This work explores the synthesis, physicochemical characterization, and in vivo biocompatibility of iron-based layered double hydroxides (LDHs) with molar ratio M2+/(Fe3+ + Al3+) equal to 2, ...Fe3+/Al3+ equal to 1, and chloride anions as charge-compensating ion (abbreviated Mg4FeAl-Cl and Zn4FeAl-Cl) prepared by the coprecipitation method. The higher structural organization of Zn4FeAl-Cl in comparison to Mg2+ analogous material was noticed by X-ray diffraction and scanning electron microscopy images. Biocompatibility of LDH was evaluated by intramuscular implantation in rats. Tablets of M4FeAl-Cl (M = Mg, Zn) were readily identified macroscopically after 7 and 28 days of implantation, denoting slow dissolution in the internal medium; adjacent to the tablets, blood flow was preserved without tortuosity or pathological dilatations, according to the Sidestream Dark Field Imaging technique. The histological analysis showed no inflammatory response and the presence of angiogenesis and tissue remodeling with the reconstruction of the extracellular matrix and cells around the tablets, besides the induction of collagen type-I formation. Prussian blue histochemical reaction suggested higher solubility of Mg4FeAl-Cl in the extracellular matrix compared to zinc LDH. Considering the positive biocompatibility results obtained for M4 IIFeAl-LDH materials, experiments were conducted to intercalate the anti-inflammatory naproxen, as a model drug, into the iron-based LDHs (M4 IIFeAl-NAP). The release profile of NAP in phosphate buffer showed 90% of the drug delivered after about 80 h. However, divalent metal leaching was verified mainly for Mg-LDH (around 50%) when compared to Zn2+ (around 1%). Iron-based LDHs have great potential for medical and technological applications as local drug delivery biomaterials exhibiting biocompatibility and biointegration properties.
The cytokine storm in SARS-CoV-2 infection contributes to the onset of inflammation and target-organ damage. The endothelium is a key player in COVID-19 pathophysiology and it is an important target ...for cytokines. Considering that cytokines trigger oxidative stress and negatively impact endothelial cell function, we sought to determine whether serum from individuals with severe COVID-19 decreases endothelial cells' main antioxidant defense, i.e., the antioxidant transcriptional factor Nrf2. Human umbilical vein endothelial cells (HUVECs) were incubated with serum from patients with severe COVID-19 at different time points and the effects on redox balance and Nrf2 activity were determined. Serum from individuals with COVID-19 increased oxidant species, as indicated by higher DHE (dihydroethydine) oxidation, increased protein carbonylation, and induced mitochondrial reactive oxygen species (ROS) generation and dysfunction. Serum from patients with COVID-19, but not serum from healthy individuals, induced cell death and diminished nitric oxide (NO) bioavailability. In parallel, Nrf2 nuclear accumulation and the expression of Nrf2-targeted genes were decreased in endothelial cells exposed to serum from individuals with COVID-19. In addition, these cells exhibited higher expression of Bach-1, a negative regulator of Nrf2 that competes for DNA binding. All events were prevented by tocilizumab, an IL-6 receptor blocker, indicating that IL-6 is key to the impairment of endothelial antioxidant defense. In conclusion, endothelial dysfunction related to SARS-CoV-2 infection is linked to decreased endothelial antioxidant defense via IL-6-dependent mechanisms. Pharmacological activation of Nrf2 may decrease endothelial cell damage in individuals with severe COVID-19.
We demonstrate that endothelial cell dysfunction in SARS-CoV-2-infected individuals is linked to decreased activity of the major antioxidant system regulator, the Nrf2 transcription factor. We provide evidence that this phenomenon relies on IL-6, an important cytokine involved in the pathophysiology of COVID-19. Our data support the view that Nrf2 activation is a potential therapeutical strategy to prevent oxidative stress and vascular inflammation in severe cases of COVID-19.
Scorpion envenomation represents an important health problem in many parts of the world, due to the high number and severity of accidents. Recent studies demonstrated that some species can produce ...venoms with genetic damage potential. Here, we evaluated whether Tityus stigmurus venom causes genetic damage in blood and testicular cells of Swiss mice. We also analyzed the effect of the venom on the number of spermatogenic lineage cells. Five groups of mice received 0.387 mg/kg of the venom, intraperitoneally; one group received saline solution (control group). Blood and testicular cells were collected for comet assay and histological analysis at different times after treatment (1, 2, 6, 12, and 48 h). Blood was also collected 48 h after treatment for the micronucleus test in erythrocytes. Histological analysis was performed by counting cells of the spermatogenic lineages; the nuclear area of elongated spermatocytes was also evaluated. Treatment with the venom induced DNA damage that endured from 1 h to 48 h, as confirmed by the comet assay. The micronucleus test demonstrated that the venom induced mutations in erythrocytes. The number of spermatogonia and rounded spermatids decreased in some groups; the number of elongated spermatids increased, and their nuclear size decreased 1 h after treatment. Genetic damage can be caused directly by the venom, but we suggested that reactive oxygen species that result from inflammatory process caused by the envenomation may have an important role in the DNA damage. Genetic damage and apoptosis may explain the changes in the number of spermatogenic cells. Furthermore, the decrease in nuclear area may result from chromatin loss. Genetic damage in testicular cells, associated with alterations in the number and morphology of spermatogenic cells, can result in reproduction disorders in animals, or humans, stung by T. stigmurus.
•Tityus stigmurus venom induces DNA damage in blood and testicular cells of mice.•The venom also induces mutations in blood of mice as seen by micronucleus test.•Number and nuclear morphology of spermatogenic lineage is altered by the venom.•Tityus stigmurus sting may result in reproductive disorders in animals and humans.
Abstract
Summary
To unlock the full potential of genome data and to enhance data interoperability and reusability of genome annotations we have developed SAPP, a Semantic Annotation Platform with ...Provenance. SAPP is designed as an infrastructure supporting FAIR de novo computational genomics but can also be used to process and analyze existing genome annotations. SAPP automatically predicts, tracks and stores structural and functional annotations and associated dataset- and element-wise provenance in a Linked Data format, thereby enabling information mining and retrieval with Semantic Web technologies. This greatly reduces the administrative burden of handling multiple analysis tools and versions thereof and facilitates multi-level large scale comparative analysis.
Availability and implementation
SAPP is written in JAVA and freely available at https://gitlab.com/sapp and runs on Unix-like operating systems. The documentation, examples and a tutorial are available at https://sapp.gitlab.io.
Purpose
Detecting potential drug interactions can lead to early interventions that protect patients from serious drug-related problems. The aim of this study was to evaluate the agreement among the ...lists of warfarin interactions provided by five information sources.
Methods
The lists of warfarin interactions and the corresponding severity ratings and documentation levels presented by the three compendia and by the World Health Organization (WHO) Model Formulary were all compared, and each list was compared to that provided on the package insert of Marevan, a brand of warfarin. The compendia used were:
Drug Interaction Facts
,
Drug Interactions: Analysis and Management
and DRUG–REAX. A kappa coefficient was used to calculate the agreement among the sources.
Results
A total of 537 interactions were listed. Only 13 (2.4%) were common to the five sources. The global Fleiss’ kappa coefficient was −0.0080, which indicated poor agreement. Eleven warfarin interactions appeared only in the Marevan package insert. Importantly, 243 interactions (45.3% of the total) were deemed significant in at least one compendium. Only two warfarin interactions were reported as critical by all three compendia and by WHO. The most critical interactions cited by the compendia were missing from the package insert.
Conclusions
Poor agreement was found among five sources listing warfarin interactions. Potentially severe clinical consequences might occur due to these discrepant recommendations. Finally, the lack of standard terminology and clinical guidance, as well as the possible inaccuracy of severity ratings and documentation might contribute to heterogeneous procedures in clinical practice.
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•Amberlite HPR1100 can remove phenolic compounds from real olive mill wastewater.•Different adsorption behaviours for real and synthetic olive mill wastewater.•Acetone was the solvent ...that led to higher recovery efficiencies.•Adsorption is a feasible technology for phenolics recovery.
Olive mill wastewater (OMW) is rich in valuable compounds such as phenolic compounds. Amberlite@HPR1100 was applied as adsorbent to recover these added-value compounds from OMW. For synthetic OMW, Langmuir isotherm and pseudo-second order kinetic model were able to predict the experimental data instead for real effluent, were the Freundlich isotherm and the pseudo-first order kinetic model the best fits. The continuous process was also studied, for real OMW the tbp, tst and tex were 1.27 min, 84.4 min and 575 min, respectively. After 645 min of adsorption, 42 % of phenolic content was adsorbed into the resin. An industrial column for recovering phenolic compounds from OMW was designed, which should have around 5 m and 0.6 m of height and diameter, respectively, filled with 112 kg of resin (dry basis). The desorption process for real OMW with acetone 80 % recovery was accomplished after 5 h of contact.
Several cases of food-borne acute Chagas disease (ACD) have been reported in the Brazilian Amazon so far. Up to 2004, the occurrence of ACD by oral transmission, associated with food consumption, was ...rare. Recent cases of ACD in Brazil have been attributed to the consumption of juice from the açai palm containing reservoir animals or insect vectors waste, infected with Trypanosoma cruzi. This study aimed to determine the T. cruzi contamination rate and to genotype the parasite in food samples prepared from açai, which are commercialized in Rio de Janeiro and the Pará States in Brazil.
The amplificability of DNA extracted from açai samples, and T. cruzi and Triatominae detection were performed by conventional PCR. Molecular characterization was done by multilocus PCR analysis, to determine the parasite discrete type units (DTUs) based on the size of PCR products in agarose gels, using the intergenic region of the spliced leader (SL), 24 Sα rDNA and nuclear fragment A10 as targets.
From the 140 samples of açai-based products analyzed, T. cruzi DNA was detected in 14 samples (10%); triatomine DNA was detected in one of these 14 samples. The parasite genotyping demonstrated that food samples containing açai showed a mixture of T. cruzi DTUs with TcIII, TcV and TcI prevailing.
In this study, the molecular detection and identification of T. cruzi from açai-based manufactured food samples, was performed for the first time. Although parasite DNA is a marker of possible contamination during food manufacturing, our findings do not indicate that açai is a source of Chagas disease via oral transmission per se, as live parasites were not investigated. Nevertheless, a molecular approach could be a powerful tool in the epidemiological investigation of outbreaks, supporting previous evidence that açai-based food can be contaminated with T. cruzi. Furthermore, both food quality control and assessment of good manufacturing practices involving açai-based products can be improved, assuring the safety of açai products.
The bacterial enzyme asparaginase is the main treatment option for acute lymphoblastic leukemia. However, it causes side effects, such as immunological reactions, and presents undesirable glutaminase ...activity. As an alternative, we have been studying asparaginase II from
, coded by
gene, which was cloned and expressed in
The recombinant asparaginase (ASP) presented antileukemic activity and a glutaminase activity 100 times lower in comparison to its asparaginase activity. In this work, we describe the development of a delivery system for ASP via its covalent attachment to functionalized polyethylene glycol (PEG) polymer chains in the outer surface of liposomes (ASP-enzymosomes). This new delivery system demonstrated antiproliferative activity against K562 (chronic myeloid leukemia) and Jurkat (acute lymphocytic leukemia) cell lines similar to that of ASP. The antiproliferative response of the ASP-enzymosomes against the Jurkat cells suggests equivalence to that of the free
commercial asparaginase (Aginasa
). Moreover, the ASP-enzymosomes were stable at 4 °C with no significant loss of activity within 4 days and retained 82% activity up to 37 days. Therefore, ASP-enzymosomes are a promising antileukemic drug.
Conflicting findings about the association between leprosy and TLR1 variants N248S and I602S have been reported. Here, we performed case-control and family based studies, followed by replication in 2 ...case-control populations from Brazil, involving 3162 individuals. Results indicated an association between TLR1 248S and leprosy in the case-control study (SS genotype odds ratio OR, 1.81; P = .004) and the family based study (z = 2.02; P = .05). This association was consistently replicated in other populations (combined OR, 1.51; P < .001), corroborating the finding that 248S is a susceptibility factor for leprosy. Additionally, we demonstrated that peripheral blood mononuclear cells (PBMCs) carrying 248S produce a lower tumor necrosis factor/interleukin-10 ratio when stimulated with Mycobacterium leprae but not with lipopolysaccharide or PAM 3 cysK 4 . The same effect was observed after infection of PBMCs with the Moreau strain of bacillus Calmette-Guerin but not after infection with other strains. Finally, molecular dynamics simulations indicated that the Toll-like receptor 1 structure containing 248S amino acid is different from the structure containing 248N. Our results suggest that TLR1 248S is associated with an increased risk for leprosy, consistent with its hypoimmune regulatory function.
•Musculoskeletal symptoms are not the only determinants of chikungunya chronic pain.•Early chikungunya RNA detection in saliva and urine are predictors of chronic pain.•Diarrhea in the acute phase of ...chikungunya infection is associated with chronic pain.
Chikungunya can cause persistent chronic joint pain. Knowledge of the risk factors for disease progression is important for preventing and controlling complications. This study aimed to identify factors associated with chronic joint pain.
This prospective cohort study was conducted at a reference center in Rio de Janeiro. Men and women (aged ≥ 18 years) in the acute phase of Chikungunya were included. Clinical data and samples were collected over three months. Risk factors were evaluated using multivariate and logistic regression analyses.
A total of 107 patients were followed up. The incidence rate of joint tenderness was 61.7 %. Female sex (adjusted odds ratio AOR 3.24, 95 % confidence interval CI:1.07–9.77), diarrhea (AOR 5.08, 95 % CI:1.55–16.67), severe joint pain (AOR 4.26, 95 % CI:1.06–17.06), and CHIKV real-time reverse transcription polymerase chain reaction positivity up to 5 days after the onset of symptoms in urine or saliva (AOR 4.56, 95 % CI:1.41–14.77) were identified as predictors of persistent chronic pain.
In a predominantly female population, musculoskeletal symptoms are not the sole determinant of chronic pain, and careful evaluation of CHIKV detection in alternative body fluids (such as saliva and urine) during the early phase of the disease is warranted.
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