Is Melanoma Progression Affected by Thyroid Diseases?

Clinical and epidemiological evidence indicate a relationship between thyroid diseases and melanoma. In particular, the hypothyroidism condition appears to promote melanoma spread, which suggests a protective role of thyroid hormones against disease progression. In addition, experimental data suggest that, in addition to thyroid hormones, other hormonal players of the hypothalamic–pituitary–thyroid (HPT) axis, namely the thyrotropin releasing hormone and the thyrotropin, are likely to affect melanoma cells behavior. This information warrants further clinical and experimental studies in order to build a precise pattern of action of the HPT hormones on melanoma cells. An improved knowledge of the involved molecular mechanism(s) could lead to a better and possibly personalized clinical management of these patients.     

The Flavonol Quercitrin Hinders GSK3 Activity and Potentiates the Wnt/β-Catenin Signaling Pathway

The Wnt/β-catenin signaling pathway dictates cell proliferation and differentiation during embryonic development and tissue homeostasis. Its deregulation is associated with many pathological conditions, including neurodegenerative disease, frequently downregulated. The lack of efficient treatment for these diseases, including Alzheimer’s disease (AD), makes Wnt signaling an attractive target for therapies. Interestingly, novel Wnt signaling activating compounds are less frequently described than inhibitors, turning the quest for novel positive modulators even more appealing. In that sense, natural compounds are an outstanding source of potential drug leads. Here, we combine different experimental models, cell-based approaches, neuronal culture assays, and rodent behavior tests with Xenopus laevis phenotypic analysis to characterize quercitrin, a natural compound, as a novel Wnt signaling potentiator. We find that quercitrin potentiates the signaling in a concentration-dependent manner and increases the occurrence of the Xenopus secondary axis phenotype mediated by Xwnt8 injection. Using a GSK3 biosensor, we describe that quercitrin impairs GSK3 activity and increases phosphorylated GSK3β S9 levels. Treatment with XAV939, an inhibitor downstream of GSK3, impairs the quercitrin-mediated effect. Next, we show that quercitrin potentiates the Wnt3a-synaptogenic effect in hippocampal neurons in culture, which is blocked by XAV939. Quercitrin treatment also rescues the hippocampal synapse loss induced by intracerebroventricular injection of amyloid-β oligomers (AβO) in mice. Finally, quercitrin rescues AβO-mediated memory impairment, which is prevented by XAV939. Thus, our study uncovers a novel function for quercitrin as a Wnt/β-catenin signaling potentiator, describes its mechanism of action, and opens new avenues for AD treatments.     

Assessing T-Cell Immunity in Kidney Transplant Recipients with Absent Antibody Production after a 3rd Dose of the mRNA-1273 Vaccine

The vulnerable population of kidney transplant recipients (KTRs) are low responders to COVID-19 vaccines, so specific immune surveillance is needed. The interferon-gamma (IFN-γ) release assay (IGRA) is effective in assessing T cell-mediated immunity. We assessed SARS-CoV-2-directed T cell responses in KTRs with absent antibody production after a third dose of the mRNA-1273 vaccine, using two different IGRAs. A cohort of 57 KTRs, who were actively followed up, received a third dose of the mRNA-1273 vaccine. After the evaluation of humoral immunity to SARS-CoV-2, 14 seronegative patients were tested with two commercial IGRAs (SD Biosensor and Euroimmun). Out of 14 patients, one and three samples were positive by IGRAs with Euroimmun and SD Biosensor, respectively. The overall agreement between the two assays was 85.7% (κ = 0.444). In addition, multivariate linear regression analysis showed no statistically significant association between the IFN-γ concentration, and the independent variables analyzed (age, gender, years since transplant, total lymphocytes cells/mcl, CD3+ cells/mcl, CD3+ CD4+ cells/mcl, CD3+ CD8+ cells/mcl, CD19+ cells/mcl, CD3-CD16+CD56+ cells/mcl) (p > 0.01). In a vulnerable setting, assessing cellular immune response to complement the humoral response may be advantageous. Since the two commercial IGRAs showed a good agreement on negative samples, the three discordant samples highlight the need for further investigations.     

Evolution and resolution of long-term cardiac memory

BACKGROUND: Cardiac memory (CM) refers to T-wave changes induced by ventricular pacing or arrhythmia that accumulate in magnitude and duration with repeated episodes of abnormal activation. We report herein the kinetics of long-term CM and its association with the ventricular action potential. METHODS AND RESULTS: Dogs were paced from the ventricles at rates of 110 to 120 bpm for approximately 3 weeks. CM characterized by gradual sinus rhythm T vector rotation toward the paced QRS vector evolved in all dogs regardless of pacing site (left ventricular [LV] anterior apex or base, posterior LV, or right ventricular free wall). Cardiac hemodynamics and myocardial flow (microsphere studies) were unaltered by the pacing. Recovery time for the memory T wave to return to control increased with duration of the previous pacing. The protein synthesis inhibitor cycloheximide markedly (P<.05) and reproducibly attenuated evolution of CM. When pacing was performed from the atrium, CM did not occur. Standard microelectrode techniques were used to study action potential from the LV free wall of control and CM dogs. CM was associated with increased action potential duration in epicardial and endocardial but not midmyocardial cells, significantly altering the transmyocardial gradient for repolarization. CONCLUSIONS: CM is a dynamic process for which the final T vector is predicted by the paced QRS vector and which is associated with significant changes in epicardial and endocardial but not midmyocardial cell action potential duration, such that the transmural gradient of repolarization is altered. It is unaccompanied by evidence of altered hemodynamics or flow, requires a change in pathway of activation, and appears to require new protein synthesis.     

A double flow cytometric tag allows tracking of the dynamics of cell cycle progression of newborn Saccharomyces cerevisiae cells during balanced exponential growth

Studies on the dynamics of growth of single eukaryotic cells and their relationships with cell cycle regulations are generally carried out following cell synchronization procedures or, on a relatively low number of cells, by time-lapse studies. Establishment of both time-lapse studies and synchronous cell populations usually requires elaborate experimental efforts and is prone to perturb the physiological state of the cell. In this paper we use a new flow cytometric approach which allows, in asynchronous growing Saccharomyces cerevisiae populations, tagging of both the cell age and the cell protein content of a cohort of daughter cells at the different cell cycle set points. Since the cell protein content is a good estimation of the cell size, it is possible to follow the kinetics of the cell size increase during cell cycle progression. The experimental findings obtained indicate an exponential increase of the cell size during growth, that the daughter and the parent subpopulations grow with the same specific growth rate, that the average cell size increase rate of each individual cell is almost identical to the specific growth rate of the overall population and provide the opportunity to estimate the cell cycle length for the daughter cell population as well as the identification of the complex structure of asynchronously growing yeast populations.     

Computed microtomography evaluation of calcium hydroxide‐based root canal dressing removal from oval root canals by different methods of irrigation

The aim of this study was to evaluate the capacity of conventional irrigation, passive ultrasonic irrigation (PUI), and Easy Clean for removing calcium hydroxide‐based root canal dressing from oval root canals. Thirty mandibular uniradicular incisors with oval canals were used, and subjected to chemical–mechanical preparation with Reciproc R40 instruments. The main canal was filled with a paste based on Ca(OH)₂ P.A., iodoform and propylene glycol in the ratio of 3:1:1. The teeth were stored in 100% humidity at a temperature of 37°C for 14 days. Afterwards, the teeth were divided into three groups (n = 10) according to the method of irrigation used (conventional irrigation, PUI, and Easy Clean). The specimens were analyzed by computed microtomography at three time intervals: before placing the root canal dressing, with the root canal dressing in place, and after application of the irrigation methods for removing it. The data were submitted to Kruskal–Wallis and Dunn tests for analyzing the canal as a whole, and Friedman and Dunn for analyzing the root thirds. The results showed that conventional irrigation was less efficient for removing the root canal dressing in comparison with the methods that agitated the irrigant solution (p < .05). When the root canal was analyzed as a whole, Easy Clean, and PUI were similar (p > .05). In analysis of the thirds, Easy Clean was more efficient than conventional irrigation in all the thirds, while PUI showed this behavior only in the cervical third (p < .05). The authors concluded that in oval canals, none of the irrigation methods were capable of removing all the root canal dressing, however, the methods that agitated the irrigant solution were more efficient than conventional irrigation.     

Development and application starch films: PBAT with additives for evaluating the shelf life of Tommy Atkins mango in the fresh-cut state

In this study, formulations of cassava starch and poly(butylene adipate-co-terephthalate) flexible films were developed, with glycerol, coconut nanocellulose, annatto, and citric acid in different concentrations, as well as the effectiveness of the selected materials in fresh-cut mangoes storage was evaluated. The tensile strength of the different formulations varied from 1.90 (E4) to 6.65 MPa (E3c), and the strain varied from 206.31 (E1c) to 278.41% (E8); this variation was dependent on the percentage of the polymer matrix incorporated. The a_w values of the formulations ranged from 0.396 (E2) to 0.569 (E3c). The Formulations E4 and E7 (with additives) presented good properties and were selected to condition mangoes. The micrographs of these films showed regions of micropores that can facilitate the diffusion of water from the packaged product to the surface, allowing decreases in moisture and a_w, which is associated with higher color maintenance during fruit storage. E7 presented better barrier properties than E4 (lower values of WVP and water solubility) which may have influenced in a positive way to maintain the stability of the package in the studied period. E7 can be considered as a viable alternative for minimally processed mango storage. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 48150.     

Hybrid Photonic Nanostructures by In Vivo Incorporation of an Organic Fluorophore into Diatom Algae

Biotechnological processes harnessing living organisms' metabolism are low‐cost routes to nanostructured materials for applications in photonics, electronics, and nanomedicine. In the pursuit of photonic biohybrids, diatoms microalgae are attractive given the properties of the porous micro‐to‐nanoscale structures of the biosilica shells (frustules) they produce. The investigations have focused on in vivo incorporation of tailored molecular fluorophores into the frustules of Thalassiosira weissflogii diatoms, using a procedure that paves the way for easy biotechnological production of photonic nanostructures. The procedure ensures uniform staining of shells in the treated culture and permits the resulting biohybrid photonic nanostructures to be isolated with no damage to the dye and periodic biosilica network. Significantly, this approach ensures that light emission from the dye embedded in the isolated biohybrid silica is modulated by the silica's nanostructure, whereas no modulation of photoluminescence is observed upon grafting the fluorophore onto frustules by an in vitro approach based on surface chemistry. These results pave the way to the possibility of easy production of photonic nanostructures with tunable properties by simple feeding the diatoms algae with tailored photoactive molecules.