3D printable acrylate polydimethylsiloxane resins for cell culture and drug testing.

Nowadays, most of the microfluidic devices for biological applications are fabricated with only few well-established materials. Among these, polydimethylsiloxane (PDMS) is the most used and known. However, it has many limitations, like the operator dependent and time-consuming manufacturing technique and the high molecule retention.

Nanotechnological engineering of extracellular vesicles for the development of actively targeted hybrid nanodevices.

Background: We propose an efficient method to modify B-cell derived EVs by loading them with a nanotherapeutic stimuli-responsive cargo and equipping them with antibodies for efficient targeting of lymphoma cells.

Results: The post-isolation engineering of the EVs is accomplished by a freeze-thaw method to load therapeutically-active zinc oxide nanocrystals (ZnO NCs), obtaining the so-called TrojanNanoHorse (TNH) to recall the biomimetism and cytotoxic potential of this novel nanoconstruct. TNHs are further modified at their surface with anti-CD20 monoclonal antibodies (TNH) achieving specific targeting against lymphoid cancer cell line.

Smart Shockwave Responsive Titania-Based Nanoparticles for Cancer Treatment.

Nanomedicine is an emerging treatment approach for many cancers, characterized by having high sensitivity and selectivity for tumor cells and minimal toxic effects induced by the conventional chemotherapeutics. In these context, smart nanoparticles (NPs) are getting increasingly relevant in the development of new therapies. NPs with specific chemical composition and/or structure and being stimuli-responsive to magnetic, light or ultrasound waves are new promising tools.

Extracellular Vesicles and Their Current Role in Cancer Immunotherapy.

Extracellular vesicles (EVs) are natural particles formed by the lipid bilayer and released from almost all cell types to the extracellular environment both under physiological conditions and in presence of a disease. EVs are involved in many biological processes including intercellular communication, acting as natural carriers in the transfer of various biomolecules such as DNA, various RNA types, proteins and different phospholipids. Thanks to their transfer and targeting abilities, they can be employed in drug and gene delivery and have been proposed for the treatment of different diseases, including cancer.

The investigation of the parameters affecting the ZnO nanoparticle cytotoxicity behaviour: a tutorial review.

In the last 30 years the research about zinc oxide nanoparticles (ZnO NPs) and their related toxicity has shown a boom. ZnO NPs show cytotoxicity for both prokaryotic and eukaryotic cells and many studies demonstrated their selective toxicity towards cancer cells. However, with the increasing number of publications, it is observed an increase in the discrepancies obtained between the various results.

EVs and Bioengineering: From Cellular Products to Engineered Nanomachines.

Extracellular vesicles (EVs) are natural carriers produced by many different cell types that have a plethora of functions and roles that are still under discovery. This review aims to be a compendium on the current advancement in terms of EV modifications and re-engineering, as well as their potential use in nanomedicine. In particular, the latest advancements on artificial EVs are discussed, with these being the frontier of nanomedicine-based therapeutics.

Zinc Oxide Nanocrystals and High-Energy Shock Waves: A New Synergy for the Treatment of Cancer Cells.

In the last years, different nanotools have been developed to fight cancer cells. They could be administered alone, exploiting their intrinsic toxicity, or remotely activated to achieve cell death. In the latter case, ultrasound (US) has been recently proposed to stimulate some nanomaterials because of the US outstanding property of deep tissue penetration and the possibility of focusing.

ZnO nanocrystals shuttled by extracellular vesicles as effective Trojan nano-horses against cancer cells.

The effective application of nanoparticles in cancer theranostics is jeopardized by their aggregation in biological media, rapid degradation and clearance. The design of biomimetic nanoconstructs with enhanced colloidal stability and non-immunogenicity is therefore essential. We propose naturally stable cell-derived extracellular vesicles to encapsulate zinc oxide (ZnO) nanocrystals as efficacious nanodrugs, to obtain highly biomimetic and stable Trojan nano-horses (TNHs).

Nanoparticle-assisted ultrasound: A special focus on sonodynamic therapy against cancer.

At present, ultrasound radiation is broadly employed in medicine for both diagnostic and therapeutic purposes at various frequencies and intensities. In this review article, we focus on therapeutically-active nanoparticles (NPs) when stimulated by ultrasound. We first introduce the different ultrasound-based therapies with special attention to the techniques involved in the oncological field, then we summarize the different NPs used, ranging from soft materials, like liposomes or micro/nano-bubbles, to metal and metal oxide NPs.

A Microwave-Assisted Synthesis of Zinc Oxide Nanocrystals Finely Tuned for Biological Applications.

Herein we report a novel, easy, fast and reliable microwave-assisted synthesis procedure for the preparation of colloidal zinc oxide nanocrystals (ZnO NCs) optimized for biological applications. ZnO NCs are also prepared by a conventional solvo-thermal approach and the properties of the two families of NCs are compared and discussed. All of the NCs are fully characterized in terms of morphological analysis, crystalline structure, chemical composition and optical properties, both as pristine nanomaterials or after amino-propyl group functionalization.

Enhanced biostability and cellular uptake of zinc oxide nanocrystals shielded with a phospholipid bilayer.

The widespread use of ZnO nanomaterials for biomedical applications, including therapeutic drug delivery or stimuli-responsive activation, as well as imaging, imposes a careful control over the colloidal stability and long-term behaviour of ZnO in biological media. Moreover, the effect of ZnO nanostructures on living cells, in particular cancer cells, is still under debate. This paper discusses the role of surface chemistry and charge of zinc oxide nanocrystals, of around 15 nm in size, which influence their behaviour in biological fluids and effect on cancer cells.

PARP1 expression drives the synergistic antitumor activity of trabectedin and PARP1 inhibitors in sarcoma preclinical models.

Background: Enhancing the antitumor activity of the DNA-damaging drugs is an attractive strategy to improve current treatment options. Trabectedin is an isoquinoline alkylating agent with a peculiar mechanism of action. It binds to minor groove of DNA inducing single- and double-strand-breaks.

Effectiveness of an hospital bed management model: results of four years of follow-up.

Background: Several experiences of Bed Management have been published, most of them focusing on Emergency Department organization. Aosta Hospital is 70 km away from the nearest Hospital, so that ambulance diversion is not feasible and patients' admissions from ED need to be managed at the local level solely. Aim of this study was to test efficacy of an innovative Bed Management model.

Readily Accessible Bulky Iron Catalysts exhibiting Site Selectivity in the Oxidation of Steroidal Substrates.

Bulky iron complexes are described that catalyze the site-selective oxidation of alkyl C-H bonds with hydrogen peroxide under mild conditions. Steric bulk at the iron center is introduced by appending trialkylsilyl groups at the meta-position of the pyridines in tetradentate aminopyridine ligands, and this effect translates into high product yields, an enhanced preferential oxidation of secondary over tertiary C-H bonds, and the ability to perform site-selective oxidation of methylenic sites in terpenoid and steroidal substrates. Unprecedented site selective oxidation at C6 and C12 methylenic sites in steroidal substrates is shown to be governed by the chirality of the catalysts.

Recent Advances in the Selective Oxidation of Alkyl C-H Bonds Catalyzed by Iron Coordination Complexes.

Selective and stereoretentive oxidation of alkyl C-H bonds has been described over the last decade by employing biologically inspired iron coordination complexes as catalysts and hydrogen peroxide as oxidant. Examples of catalyst dependent C-H site selectivity have started to appear. The current paper describes an account of these findings.

The combination of sorafenib and everolimus shows antitumor activity in preclinical models of malignant pleural mesothelioma.

Background: Malignant Pleural Mesothelioma (MPM) is an aggressive tumor arising from mesothelial cells lining the pleural cavities characterized by resistance to standard therapies. Most of the molecular steps responsible for pleural transformation remain unclear; however, several growth factor signaling cascades are known to be altered during MPM onset and progression. Transducers of these pathways, such as PIK3CA-mTOR-AKT, MAPK, and ezrin/radixin/moesin (ERM) could therefore be exploited as possible targets for pharmacological intervention.

Regioselective oxidation of nonactivated alkyl C-H groups using highly structured non-heme iron catalysts.

Selective oxidation of alkyl C-H groups constitutes one of the highest challenges in organic synthesis. In this work, we show that mononuclear iron coordination complexes Λ-[Fe(CF(3)SO(3))(2)((S,S,R)-MCPP)] (Λ-1P), Δ-[Fe(CF(3)SO(3))(2)((R,R,R)-MCPP)] (Δ-1P), Λ-[Fe(CF(3)SO(3))(2)((S,S,R)-BPBPP)] (Λ-2P), and Δ-[Fe(CF(3)SO(3))(2)((R,R,R)-BPBPP)] (Δ-2P) catalyze the fast, efficient, and selective oxidation of nonactivated alkyl C-H groups employing H(2)O(2) as terminal oxidant. These complexes are based on tetradentate N-based ligands and contain iron centers embedded in highly structured coordination sites defined by two bulky 4,5-pinenopyridine donor ligands, a chiral diamine ligand backbone, and chirality at the metal (Λ or Δ).

An iron catalyst for oxidation of alkyl C-H bonds showing enhanced selectivity for methylenic sites.

Many are called but few are chosen: A nonheme iron complex catalyzes the oxidation of alkyl C-H bonds by using H(2)O(2) as the oxidant, showing an enhanced selectivity for secondary over tertiary C-H bonds (see scheme).

Nucleophilic aryl fluorination and aryl halide exchange mediated by a Cu(I)/Cu(III) catalytic cycle.

Copper-catalyzed halide exchange reactions under very mild reaction conditions are described for the first time using a family of model aryl halide substrates. All combinations of halide exchange (I, Br, Cl, F) are observed using catalytic amounts of Cu(I). Strikingly, quantitative fluorination of aryl-X substrates is also achieved catalytically at room temperature, using common F(-) sources, via the intermediacy of aryl-Cu(III)-X species.

Observation and mechanistic study of facile C-O bond formation between a well-defined aryl-copper(III) complex and oxygen nucleophiles.

A well-defined macrocyclic aryl–Cu(III) complex (2) reacts readily with a variety of oxygen nucleophiles, including carboxylic acids, phenols and alcohols, under mild conditions to form the corresponding aryl esters, biaryl ethers and alkyl aryl ethers. The relationship between these reactions and catalytic C-O coupling methods is demonstrated by the reaction of the macrocyclic aryl–Br species with acetic acid and p-fluorophenol in the presence of 10 mol% Cu(I). An aryl-Cu(III)-Br species 2(Br) was observed as an intermediate in the catalytic reaction.

When should asymptomatic patients with combined severe aortic stenosis and aortic insufficiency undergo valve replacement? A clinical case.

Indications to prosthetic aortic valve implantation in patients with aortic stenosis or aortic regurgitation or both stenotic or regurgitant aortic valve, who present without symptoms, are controversial. We present the case of an asymptomatic patient with combined severe aortic stenosis and an equally important insufficiency, undergoing surgery for valve substitution with a bileaflet prosthesis. After surgery he was treated with warfarin according to the doses recommended and underwent follow-up with clinical and echocardiographic exams.

Predictive value of the early response to chemotherapy in high-risk stages II and III Hodgkin's disease.

A series of 60 patients with "high risk" Stage II and III Hodgkin's disease (B symptoms, or large mediastinal mass, or E lung disease) were staged without laparotomy and treated with combined modality treatment: mechlorethamine, vincristine, procarbazine, and prednisone (6 MOPP) plus radiotherapy. Patients were restaged after the first three courses of MOPP and the status of response to therapy at that time was called early response to chemotherapy (ERC). The rate of nitrogen mustard and procarbazine delivery (MRD) during the first three cycles of chemotherapy also was assessed.

Peripheral erythroid precursor and prognosis in chronic granulocytic leukemia.

Seventy-four consecutive patients with nonblastic chronic granulocytic leukemia (CGL) were observed from diagnosis and retrospectively studied. The patients were segregated into three risk groups according to the staging system proposed by Sokal et al. A significant difference in survival was observed only between Stage I and III (P = 0.