Early Osteogenic Marker Expression in hMSCs Cultured onto Acid Etching-Derived Micro- and Nanotopography 3D-Printed Titanium Surfaces

Polyetheretherketone (PEEK) titanium composite (PTC) is a novel interbody fusion device that combines a PEEK core with titanium alloy (Ti6Al4V) endplates. The present study aimed to investigate the in vitro biological reactivity of human bone-marrow-derived mesenchymal stem cells (hBM-MSCs) to micro- and nanotopographies produced by an acid-etching process on the surface of 3D-printed PTC endplates. Optical profilometer and scanning electron microscopy were used to assess the surface roughness and identify the nano-features of etched or unetched PTC endplates, respectively. The viability, morphology and the expression of specific osteogenic markers were examined after 7 days of culture in the seeded cells. Haralick texture analysis was carried out on the unseeded endplates to correlate surface texture features to the biological data. The acid-etching process modified the surface roughness of the 3D-printed PTC endplates, creating micro- and nano-scale structures that significantly contributed to sustaining the viability of hBM-MSCs and triggering the expression of early osteogenic markers, such as alkaline phosphatase activity and bone-ECM protein production. Finally, the topography of 3D-printed PTC endplates influenced Haralick’s features, which in turn correlated with the expression of two osteogenic markers, osteopontin and osteocalcin. Overall, these data demonstrate that the acid-etching process of PTC endplates created a favourable environment for osteogenic differentiation of hBM-MSCs and may potentially have clinical benefit.     

Hypercholesterolemia in Cancer and in Anorexia Nervosa: A Hypothesis for a Crosstalk

The relationship between cholesterol and cancer has been widely demonstrated. Clinical studies have shown changes in blood cholesterol levels in cancer patients. In parallel, basic research studies have shown that cholesterol is involved in the mechanisms of onset and progression of the disease. On the other hand, anorexic patients have high cholesterol levels and a high susceptibility to cancer. In this review, we first present a brief background on the relations among nutrition, eating disorders and cancer. Using several notable examples, we then illustrate the changes in cholesterol in cancer and in anorexia nervosa, providing evidence for their important relationship. Finally, we show a new possible link between cholesterol disorder in cancer and in anorexia nervosa.     

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Ohne Zusammenfassung     

MIL-100(Fe) Sub-Micrometric Capsules as a Dual Drug Delivery System

Nanoparticles of metal–organic frameworks (MOF NPs) are crystalline hybrid micro- or mesoporous nanomaterials that show great promise in biomedicine due to their significant drug loading ability and controlled release. Herein, we develop porous capsules from aggregate of nanoparticles of the iron carboxylate MIL-100(Fe) through a low-temperature spray-drying route. This enables the concomitant one-pot encapsulation of high loading of an antitumor drug, methotrexate, within the pores of the MOF NPs, and the collagenase enzyme (COL), inside the inter-particular mesoporous cavities, upon the formation of the capsule, enhancing tumor treatment. This association provides better control of the release of the active moieties, MTX and collagenase, in simulated body fluid conditions in comparison with the bare MOF NPs. In addition, the loaded MIL-100 capsules present, against the A-375 cancer cell line, selective toxicity nine times higher than for the normal HaCaT cells, suggesting that MTX@COL@MIL-100 capsules may have potential application in the selective treatment of cancer cells. We highlight that an appropriate level of collagenase activity remained after encapsulation using the spray dryer equipment. Therefore, this work describes a novel application of MOF-based capsules as a dual drug delivery system for cancer treatment.     

Polarographische Untersuchungen an 1,3-Thiazinthionen

Polarographic Investigations of 1,3-Thiazinthiones 1,3-Thiazine-6-thiones are stepwise reduced in aprotic media to the corresponding radical anions and dianions. In the case of the 2,4-diphenyl derivative ( 1a ) the radical anion is stable in dimethylformamide, whereas the dianion reacts further to yield the bithiazinylidene ( 4 ) among other products. The effect of substituents on the reduction potentials is discussed.     

The Role of NLRP3 Inflammasome Activation and Oxidative Stress in Varicocele-Mediated Male Hypofertility

Varicocele (VC) is the most common abnormality identified in men evaluated for hypofertility. Increased levels of reactive oxygen species (ROS) and reduced antioxidants concentrations are key contributors in varicocele-mediated hypofertility. Moreover, inflammation and alterations in testicular immunity negatively impact male fertility. In particular, NLRP3 inflammasome activation was hypothesized to lead to seminal inflammation, in which the levels of specific cytokines, such as IL-1β and IL-18, are overexpressed. In this review, we described the role played by oxidative stress (OS), inflammation, and NLRP3 inflammasome activation in VC disease. The consequences of ROS overproduction in testis, including inflammation, lipid peroxidation, mitochondrial dysfunction, chromatin damage, and sperm DNA fragmentation, leading to abnormal testicular function and failed spermatogenesis, were highlighted. Finally, we described some therapeutic antioxidant strategies, with recognized beneficial effects in counteracting OS and inflammation in testes, as possible therapeutic drugs against varicocele-mediated hypofertility.