Leptin Signaling in Obesity and Colorectal Cancer

Obesity and colorectal cancer (CRC) are among the leading diseases causing deaths in the world, showing a complex multifactorial pathology. Obesity is considered a risk factor in CRC development through inflammation, metabolic, and signaling processes. Leptin is one of the most important adipokines related to obesity and an important proinflammatory marker, mainly expressed in adipose tissue, with many genetic variation profiles, many related influencing factors, and various functions that have been ascribed but not yet fully understood and elucidated, the most important ones being related to energy metabolism, as well as endocrine and immune systems. Aberrant signaling and genetic variations of leptin are correlated with obesity and CRC, with the genetic causality showing both inherited and acquired events, in addition to lifestyle and environmental risk factors; these might also be related to specific pathogenic pathways at different time points. Moreover, mutation gain is a crucial factor enabling the genetic process of CRC. Currently, the inconsistent and insufficient data related to leptin’s relationship with obesity and CRC indicate the necessity of further related studies. This review summarizes the current knowledge on leptin genetics and its potential relationship with the main pathogenic pathways of obesity and CRC, in an attempt to understand the molecular mechanisms of these associations, in the context of inconsistent and contradictory data. The understanding of these mechanisms linking obesity and CRC could help to develop novel therapeutic targets and prevention strategies, resulting in a better prognosis and management of these diseases.     

Theranostic Agent Combining Fullerene Nanocrystals and Gold Nanoparticles for Photoacoustic Imaging and Photothermal Therapy

Developing photoactivatable theranostic platforms with integrated functionalities of biocompatibility, targeting, imaging contrast, and therapy is a promising approach for cancer diagnosis and therapy. Here, we report a theranostic agent based on a hybrid nanoparticle comprising fullerene nanocrystals and gold nanoparticles (FGNPs) for photoacoustic imaging and photothermal therapy. Compared to gold nanoparticles and fullerene crystals, FGNPs exhibited stronger photoacoustic signals and photothermal heating characteristics by irradiating light with an optimal wavelength. Our studies demonstrated that FGNPs could kill cancer cells due to their photothermal heating characteristics in vitro. Moreover, FGNPs that are accumulated in tumor tissue via the enhanced permeation and retention effect can visualize tumor tissue due to their photoacoustic signal in tumor xenograft model mice. The theranostic agent with FGNPs shows promise for cancer therapy.     

Targeting CD10 on B-Cell Leukemia Using the Universal CAR T-Cell Platform (UniCAR)

Chimeric antigen receptor (CAR)-expressing T-cells are without a doubt a breakthrough therapy for hematological malignancies. Despite their success, clinical experience has revealed several challenges, which include relapse after targeting single antigens such as CD19 in the case of B-cell acute lymphoblastic leukemia (B-ALL), and the occurrence of side effects that could be severe in some cases. Therefore, it became clear that improved safety approaches, and targeting multiple antigens, should be considered to further improve CAR T-cell therapy for B-ALL. In this paper, we address both issues by investigating the use of CD10 as a therapeutic target for B-ALL with our switchable UniCAR system. The UniCAR platform is a modular platform that depends on the presence of two elements to function. These include UniCAR T-cells and the target modules (TMs), which cross-link the T-cells to their respective targets on tumor cells. The TMs function as keys that control the switchability of UniCAR T-cells. Here, we demonstrate that UniCAR T-cells, armed with anti-CD10 TM, can efficiently kill B-ALL cell lines, as well as patient-derived B-ALL blasts, thereby highlighting the exciting possibility for using CD10 as an emerging therapeutic target for B-cell malignancies.     

Zur Bestimmung der Wasseraufnahmefähigkeit pulverförmiger Proteinrohstoffe 1. Mitt. Die Kapillarsaugmethode

Die Kapillarsaugmethode ermöglicht eine einfache und schnelle Bestimmung der Wasseraufnahmefähigkeit pulverförmiger Proteinrohstoffe. In Untersuchungen an 10 verschiedenen Proteinrohstoffen wird ge-zeigt. daß sich mit zunehmender Einwaage (Schichtdicke) die in g Wasser/g Pulver ausgedrückte Wasseraufnahme leicht erhöht. Bei Einwaagen zwischen 50 und 200 mg ist die Abhängigkeit jedoch so gering, daß sie vernachlässigt werden kann. Mit der Korngröße nimmt die Wasseraufnahme exponentiell zu. Nur bei Korngrößen zwischen 50 und 110 μm Durchmesser kann dies außer acht gelassen werden. Die Art des Proteinrohstoffs, Temperatur, pH-Wert und Ionenmilieu wirken sich unterschiedlich aus. Die Standardabweichung der Methode ist bei Proteinrohstoffen unabhängig von der Größe des Meßwertes und betragt 0,075 g je g Die Bestimmungsgrenze des Verfahrens liegt für eine Einzelbestimmung bei 0,28 und für eine Dreifach-bestimmung bei 0,16 g/g. Die mit der Kapillarsaugmethode verfolgte Wasseraufnahme von Proteinrohstoffen kann nach einer Kinetik nullter (Vorgang mit konstanter Wasseraufnahmerate, z. B. Quellung) oder erster Ordnung (Adsorption) verlaufen, bzw. sie geht in eine gemischte Kinetik über. L. HEINEVFTTER, J. KROLL, B. GASSMANN and K. HOPPE: Determination of the capability of water uptaking by powdery protein raw materials. Part 1. The capillary suction method. The capillary suction method permits simple and rapid determination of the capability of water uptaking by powdery protein raw materials. Investigations with 10 different protein raw materials have demonstrated, that the water uptake expressed in gram water per gram powder is weakly increased, if the amount of sample taken and the layer thickness respectively has been increased. At amounts in the range of 50 to 200 mg however this dependence is insignificantly, so it may be neglected. The water uptake increases exponentially with increasing particle size. Only in case of particle sizes with diameters between 50 and 110 μm this may be ignored. Kind of protein material, temperature, pH value and ion relationships have diverse effects. The Standard deviation of the method related to protein raw materials is independent of the value order measured and amounts 0,075 g/g. The detection limit of the method in case of single determinations is about 0.28 g/g and in case of triple determinations it is 0,16 g/g. The water uptake by protein raw materials followed up with the capillary suction method can be represented by a zero order kinetics (process with constant water uptake rate, i.e. swelling) or by a first order kinetics (water adsorption), otherwise the water uptake rate-may change over to a mixed order kinetics.     

Surface Engineered Carboxymethylchitosan/Poly(amidoamine) Dendrimer Nanoparticles for Intracellular Targeting

Novel highly branched biodegradable macromolecular systems have been developed by grafting carboxymethylchitosan (CMCht) onto low generation poly(amidoamine) (PAMAM) dendrimers. Such structures organize into sphere‐like nanoparticles that are proposed to be used as carriers to deliver bioactive molecules aimed at controlling the behavior of stem cells, namely their proliferation and differentiation. The nanoparticles did not exhibit significant cytotoxicity in the range of concentrations below 1 mg mL^?1, and fluorescent probe labeled nanoparticles were found to be internalized with highly efficiency by both human osteoblast‐like cells and rat bone marrow stromal cells, under fluorescence‐activated cell sorting and fluorescence microscopy analyses. Dexamethasone (Dex) has been incorporated into CMCht/PAMAM dendrimer nanoparticles and release rates were determined by high performance liquid chromatography. Moreover, the biochemical data demonstrates that the Dex‐loaded CMCht/PAMAM dendrimer nanoparticles promote the osteogenic differentiation of rat bone marrow stromal cells, in vitro. The nanoparticles exhibit interesting physicochemical and biological properties and have great potential to be used in fundamental cell biology studies as well as in a variety of biomedical applications, including tissue engineering and regenerative medicine.     

ICI Reduction in OFDM Systems Using Phase Modified Sinc Pulse

This paper is focused on the problem of reducing the intercarrier-interference (ICI) power in the transmission over Orthogonal Frequency Division Multiplexing Systems (OFDM) using pulse shaping methods. A new pulse was proposed here and it was investigated in terms of ICI interference. It appears to be suitable for transmission in OFDM systems with carrier frequency offset. The results obtained by calculations show that the performance improvements are significant for reducing average intercarrier-interference (ICI) power and increasing the ratio of average signal power to average ICI power (SIR).     

Non‐Toxic Dry‐Coated Nanosilver for Plasmonic Biosensors

The plasmonic properties of noble metals facilitate their use for in vivo bio‐applications such as targeted drug delivery and cancer cell therapy. Nanosilver is best suited for such applications as it has the lowest plasmonic losses among all such materials in the UV‐visible spectrum. Its toxicity, however, can destroy surrounding healthy tissues and thus, hinders its safe use. Here, that toxicity against a model biological system (Escherichia coli) is “cured” or blocked by coating nanosilver hermetically with a about 2 nm thin SiO₂ layer in one‐step by a scalable flame aerosol method followed by swirl injection of a silica precursor vapor (hexamethyldisiloxane) without reducing the plasmonic performance of the enclosed or encapsulated silver nanoparticles (20–40 nm in diameter as determined by X‐ray diffraction and microscopy). This creates the opportunity to safely use powerful nanosilver for intracellular bio‐applications. The label‐free biosensing and surface bio‐functionalization of these ready‐to‐use, non‐toxic (benign) Ag nanoparticles is presented by measuring the adsorption of bovine serum albumin (BSA) in a model sensing experiment. Furthermore, the silica coating around nanosilver prevents its agglomeration or flocculation (as determined by thermal annealing, optical absorption spectroscopy and microscopy) and thus, enhances its biosensitivity, including bioimaging as determined by dark field illumination.     

An Adaptable and Scalable Generator of Distributed Massive MIMO Baseband Processing Systems

Journal of Signal Processing Systems - This paper presents an algorithm-adaptable, scalable, and platform-portable generator for massive multiple-input multiple-output (MIMO) baseband processing...