In order to understand how omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplements affect breast cancer prevention and treatment, a systematic review of articles published in the last 5 years in ...two databases was performed. Of the 679 articles identified, only 27 were included and examined based on five topics, taking into account: the induction type of the breast cancer used in animal models; the characteristics of the induction model by cell transplantation; the experimental design of the ω-3 supplementation-combined or not with a treatment antitumor drug; the fatty acids (FAs) composition used; the analysis of the studies' outcomes. There are diverse and well-established animal models of breast cancer in the literature, with very relevant histological and molecular similarities depending on the specific objective of the study, such as whether the method of tumor induction was transgenic, by cell transplantation, or by oncogenic drugs. The analyses of outcomes were mainly focused on monitoring tumor growth, body/tumor weight, and molecular, genetic, or histological analyses, and few studies evaluated latency, survival, or metastases. The best results occurred when supplementation with ω-3 PUFA was associated with antitumor drugs, especially in the analysis of metastases and volume/weight of tumors or when the supplementation was started early and maintained for a long time. However, the beneficial effect of ω-3 PUFA supplementation when not associated with an antitumor agent remains unclear.
Bone marrow transplantation is a treatment for a variety of hematological and non-hematological diseases. For the transplant success, it is mandatory to have a thriving engraftment of transplanted ...cells, which directly depends on their homing. The present study proposes an alternative method to evaluate the homing and engraftment of hematopoietic stem cells using bioluminescence imaging and inductively coupled plasma mass spectrometry (ICP-MS) associated with superparamagnetic iron oxide nanoparticles. We have identified an enriched population of hematopoietic stem cells in the bone marrow following the administration of Fluorouracil (5-FU). Lately, the cell labeling with nanoparticles displayed the greatest internalization status when treated with 30 µg Fe/mL. The quantification by ICP-MS evaluate the stem cells homing by identifying 3.95 ± 0.37 µg Fe/mL in the control and 6.61 ± 0.84 µg Fe/mL in the bone marrow of transplanted animals. In addition, 2.14 ± 0.66 mg Fe/g in the spleen of the control group and 2.17 ± 0.59 mg Fe/g in the spleen of the experimental group was also measured. Moreover, the bioluminescence imaging provided the follow up on the hematopoietic stem cells behavior by monitoring their distribution by the bioluminescence signal. Lastly, the blood count enabled the monitoring of animal hematopoietic reconstitution and ensured the transplantation effectiveness.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Flow cytometry has emerged as a promising technique for detection of SARS‐CoV‐2 antibodies. In this study, we developed an innovative strategy for simultaneous detection of immunoglobulin G (IgG), ...IgM and IgA. The SARS‐CoV‐2 nucleocapsid protein was covalently bound to functional beads surface applying sulpho‐SMCC chemistry. BUV395 anti‐IgG, BB515 anti‐IgM, biotinylated anti‐IgA1/IgA2 and BV421 streptavidin were used as fluorophore conjugated secondary antibodies. Serum and antibodies reaction conditions were optimized for each antibody isotype detection and a multiplexed detection assay was developed. This new cell‐free assay efficiently discriminate COVID‐19 negative and positive samples. The simultaneous detection of IgG, IgM and IgA showed a sensitivity of 88·5–96·2% and specificity of 100%. This novel strategy opens a new avenue for flow cytometry‐based diagnosis.
Significance and Impact of the Study: Flow cytometry has emerged as a promising technique for detection of anti‐SARS‐CoV‐2 antibodies. In this study, we developed an innovative strategy for simultaneous detection of immunoglobulin G (IgG), IgM and IgA. This new cell‐free assay efficiently discriminate COVID‐19 negative and positive samples. The simultaneous detection of IgG, IgM and IgA showed a high sensitivity and specificity. This novel strategy opens a new avenue for flow cytometry‐based diagnosis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Although rare, CALM/AF10 is a chromosomal rearrangement found in immature T-cell acute lymphoblastic leukemia (T-ALL), acute myeloid leukemia, and mixed phenotype acute leukemia of T/myeloid lineages ...with poor prognosis. Moreover, this translocation is detected in 50% of T-ALL patients with gamma/delta T cell receptor rearrangement, frequently associated with low expression of transcription factor CCAAT/enhancer-binding protein alpha (CEBPA). However, the relevance of CEBPA low expression for CALM/AF10 leukemogenesis has not yet been evaluated. We generated double mutant mice, which express the Lck-CALM/AF10 fusion gene and are haploinsufficient for the Cebpa gene. To characterize the hematopoiesis, we quantified hematopoietic stem cells, myeloid progenitor cells, megakaryocyte-erythrocyte progenitor cells, common myeloid progenitor cells, and granulocyte-macrophage progenitor cells. No significant difference was detected in any of the progenitor subsets. Finally, we tested if Cebpa haploinsufficiency would lead to the expansion of Mac-1+/B220+/c-Kit+ cells proposed as the CALM/AF10 leukemic progenitor. Less than 1% of bone marrow cells expressed Mac-1, B220, and c-Kit with no significant difference between groups. Our results showed that the reduction of Cebpa gene expression in Lck-CALM/AF10 mice did not affect their hematopoiesis or induce leukemia. Our data corroborated previous studies suggesting that the CALM/AF10 leukemia-initiating cells are early progenitors with lymphoid/myeloid differentiating potential.
Serum uric acid (sUA) control is of key relevance in tumor lysis syndrome (TLS) prevention as it correlates with both TLS and renal event risk. We sought to determine whether febuxostat fixed dose ...achieves a better sUA control than allopurinol while preserving renal function in TLS prevention.
Patients with hematologic malignancies at intermediate to high TLS risk grade were randomized to receive febuxostat or allopurinol, starting 2 days before induction chemotherapy, for 7–9 days. Study treatment was blinded, whereas daily dose (low/standard/high containing allopurinol 200/300/600 mg, respectively, or fixed febuxostat 120 mg) depended on the investigator's choice. The co-primary end points, sUA area under curve (AUC sUA1–8) and serum creatinine change, were assessed from baseline to day 8 and analyzed through analysis of covariance with two-sided overall significance level of 5%. Secondary end points included treatment responder rate, laboratory and clinical TLS incidence and safety.
A total of 346 patients (82.1% intermediate TLS risk; 82.7% assigned to standard dose) were randomized. Mean AUC sUA1–8 was 514.0±225.71 versus 708.0±234.42 mgxh/dl (P < 0.0001) in favor of febuxostat. Mean serum creatinine change was -0.83 ± 26.98% and -4.92 ± 16.70% for febuxostat and allopurinol, respectively (P = 0.0903). No differences among secondary efficacy end points were detected. Drug-related adverse events occurred in 6.4% of patients in both arms.
In the largest adult trial carried out in TLS prevention, febuxostat achieved a significant superior sUA control with one fixed dose in comparison to allopurinol with comparable renal function preservation and safety profile.
NCT01724528.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This systematic review aimed to verify the use of microfluidic devices in the process of implementing and evaluating the effectiveness of therapeutic approaches in glioblastoma on-a-chip, providing a ...broad view of advances to date in the use of this technology and their perspectives. We searched studies with the variations of the keywords "Glioblastoma", "microfluidic devices", "organ-on-a-chip" and "therapy" of the last ten years in PubMed and Scopus databases. Of 446 articles identified, only 22 articles were selected for analysis according to the inclusion and exclusion criteria. The microfluidic devices were mainly produced by soft lithography technology, using the PDMS material (72%). In the microenvironment, the main extracellular matrix used was collagen type I. Most studies used U87-MG glioblastoma cells from humans and 31.8% were co-cultivated with HUVEC, hCMEC/D3, and astrocytes. Chemotherapy was the majority of therapeutic approaches, assessing mainly the cellular viability and proliferation. Furthermore, some alternative therapies were reported in a few studies (22.6%). This study identified a diversity of glioblastoma on-a-chip to assess therapeutic approaches, often using intermediate levels of complexity. The most advanced level implemented the intersection between different biological systems (liver-brain or intestine-liver-brain), BBB model, allowing in vitro studies with greater human genetic similarity, reproducibility, and low cost, in a highly customizable platform.
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Nicotinic partial agonists provide an accepted aid for smoking cessation and thus contribute to decreasing tobacco-related disease. Improved drugs constitute a continued area of study. However, there ...remains no reductionist method to examine the cellular and subcellular pharmacokinetic properties of these compounds in living cells. Here, we developed new intensity-based drug-sensing fluorescent reporters (iDrugSnFRs) for the nicotinic partial agonists dianicline, cytisine, and two cytisine derivatives - 10-fluorocytisine and 9-bromo-10-ethylcytisine. We report the first atomic-scale structures of liganded periplasmic binding protein-based biosensors, accelerating development of iDrugSnFRs and also explaining the activation mechanism. The nicotinic iDrugSnFRs detect their drug partners in solution, as well as at the plasma membrane (PM) and in the endoplasmic reticulum (ER) of cell lines and mouse hippocampal neurons. At the PM, the speed of solution changes limits the growth and decay rates of the fluorescence response in almost all cases. In contrast, we found that rates of membrane crossing differ among these nicotinic drugs by >30-fold. The new nicotinic iDrugSnFRs provide insight into the real-time pharmacokinetic properties of nicotinic agonists and provide a methodology whereby iDrugSnFRs can inform both pharmaceutical neuroscience and addiction neuroscience.
This study evaluated the influence of ceramic thickness and ceramic materials on fracture resistance of posterior partial coverage ceramic restorations. Forty extracted molars were allocated into ...four groups (n=10) to test for two variables: 1) the thickness of ceramic (1 mm or 2 mm) and 2) the ceramic materials (a lithium disilicate glass-ceramic IPS e.max or leucite-reinforced glass ceramic IPS Empress). All ceramic restorations were luted with resin cement (Variolink II) on the prepared teeth. These luted specimens were loaded to failure in a universal testing machine, in the compression mode, with a crosshead speed of 1.0 mm/min. The data were analyzed using two-way analysis of variance and the Tukey Honestly Significantly Different multiple comparison test (α =0.05). The fracture resistance revealed a significant effect for materials (p<0.001); however, the thickness of ceramic was not significant (p=0.074), and the interaction between the thickness of ceramic and the materials was not significant (p=0.406). Mean (standard deviation) fracture resistance values were as follows: a 2-mm thickness of a lithium disilicate bonded to tooth structure (2505 401 N) revealed a significantly higher fracture resistance than did a 1-mm thickness of leucite-reinforced (1569 452 N) and a 2-mm thickness of leucite-reinforced ceramic bonded to tooth structure (1716 436 N) (p<0.05). There was no significant difference in fracture resistance values between a lithium disilicate ceramic at 1-mm thickness (2105 567 N) and at 2-mm thickness. Using a lithium disilicate glass ceramic for partial coverage restoration significantly improved fracture resistance compared to using a leucite-reinforced glass ceramic. The thickness of ceramic had no significant effect on fracture resistance when the ceramics were bonded to the underlying tooth structure.
HIV has become increasingly prevalent in the Northeast region of Brazil where
Leishmania infantum chagasi is endemic, and concurrent AIDS and visceral leishmaniasis (VL) has emerged. In this study, ...persons with HIV/AIDS and VL (
n
=
17) had a mean age of 37.3 years (range 29–53 years) compared with 12.5 years (1–80 years) for persons with VL alone (
n
=
2836). Males accounted for 88% of cases with concurrent VL and AIDS and 65% of those with VL alone. The mean CD4 count and antileishmanial antibody titre were lower and recurrence of VL and death were more likely with co-infection. Considering the prevalences of
L.i. chagasi and HIV in the region, this may herald the emergence of an important public health problem.
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