Evaluation of transverse shear stresses in layered beams/plates/shells via stress recovery accounting for various CUF-based theories

This paper exploits the stress recovery technique to evaluate the out-of-plane stress components in the static analysis of composite beams, plates and shells. This technique is implemented in the framework of the Carrera Unified Formulation, an approach allowing the implementation of the theories of structures in a compact way. This work uses Taylor, Legendre and Jacobi polynomials with equivalent single-layer and layer-wise approaches. The finite element method is applied to provide numerical solutions. Multi-layered beams, plates and shells subjected to different loading and boundary conditions are studied to validate and assess the proposed technique. The results are compared with those from the literature and show that the stress recovery technique provides reasonable accuracy for the shear stresses, even with lower-order models. Furthermore, results confirm that, when dealing with thick structures, the adoption of layer-wise models is mandatory to obtain accurate results

Static analysis of thin-walled beams accounting for nonlinearities

This paper presents numerical results concerning the nonlinear analysis of thin-walled isotropic structures via 1D structural theories built with the Carrera Unified Formulation (CUF). Both geometrical and material nonlinearities are accounted for, and square, C- and T-shaped beams are considered. The results focus on equilibrium curves, displacement, and stress distributions. Comparisons with literature and 3D finite elements (FE) are provided to assess the formulation’s accuracy and computational efficiency. It is shown how 1D models based on Lagrange expansions of the displacement field are comparable to 3D FE regarding the accuracy but require considerably fewer degrees of freedom

New Brilliant Blue G Derivative as Pharmacological Tool in Retinal Surgery.

Our study was aimed at assessing the retinal binding of a new synthetic Brilliant Blue G (BBG) derivative (pure benzyl-Brilliant Blue G; PBB) ophthalmic formulation, to improve vitreoretinal surgery procedure. Protein affinity of the new molecule was evaluated in vitro (cell-free assay) and in silico. Furthermore, an ex vivo model of vitreoretinal surgery was developed by using porcine eyes to assess the pharmacological profile of PBB, compared to commercial formulations based on BBG and methyl-BBG (Me-BBG). PBB showed a higher affinity for proteins (p < 0.05), compared to BBG and Me-BBG. In vitro and in silico studies demonstrated that the high selectivity of PBB could be related to high lipophilicity and binding affinity to fibronectin, the main component of the retinal internal limiting membrane (ILM). The PBB staining capabilities were evaluated in porcine eyes in comparison with BBG and Me-BBG. Forty microliters of each formulation were slowly placed over the retinal surface and removed after 30 s. After that, ILM peeling was carried out, and the retina collected. BBG, Me-BBG, and PBB quantification in ILM and retina tissues was carried out by HPLC analysis. PBB levels in the ILM were significantly (p < 0.05) higher compared to BBG and Me-BBG formulations. On the contrary, PBB showed a much lower (p < 0.05) distribution in retina (52 ng/mg tissue) compared to BBG and Me-BBG, in particular PBB levels were significantly (p < 0.05) lower. Therefore, the new synthetic Brilliant Blue derivative (PBB) showed a great ILM selectivity in comparison to underneath retinal layers. In conclusion, these findings had high translational impact with a tangible improving in ex vivo model of retinal surgery, suggesting a future use during surgical practice

Potential uses of olive oil secoiridoids for the prevention and treatment of cancer: A narrative review of preclinical studies

The Mediterranean diet (MD) is a combination of foods mainly rich in antioxidants and anti-inflammatory nutrients that have been shown to have many health-enhancing effects. Extra-virgin olive oil (EVOO) is an important component of the MD. The importance of EVOO can be attributed to phenolic compounds, represented by phenolic alcohols, hydroxytyrosol, and tyrosol, and to secoiridoids, which include oleocanthal, oleacein, oleuropein, and ligstroside (along with the aglycone and glycosidic derivatives of the latter two). Each secoiridoid has been studied and char-acterized, and their effects on human health have been documented by several studies. Secoiridoids have antioxidant, anti-inflammatory, and anti-proliferative properties and, therefore, exhibit anti-cancer activity. This review summarizes the most recent findings regarding the pharmacological properties, molecular targets, and action mechanisms of secoiridoids, focusing attention on their preventive and anti-cancer activities. It provides a critical analysis of preclinical, in vitro and in vivo, studies of these natural bioactive compounds used as agents against various human cancers. The prospects for their possible use in human cancer prevention and treatment is also discussed

Gut-dependent inflammation and alterations of the intestinal microbiota in individuals with perinatal HIV exposure and different HIV serostatus

Objective: HIV-exposed infected (HEI) and uninfected (HEU) children represent the two possible outcomes of maternal HIV infection. Modifications of the intestinal microbiome have been linked to clinical vulnerability in both settings, yet whether HEI and HEU differ in terms of gut impairment and peripheral inflammation/activation is unknown. Design: We performed a cross-sectional, pilot study on fecal and plasma microbiome as well as plasma markers of gut damage, microbial translocation, inflammation and immune activation in HIV-infected and uninfected children born from an HIV-infected mother. Methods: Fecal and plasma microbiome were determined by means of 16S rDNA amplification with subsequent qPCR quantification. Plasma markers were quantified via ELISA. Results: Forty-seven HEI and 33 HEU children were consecutively enrolled. The two groups displayed differences in fecal beta-diversity and relative abundance, yet similar microbiome profiles in plasma as well as comparable gut damage and microbial translocation. In contrast, monocyte activation (sCD14) and systemic inflammation (IL-6) were significantly higher in HEI than HEU. Conclusion: In the setting of perinatal HIV infection, enduring immune activation and inflammation do not appear to be linked to alterations within the gut. Given that markers of activation and inflammation are independent predictors of HIV disease progression, future studies are needed to understand the underlying mechanisms of such processes and elaborate adjuvant therapies to reduce the clinical risk in individuals with perinatal HIV infection

Oleocanthal Exerts Antitumor Effects on Human Liver and Colon Cancer Cells Through ROS Generation

The beneficial health properties of the Mediterranean diet are well recognized. The principle source of fat in Mediterranean diet is extra-virgin olive oil (EVOO). Oleocanthal (OC) is a naturally occurring minor phenolic compound isolated from EVOO, which has shown a potent anti-inflammatory activity, by means of its ability to inhibit the cyclooxygenase (COX) enzymes COX-1 and COX-2. A large body of evidence indicates that phenols exhibit anticancer activities. The aim of the present study was to evaluate the potential anticancer effects of OC in hepatocellular carcinoma (HCC) and colorectal carcinoma (CRC) models. A panel of human HCC (HepG2, Huh7, Hep3B and PLC/PRF/5) and CRC (HT29, SW480) cell lines was used. Cells were treated with OC, and cell viability and apoptosis were evaluated. Compared with classical commercially available COX inhibitors (ibuprofen, indomethacin, nimesulide), OC was more effective in inducing cell growth inhibition in HCC and CRC cells. Moreover, OC inhibited colony for mation and i nduced ap optosis, as confirmed by PARP cleavage, activation of caspases 3/7 and chromatin condensation. OC treatment in a dose dependent-manner induced expression of \uce\ub3H2AX, a marker of DNA damage, increased intracellular ROS production and caused mitochondrial depolarization. Moreover, the effects of OC were suppressed by the ROS scavenger N-acetyl-L-cysteine. Finally, OC was not toxic in primary normal human hepatocytes. In conclusion, OC treatment was found to exert a potent anticancer activity against HCC and CRC cells. Taken together, our findings provide preclinical support of the chemotherapeutic potential of EVOO against cancer

INTEGRAL observations of five sources in the Galactic Center region

A number of new X-ray sources (IGR J17091-3624, IGR/XTE J17391-3021, IGR J17464-3213 (= XTE J17464-3213 = H 1743-322), IGR J17597-2201, SAX/IGR J18027-2017) have been observed with the INTEGRAL observatory during ultra deep exposure of the Galactic Center region in August-September 2003. Most of them were permanently visible by the INTEGRAL at energies higher than $\sim 20$ keV, but IGR/XTE J17391-3021 was observed only during its flaring activity with a flux maximum of $\sim120$ mCrab. IGR J17091-3624, IGR J17464-3213 and IGR J17597-2201 were detected up to $\sim 100$-150 keV. In this paper we present the analysis of INTEGRAL observations of these sources to determine the nature of these objects. We conclude that all of them have a galactic origin. Two sources are black hole candidates (IGR J17091-3624 and IGR J17464-3213), one is an LMXB neutron star binary (presumably an X-ray burster) and two other sources (IGR J17597-2201 and SAX/IGR J18027-2017) are neutron stars in high mass binaries; one of them (SAX/IGR J18027-2017) is an accreting X-ray pulsar.Comment: 8 pages, 7 figures, 2 tables, accepted for publication in A&

Unlocking the Stability of Reduced Graphene Oxide Nanosheets in Biological Media via Use of Sodium Ascorbate

Graphene oxide and reduced graphene oxide (RGO) are carbon bidimensional nanomaterials largely exploited in biomedicine. Their unique interactions with eukaryotic and prokaryotic cells are used to obtain precise intracellular delivery, to create device coatings, and to design theranostic materials for both therapeutic and imaging applications, mainly in the cancer research field. It is known, however, that the hydrophobic behavior of RGO limits its stability in biological media. Here, the employment of sodium ascorbate (NaA) as a reducing agent for the preparation of RGO to provide a nanomaterial with remarkable suitability for applications in cell culture media is proposed. It is demonstrated via a combined experimental and theoretical approach that NaA is able to yield a peculiar RGO derivative, exerting a twofold effect, that is, C sp2 network restoration upon epoxide reduction and RGO edge functionalization via H-bonding, lending RGO a so far unexampled dispersibility in aqueous-based media. The kinetic stability of the bidimensional layers of RGO obtained from NaA is demonstrated together with its superior biocompatibility for drug delivery, unlocking outstanding potentialities for biological applications

In human retinoblastoma Y79 cells okadaic acid\u2013parthenolide co-treatment induces synergistic apoptotic effects, with PTEN as a key player.

Retinoblastoma is the most common intraocular malignancy of childhood. In developing countries, treatment is limited, long-term survival rates are low and current chemotherapy causes significant morbidity to pediatric patients and significantly limits dosing. Therefore there is an urgent need to identify new therapeutic strategies to improve the clinical outcome of patients with retinoblastoma. here, we investigated the effects of two natural compounds okadaic acid (OKa) and parthenolide (PN) on human retinoblastoma Y79 cells. For the first time we showed that OKa/PN combination at subtoxic doses induces potent synergistic apoptotic effects accompanied by lowering in p-akt levels, increasing in the stabilized forms of p53 and potent decrease in ps166-Mdm2. We also showed the key involvement of PTeN which, after OKa/PN treatment, potently increased before p53, thus suggesting that p53 activation was under PTeN action. Moreover, after PTEN-knockdown p-akt/ ps166Mdm2 increased over basal levels and p53 significantly lowered, while OKa/PN treatment failed both to lower p-akt and ps166-Mdm2 and to increase p53 below/over their basal levels respectively. OKa/PN treatment potently increased ROs levels whereas decreased those of Gsh. Reducing cellular Gsh by l-butathionine-[s,R]-sulfoximine treatment significantly anticipated the cytotoxic effect exerted by OKa/ PN. Furthermore, the effects of OKa/PN treatment on both Gsh content and cell viability were less pronounced in PTeN silenced cells than in control cells. The results provide strong suggestion for combining a treatment approach that targets the PTeN/akt/Mdm2/p53 pathway