Editorial: Self-presentation during self quarantine era

[No abstract available

NF-κB activation mechanism of 4-hydroxyhexenal via NIK/IKK and p38 MAPK pathway

Abstract4-Hydroxyhexenal (HHE) is known to affect redox balance during aging, included are vascular dysfunctions. To better understand vascular abnormality through the molecular alterations resulting from HHE accumulation in aging processes, we set out to determine whether up-regulation of mitogen-activated protein kinase (MAPK) by HHE is mediated through nuclear factor kappa B (NF-κB) activation in endothelial cells. HHE induced NF-κB activation by inhibitor of κB (IκB) phosphorylation via the IκB kinase (IKK)/NF-κB inducing kinase (NIK) pathway. HHE increased the activity of p38 MAPK and extracellular signal regulated kinase (ERK), but not c-jun NH2-terminal kinase, indicating that p38 MAPK and ERK are closely involved in HHE-induced NF-κB transactivation. Pretreatment with ERK inhibitor PD98059, and p38 MAPK inhibitor SB203580, attenuated the induction of p65 translocation, IκB phosphorylation, and NF-κB luciferase activity. These findings strongly suggest that HHE induces NF-κB activation through IKK/NIK pathway and/or p38 MAPK and ERK activation associated with oxidative stress in endothelial cells

Pharmacokinetic properties and antitumor efficacy of the 5-fluorouracil loaded PEG-hydrogel

<p>Abstract</p> <p>Background</p> <p>We have studied the <it>in vitro </it>and <it>in vivo </it>utility of polyethylene glycol (PEG)-hydrogels for the development of an anticancer drug 5-fluorouracil (5-FU) delivery system.</p> <p>Methods</p> <p>A 5-FU-loaded PEG-hydrogel was implanted subcutaneously to evaluate the drug retention time and the anticancer effect. For the pharmacokinetic study, two groups of male rats were administered either an aqueous solution of 5-FU (control group)/or a 5-FU-loaded PEG-hydrogel (treated group) at a dose of 100 mg/kg. For the pharmacodynamic study, a human non-small-cell lung adenocarcinoma (NSCLC) cell line, A549 was inoculated to male nude mice with a cell density of 3 × 10⁶. Once tumors start growing, the mice were injected with 5-FU/or 5-FU-loaded PEG-hydrogel once a week for 4 weeks. The growth of the tumors was monitored by measuring the tumor volume and calculating the tumor inhibition rate (IR) over the duration of the study.</p> <p>Results</p> <p>In the pharmacokinetic study, the 5-FU-loaded PEG-hydrogel gave a mean residence time (MRT) of 8.0 h and the elimination half-life of 0.9 h; these values were 14- and 6-fold, respectively, longer than those for the free solution of 5-FU (p < 0.05). In the pharmacodynamic study, A549 tumor growth was significantly inhibited in the 5-FU-loaded PEG-hydrogel group in comparison to the untreated group beginning on Day 14 (p < 0.05-0.01). Moreover, the 5-FU-loaded PEG-hydrogel group had a significantly enhanced tumor IR (p < 0.05) compared to the free 5-FU drug treatment group.</p> <p>Conclusion</p> <p>We suggest that 5-FU-loaded PEG-hydrogels could provide a useful tool for the development of an anticancer drug delivery system.</p

A Novel and Critical Role for Oct4 as a Regulator of the Maternal-Embryonic Transition

Compared to the emerging embryonic stem cell (ESC) gene network, little is known about the dynamic gene network that directs reprogramming in the early embryo. We hypothesized that Oct4, an ESC pluripotency regulator that is also highly expressed at the 1- to 2-cell stages in embryos, may be a critical regulator of the earliest gene network in the embryo.Using antisense morpholino oligonucleotide (MO)-mediated gene knockdown, we show that Oct4 is required for development prior to the blastocyst stage. Specifically, Oct4 has a novel and critical role in regulating genes that encode transcriptional and post-transcriptional regulators as early as the 2-cell stage. Our data suggest that the key function of Oct4 may be to switch the developmental program from one that is predominantly regulated by post-transcriptional control to one that depends on the transcriptional network. Further, we propose to rank candidate genes quantitatively based on the inter-embryo variation in their differential expression in response to Oct4 knockdown. Of over 30 genes analyzed according to this proposed paradigm, Rest and Mta2, both of which have established pluripotency functions in ESCs, were found to be the most tightly regulated by Oct4 at the 2-cell stage.We show that the Oct4-regulated gene set at the 1- to 2-cell stages of early embryo development is large and distinct from its established network in ESCs. Further, our experimental approach can be applied to dissect the gene regulatory network of Oct4 and other pluripotency regulators to deconstruct the dynamic developmental program in the early embryo

Cancer is a Preventable Disease that Requires Major Lifestyle Changes

This year, more than 1 million Americans and more than 10 million people worldwide are expected to be diagnosed with cancer, a disease commonly believed to be preventable. Only 5–10% of all cancer cases can be attributed to genetic defects, whereas the remaining 90–95% have their roots in the environment and lifestyle. The lifestyle factors include cigarette smoking, diet (fried foods, red meat), alcohol, sun exposure, environmental pollutants, infections, stress, obesity, and physical inactivity. The evidence indicates that of all cancer-related deaths, almost 25–30% are due to tobacco, as many as 30–35% are linked to diet, about 15–20% are due to infections, and the remaining percentage are due to other factors like radiation, stress, physical activity, environmental pollutants etc. Therefore, cancer prevention requires smoking cessation, increased ingestion of fruits and vegetables, moderate use of alcohol, caloric restriction, exercise, avoidance of direct exposure to sunlight, minimal meat consumption, use of whole grains, use of vaccinations, and regular check-ups. In this review, we present evidence that inflammation is the link between the agents/factors that cause cancer and the agents that prevent it. In addition, we provide evidence that cancer is a preventable disease that requires major lifestyle changes

Il desiderio di architettura. Quattro progetti di Luciano Semerani e Gigetta Tamaro

La tesi analizza quattro progetti di architettura degli architetti Luciano Semerani e Gigetta Tamaro. I progetti sono: la casa Semerani vicino al borgo di Conconello sulle colline a nord di Trieste, il nuovo Ospedale civile di Trieste a Cattinara, l’Ospedale SS Giovanni e Paolo a Venezia e il progetto per il nuovo Cimitero di Pesaro. Per ognuno di questi progetti sono state individuate le tecniche compositive poste alla base dell’invenzione architettonica. Le analisi compositive sono state sviluppate attraverso disegni planimetrici, ricostruzione geometriche e tridimensionali delle forme dei progetti e tramite modelli di studio. Mediante la ricostruzione grafica dei temi compositivi la tesi ha individuato, seguendo il concetto di desiderio, le estensioni figurative, metaforiche e simboliche rinvenibili nei quattro progetti oggetto di studio. In questo modo sia le tecniche compositive sia i principi teorici posti alla base dell’invenzione progettuale restituiscono un lavoro progettuale in cui gli aspetti della necessità delle opere di architettura si combina con il desiderio e le aspirazioni umane di costruire e abitare un mondo migliore

Dialettica in stato di quiete. Progetto per il nuovo cimitero di Pesaro di Luciano Semerani e Gigetta Tamaro.

This essay proposes an interpretation of the project for a new Pesaro cemetery developed by Luciano Semerani and Gigetta Tamaro in 1979. The fundamental reason why it is considered important to reflect on this unrealized project lies in the exemplary way in which the two architects conceived and developed the project’s forms, pursuing an analogy between those of the “city of the living” and those of the “city of the dead”. This analogy defines the project’s metahistorical space, favouring, in other words, the conception of a symbolic space to which the political task of passing on the common learning on death is entrusted to the life of the city, while each individual is guaranteed a spiritual request which allows him or her to keep a dialogue with the deceased alive.Il testo propone una lettura del progetto per il nuovo cimitero di Pesaro elaborato da Luciano Semerani e Gigetta Tamaro nel 1979. La ragione fondamentale per cui si ritiene rilevante riflettere su questo progetto non realizzato risiede nel modo esemplare con cui i due architetti hanno concepito e sviluppato le forme del progetto rincorrendo all’analogia tra le forme della «città dei vivi» e le forme della «città dei morti». Questa analogia definisce lo spazio metastorico del progetto, favorendo, in altri termini, l’ideazione di uno spazio simbolico a cui è affidato da una parte il compito politico di tramandare nella vita della città l’apprendimento comune della morte e da un’altra parte è garantito ad ogni individuo l’istanza spirituale che consente di tenere vivo il dialogo coi defunti

Diet alters probiotic L actobacillus persistence and function in the intestine

International audienc

Macroscopic Arrays of Block Copolymers with Areal Densities of 10 Terbit/inch2 and Beyond

BCP self-assemble into a range of highly-ordered morphologies and by controlling the orientation and lateral ordering of the nanoscopic microdomains, numerous applications will emerge. By combining the “bottom-up” self-assembly of BCPs with “top-down” micro-fabrication processes faster, better and cheaper devices can be generated in very simple, yet robust, ways. By combining confinement effects with the highly directional field inherent in solvent evaporation and the mobility imparted to the BCP by the solvent, perfectly registered arrays of hexagonally packed BCP microdomains can be produced on surfaces at least 3x3 cm2 in area with areal densities in excess of 10 terabit/inch2. Registry of the arrays and the perfection of the ordering over macroscopic distances were demonstrated by grazing incidence small angle x-ray scattering and scanning force microscopy. Highly aligned and oriented line patterns based on BCP are also of interest, since they overcome a size limitation facing current lithographic technique. However, due to structural imperfections of BCP such as grain boundaries, dislocations, or disclinations, it has been thought that it is difficult to get the well-defined line patterns with high degree of straightness on conventional substrate. Using a saw tooth patterned substrate, a significant enhancement of degree of straightness in line patterns was obtained. However, the line patterns orient normal to the facets on the surface