus on the use of cytotoxic agents that are able to overcome neoplastic clones' survival mechanisms and induce apoptosis, as well as on the ability to capacitate the host's immune system to hinder the continuous growth of malignant cells. The need to avert the highly toxic profiles of conventional chemo-immunotherapy and to overcome the emerging cases of tumor multidrug resistance has fueled a growing interest in the field of precision medicine and targeted molecular therapies in the last couple of decades, although relatively new alternatives in oncologic practices, the increased specificity, and the positive clinical outcomes achieved through targeted molecular therapies have already consolidated them as promising prospects for the future of cancer management. In recent years, the development and application of targeted drugs as tyrosine kinase inhibitors have enabled cancer treatment to enter the era of specificity. In addition, the combined use of targeted therapy, immunotherapy, and traditional chemotherapy has innovated the standard treatment for many malignancies, bringing new light to patients with recurrent tumors. This article comprises a series of clinical trials that, in the past 5 years, utilized kinase inhibitors (KIs) as a monotherapy or in combination with other cytotoxic agents to treat patients afflicted with solid tumors. The results, with varying degrees of efficacy, are reported.

Introduction: To identify the prevalence of infection in the urban area of the capital city of Belém, Brazil, the Laboratory of Virology of the Federal University of Pará implemented, as a public service, serological screening for human T-lymphotropic viruses 1 and 2 (HTLV-1/2) infection and, if necessary, counseling service and referral to specialized medical care. The project is funded by the National Council of Science and Technology, the Ministry of Health of Brazil and the Pan American Health Organization., Methods: From January 2020 to June 2021, 1,572 individuals of both sexes were approached to answer a questionnaire and were tested using an enzyme immunoassay (Murex HTLV-I+II, DiaSorin, Dartford, UK). Seropositive samples were confirmed as HTLV-1 and HTLV-2 infection by line immunoassay (INNO-LIA ® HTLV I/II Score, Fujirebio, Japan) and/or by real-time polymerase chain reaction. G and Fisher's exact tests were applied to identify the association between epidemiological characteristics and HTLV-1/2 infection., Results: Of the 1,572 screened individuals, 63.74% were females between the ages of 30 and 59 years (49.04%). Infection was confirmed in six individuals (0.38%), among whom three (0.19%) were infected with HTLV-1 and three with HTLV-2 (0.19%). Blood transfusion before 1993 was the main risk factor associated with the route of exposure to the virus ( p = 0.0442). The infected individuals were referred to a counseling session with a nursing professional, and two patients who manifested signs and symptoms suggestive of myelopathy associated with HTLV were referred to a neurologist., Conclusion: The implementation of the screening service revealed the occurrence of moderate endemicity of HTLV-1/2 in Belém, reinforcing the importance of continuing the service as a means of establishing an early diagnosis and providing counseling as a measure to prevent and control viral transmission in the general population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lopes, de Sousa, Carvalho Gomes, Vallinoto, de Lima, Lima, Freitas, Feitosa, Rangel da Silva, Machado, Aben-Athar, Maia da Silva, Cayres Vallinoto and Vallinoto.)

Bothrops spp. is responsible for about 70% of snakebites in Brazil, causing a diverse and complex pathophysiological condition. Bothrops leucurus is the main species of medical relevance found in the Atlantic coast in the Brazilian Northeast region. The pathophysiological effects involved B. leucurus snakebite as well as the organism's reaction in response to this envenoming, it has not been explored yet. Thus, edema was induced in mice paw using 1.2, 2.5, and 5.0 μg of B. leucurus venom, the percentage of edema was measured 30 min after injection and the blood plasma was collected and analyzed by shotgun proteomic strategy. We identified 80 common plasma proteins with differential abundance among the experimental groups and we can understand the early aspects of this snake envenomation, regardless of the suggestive severity of an ophidian accident. The results showed B. leucurus venom triggers a thromboinflammation scenario where family's proteins of the Serpins, Apolipoproteins, Complement factors and Component subunits, Cathepsins, Kinases, Oxidoreductases, Proteases inhibitors, Proteases, Collagens, Growth factors are related to inflammation, complement and coagulation systems, modulators platelets and neutrophils, lipid and retinoid metabolism, oxidative stress and tissue repair. Our findings set precedents for future studies in the area of early diagnosis and/or treatment of snakebites. SIGNIFICANCE: The physiopathological effects that the snake venoms can cause have been investigated through classical and reductionist tools, which allowed, so far, the identification of action mechanisms of individual components associated with specific tissue damage. The currently incomplete limitations of this knowledge must be expanded through new approaches, such as proteomics, which may represent a big leap in understanding the venom-modulated pathological process. The exploration of the complete protein set that suffer modifications by the simultaneous action of multiple toxins, provides a map of the establishment of physiopathological phenotypes, which favors the identification of multiple toxin targets, that may or may not act in synergy, as well as favoring the discovery of biomarkers and therapeutic targets for manifestations that are not neutralized by the antivenom., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Our goal was to analyze the outcome of infection and response to benznidazole (BZ) treatment in mice intragastrically inoculated with trypomastigotes forms of Trypanosoma cruzi from different origins., Methods: Twenty-four Swiss mice were divided in two groups and inoculated, by gavage, with 1 × 10 4 blood trypomastigotes (BT) or insect-derived metacyclic trypomastigotes (IT) of AM14 strain (T. cruzi IV). Half of the animals of each group were treated with BZ (TBZ), from 10 to 30th days after the inoculation, and the other constituted the untreated control groups (NT). After the etiological treatment, all mice were immunosuppressed with cyclophosphamide for three weeks. Parasitological and molecular parameters, infectivity, cumulative mortality, and reactivation post-immunosuppression rates were obtained., Results: Animals inoculated with BT showed lower pre-patent period and early day of the maximum parasitemia, as well as a higher maximum peak of parasitemia than the IT animals. However, both, BT and IT animals, did not respond to BZ treatment (0.0% of cure)., Conclusion: We conclude that the infective form influences in the outcome of infection, but not the response to the etiological treatment in mice intragastrically infected with the T. cruzi IV strain studied., (© 2021. Witold Stefański Institute of Parasitology, Polish Academy of Sciences.)

Acute Lymphoblastic Leukemia (ALL) is a neoplasm of the hematopoietic system defined as a clonal expansion of an abnormal lymphoid precursor cell. It mostly affects children under five years of age and is the most common tumor to afflict pediatric patients. The expression of the human telomerase gene ( hTERT ) in patients with ALL has been studied as a biomarker and could become a new therapeutic target. We evaluate the role of hTERT gene expression in ALL pediatric patients, through quantitative real-time PCR technique, and the possible correlation between hTERT expression and clinical variables: gender, age, white blood cells (WBC), gene fusions, and immunophenotyping. The analysis between healthy controls and ALL patients ( N = 244) was statistically significant ( p < 0.001), demonstrating hTERT overexpression in these patients. In comparison with the usual set of clinical variables, the data were not statistically significant ( p > 0.05), indicating that hTERT is equally overexpressed among patients regardless of gender, age, gene fusions, and immunophenotyping. Moreover, patients who presented a higher hTERT expression level had a significant ( p < 0.0001) lower overall survival rate. In summary, hTERT expression emerges as an important molecular pathway in leukemogenesis regardless patient's clinical variables, thus, the data here presented pointed it as a valuable biomarker in pediatric acute lymphoblastic leukemia and a promising target for new therapeutic and prognostic measures.

Cancer is still a major barrier to life expectancy increase worldwide, and hematologic neoplasms represent a relevant percentage of cancer incidence rates. Tumor dependence of continuous proliferative signals mediated through protein kinases overexpression instigated increased strategies of kinase inhibition in the oncologic practice over the last couple decades, and in this review, we focused our discussion on relevant clinical trials of the past five years that investigated kinase inhibitor (KI) usage in patients afflicted with relapsed/refractory (R/R) hematologic malignancies as well as in the pharmacological characteristics of available KIs and the dissertation about traditional chemotherapy treatment approaches and its hindrances. A trend towards investigations on KI usage for the treatment of chronic lymphoid leukemia and acute myeloid leukemia in R/R settings was observed, and it likely reflects the existence of already established treatment protocols for chronic myeloid leukemia and acute lymphoid leukemia patient cohorts. Overall, regimens of KI treatment are clinically manageable, and results are especially effective when allied with tumor genetic profiles, giving rise to encouraging future prospects of an era where chemotherapy-free treatment regimens are a reality for many oncologic patients.

Objectives: The aim of this systematic review was to assess the efficacy and safety of topical non-steroidal immunomodulators (TNSIs) for oral lichen planus (OLP) treatment., Materials and Methods: A search strategy designed for this purpose retrieved 1156 references. After analysis of titles and abstracts, 75 studies were selected for full-text analysis. Only randomized controlled clinical trials were selected, resulting in 28 studies included for qualitative and quantitative analysis., Results: The meta-analysis showed similar benefits in clinical response and symptom resolution between tacrolimus 0.1% and pimecrolimus 1% in comparison to topical steroids (TS). Pimecrolimus showed superior efficacy of clinical response but not for symptom resolution compared to placebo. Tacrolimus and pimecrolimus showed better performance preventing symptom relapse, while pimecrolimus also prevented clinical relapse better than TS. Cyclosporine was superior to placebo; however, TS showed better efficacy of clinical response. Thalidomide and retinoid were assessed in only one trial each, and both showed similar efficacy to TS. Rapamycin also presented similar clinical response to TS; however, the later showed greater reduction of symptoms. Mycophenolate mofetil 2% mucoadhesive was no better than placebo. No serious adverse effects have been reported. Cyclosporine showed a higher frequency and variety of adverse effects., Conclusions: Topical tacrolimus and pimecrolimus are safe and effective alternatives for OLP treatment., Clinical Relevance: TS are usually the first choice for OLP treatment. Because some oral lesions may have a low response to treatment with TS, more topical therapeutic options, such as TNSIs, should be considered before systemic steroids are used., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study proposed to investigate the effect of Ilex paraguariensis infusion on the absorption of non-heme iron in hereditary hemochromatosis (HH) patients with the HFE genotype. A two-way randomized, controlled, crossover trial was conducted on patients, aged 29-69 years, undergoing maintenance therapy. Fourteen HFE-HH patients ingested a meal containing 11.4 mg iron and 200 mL either of water (control) or of Ilex paraguariensis leaf infusion. The beverages were offered in random order, at intervals separated by a washout period of 7 days. Active surveillance showed no adverse effects. Blood samples were drawn shortly before and 1, 2, 3, and 4 h after the meal for serum iron measurement. A significant reduction in the postprandial serum iron was observed for HH patients after intake of the Ilex paraguariensis infusion (area under the curve (AUC) expressed as mean ± SEM: 173.3 ± 44.7 μmol h -1 L -1 ) compared to water (1449.4 ± 241.5 μmol h -1 L -1 ) (p < 0.001). In summary, intake of Ilex paraguariensis leaf infusion significantly inhibited the absorption of iron in patients with HH and, therefore, should be considered as a potential adjuvant for iron overload control.

Purpose: Whey protein has antioxidant properties through its amino acid cysteine, which enhances the biosynthesis of glutathione, the most abundant antioxidant non-protein in mammalians. Glutathione influences vitamin C recycling and increases its protective effect on oxidative stress (OS). The aim of this study was to analyse the effect of whey protein and vitamin C supplementation on OS biomarkers in chronic haemodialysis (HD) patients., Methods: This pioneer trial was a randomised, double-blind, pilot study in patients from a dialysis clinic. Patients were randomised into three groups (1:1:1) and stratified by HD frequency (2 or 3 times/week). Sachets containing protein powder (20.0 g) with/without vitamin C (0.25 g) or placebo (20.0 g of white rice flour) with vitamin C (0.25 g) were supplemented after each HD session, 3 times/week for 8 weeks. Blood samples were collected at the baseline period and after 8 weeks for the measurement of reduced glutathione (GSH), oxidised glutathione (GSSG), the GSH:GSSG ratio, malondialdehyde, vitamin C, and glutathione peroxidase-1., Results: Twenty-two patients were enrolled, of which 18 concluded the trial, 6 per group (18.2%, n = 4 losses during follow-up). The vitamin C group presented decreased GSH levels after supplementation (p = 0.053) and a decreasing tendency in the GSH:GSSG ratio (non-statistically significant), while MDA levels significantly decreased only in the whey protein-supplemented groups (p ≤ 0.05)., Conclusion: The results suggest a pro-oxidant effect of 0.25 g of vitamin C alone in chronic HD patients., Clinical Trial Registration: https://ensaiosclinicos.gov.br/ , RBR-65b8f4., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Aurora kinases are a family of serine/threonine protein kinases that play a central role in eukaryotic cell division. Overexpression of aurora kinases in cancer and their role as major regulators of the cell cycle quickly inspired the idea that their inhibition might be a potential pathway when treating oncologic patients. Over the past couple of decades, the search for designing and testing of molecules capable of inhibiting aurora activities fueled many pre-clinical and clinical studies. In this study, data from the past 10 years of in vitro and in vivo investigations, as well as clinical trials, utilizing aurora kinase inhibitors as therapeutics for hematological malignancies were compiled and discussed, aiming to highlight potential uses of these inhibitors as a novel monotherapy model or alongside conventional chemotherapies. While there is still much to be elucidated, it is clear that these kinases play a key role in oncogenesis, and their manageable toxicity and potentially synergistic effects still render them a focus of interest for future investigations in combinatorial clinical trials., Competing Interests: The Authors declare no conflicts of interest regarding this study., (Copyright 2021, International Institute of Anticancer Research.)

Background/aim: Experimental oncology commonly uses cells as oncological models, providing a framework for the testing of drugs, and investigation of cytotoxicity, mutagenesis and carcinogenesis. Investigations into poly-ADP-ribose polymerase 1 (PARP1) inhibition have become ever more relevant due to its approval as a therapeutic option for tumors with BRCA1/2 DNA repair-associated mutation and the seemingly high PARP expression levels in some tumor subtypes. In this study, we aimed to determine PARP1 gene expression of different hematological cancer-derived cell lineages and compare them to that of normal cell lines., Materials and Methods: PARP1 gene expression in seven different neoplastic lineages, representing three different hematological disorders (chronic myeloid leukemia, Burkitt lymphoma and acute lymphoblastic leukemia), was quantified by quantitative real-time polymerase chain reaction., Results: All hematological malignant lineages in this study overexpressed PARP1 when compared to the normal cell line MRC-5, with Burkitt's lymphoma cells having the highest expression values (fold change: 93)., Conclusion: Overexpression of PARP1 in hematological malignant lineages is a finding of crucial importance to future studies exploring possible cellular oncogenic pathways and supports investigations into the effectiveness of PARP1 inhibitors against hematological disorders., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)