Regulatory aspects of a nanomaterial for imaging therapeutic cells.

The ability to track therapeutic cells upon administration to the patient is of interest to both regulators and developers of cell therapy. The European Commission Horizon2020 project nTRACK from 2017-2022 aimed to develop a multi-modal nano-imaging agent to track therapeutic cells during development of a cell therapy. As part of this project, we investigated the regulatory pathway involved for such a product if marketed as a stand-alone product.

The Osteogenesis Mechanisms of Dental Alveolar Bone Socket Post Induction with Hydroxyapatite Bovine Tooth Graft: An Animal Experimental in Rattus norvegicus Strain Wistar.

Objectives:  Surgical endodontics (hemisection) commonly involves the alveolar bone socket and the periradicular tissue. In today's era, optimizing the bone healing process is updated by using bone graft induction. This study explores the mechanisms of bone healing of the alveolar bone socket post-dental extraction of Wistar rats after administration of a bovine tooth graft (hydroxyapatite bovine tooth graft [-BTG]).

Urine metabolomic analysis for monitoring internal load in professional football players.

Introduction: The design of training programs for football players is not straightforward due to intra- and inter-individual variability that leads to different physiological responses under similar training loads.

Objective: To study the association between the external load, defined by variables obtained using electronic performance tracking systems (EPTS), and the urinary metabolome as a surrogate of the metabolic adaptation to training.

Methods: Urine metabolic and EPTS data from 80 professional football players collected in an observational longitudinal study were analyzed by ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry and assessed by partial least squares (PLS) regression.

Rationale and design of the FELICITAR registry (Frailty Evaluation After List Inclusion, Characteristics and Influence on Transplantation and Results).

Frailty reflects a state of decreased physiological reserve and vulnerability to stressors. Its prevalence among patients with cardiovascular disease is as high as 60%. Frailty is associated with a poor prognosis for patients with heart failure, increasingly frequent hospitalization, and death.

S100A7: from mechanism to cancer therapy.

Within the tumor, malignant and stromal cells support each other by secreting a wide variety of growth factors and cytokines, allowing tumor growth and disease progression. The identification and regulation of those key factors in this crosstalk has opened the opportunity to develop new therapeutic strategies that not only act on the tumor cells but also on the stroma. Among these factors, S100A7 protein has gained interest in the last years.

Cellular Uptake and Cytotoxic Effect of Epidermal Growth Factor Receptor Targeted and Plitidepsin Loaded Co-Polymeric Polymersomes on Colorectal Cancer Cell Lines.

Encapsulating chemotherapy drugs in targeted nanodelivery systems is one of the most promising approaches to tackle cancer disease, avoiding side effects of common treatment. In the last decade, several nanocarriers with different nature have been tested, but polypeptide-based copolymers have attracted considerable attention for their biocompatibility, controlled and slow biodegradability as well as their low toxicity. In this work, we synthesized, characterized and evaluated poly(trimethylene carbonate)-bock-poly(L-glutamic acid) derived polymersomes, targeted to epidermal growth factor receptor (EGFR), loaded with plitidepsin and ultimately tested in HT29 and LS174T colorectal cancer cell lines for specificity and efficacy.

Surface decorated poly(ester-ether-urethane)s nanoparticles: a versatile approach towards clinical translation.

Poly(ester-ether-urethane)s copolymers are a resourceful class of biopolymers for the preparation of nanocarriers for drug delivery applications. However, a simple clinical translation for this synthetic material with biological and quality features is still needed. In this view, poly(ε-caprolactone)-co-poly(ethylene glycol) copolymers were synthesized as semi-bulk pilot (Kg) scale under mild conditions in absence of catalyst, bearing functional termini such as fluorescein tag and anticancer targeting moieties.

In vivo anticancer evaluation of the hyperthermic efficacy of anti-human epidermal growth factor receptor-targeted PEG-based nanocarrier containing magnetic nanoparticles.

Polymeric nanoparticles with targeting moieties containing magnetic nanoparticles as theranostic agents have considerable potential for the treatment of cancer. Here we report the chemical synthesis and characterization of a poly(D,L-lactide-co-glycolide)-b-poly(ethylene glycol)-based nanocarrier containing iron oxide nanoparticles and human epithelial growth factor receptor on the outer shell. The nanocarrier was also radiolabeled with (99m)Tc and tested as a theranostic nanomedicine, ie, it was investigated for both its diagnostic ability in vivo and its therapeutic hyperthermic effects in a standard A431 human tumor cell line.

S100P antibody-mediated therapy as a new promising strategy for the treatment of pancreatic cancer.

Despite progresses in diagnosis and treatment, pancreatic cancer continues to have the worst prognosis of all solid malignant tumors. Recent evidences suggest that the metastasis-promoting protein S100P stimulates pancreatic tumor proliferation, survival, invasion and metastasis progression through extracellular functions. Moreover, its expression is strongly correlated with poor prognosis in patients with several types of cancer although the entire molecular mechanism responsible for the diverse biological functions is not fully understood.

Therapeutic targeting of tumor growth and angiogenesis with a novel anti-S100A4 monoclonal antibody.

S100A4, a member of the S100 calcium-binding protein family secreted by tumor and stromal cells, supports tumorigenesis by stimulating angiogenesis. We demonstrated that S100A4 synergizes with vascular endothelial growth factor (VEGF), via the RAGE receptor, in promoting endothelial cell migration by increasing KDR expression and MMP-9 activity. In vivo overexpression of S100A4 led to a significant increase in tumor growth and vascularization in a human melanoma xenograft M21 model.

Complex modulation of peptidolytic activity of cathepsin D by sphingolipids.

Cathepsin D is an aspartic peptidase involved in cellular processes including proliferation and apoptosis and implicated in human pathologies such as cancer and neurodegeneration. Our knowledge about the relationship between proteolysis and bioactive sphingolipids is still very limited. Here, we describe a complex pattern of modulation of the peptidolytic activity of cathepsin D by sphingolipids.

Cathepsin D propeptide: mechanism and regulation of its interaction with the catalytic core.

Propeptide blocks the active site in the inactive zymogen of cathepsin D and is cleaved off during zymogen activation. We have designed a set of peptidic fragments derived from the propeptide structure and evaluated their inhibitory potency against mature cathepsin D using a kinetic assay. Our mapping of the cathepsin D propeptide indicated two domains in the propeptide involved in the inhibitory interaction with the enzyme core: the active site "anchor" domain and the N-terminus of the propeptide.

From nonpeptide toward noncarbon protease inhibitors: metallacarboranes as specific and potent inhibitors of HIV protease.

HIV protease (PR) represents a prime target for rational drug design, and protease inhibitors (PI) are powerful antiviral drugs. Most of the current PIs are pseudopeptide compounds with limited bioavailability and stability, and their use is compromised by high costs, side effects, and development of resistant strains. In our search for novel PI structures, we have identified a group of inorganic compounds, icosahedral metallacarboranes, as candidates for a novel class of nonpeptidic PIs.

Activation processing of cathepsin H impairs recognition by its propeptide.

Free propeptides are known to function as inhibitors of the parental mature cysteine cathepsins. This general rule, however, does not apply to the aminopeptidase cathepsin H. Screening of propeptide fragments for their inhibitory potency revealed no significant effect on the native mature cathepsin H.

Expression profiles of a human pancreatic cancer cell line upon induction of apoptosis search for modulators in cancer therapy.

We analyzed the differential gene expression in the pancreatic cancer cell line NP-18 upon induction of apoptosis caused by cyclin-dependent kinase inhibition triggered by either overexpression of the tumor suppressor gene p16(INK4A)using an adenoviral construction or incubation with the chemical inhibitors, roscovitine or olomoucine. Screening was performed using cDNA arrays from Clontech that allowed the determination of the expression of 1,176 genes specifically related with cancer. The analysis was carried out using the Atlas Image 2.

Horizontal sub-surface flow constructed wetland with pulsing water level.

A constructed wetland with horizontal sub-surface flow at Dolni Mesto (Czech Republic) was put into operation in 1999 and treats municipal wastewater from 522 PE. The total area of vegetated beds of 2,646 m2 is divided into two parallel sections of equal size, each with two beds in series. Between two periods of water discharge there is no outflow from the bed.