Early Effects of P-15 on Human Bone Marrow Stem Cells

OBJECTIVES: Peptide-15 (P-15) is an analogue of the cell binding domain of collagen. P-15 has been shown to facilitate physiological to process in a way similar to collagen, to serve as anchorage for cells, and to promote the binding, migration and differentiation of cells. However, how P-15 alters osteoblast activity to promote bone formation is poorly understood. To study the osteoinductive properties of peptide P-15, we analyzed the expression levels of bone related genes in human mesenchymal stem cells treated with this biomaterial. MATERIAL AND METHODS: Using real time Reverse Transcription-Polymerase Chain Reaction the quantitative expression of specific genes, like transcriptional factors (RUNX2 and SP7), bone related genes (SPP1, COL1A1, COL3A1, BGLAP, ALPL, and FOSL1) and mesenchymal stem cells marker (ENG) were examined. RESULTS: P-15 causes a considerable induction of osteoblast transcriptional factor like osterix (SP7) and of the bone related genes osteopontin (SPP1) and osteocalcin (BGLAP). In contrast the expression of endoglin (ENG) was markedly decreased in stem cells treated with P-15 respect to untreated cells, indicating the differentiation effect of this biomaterial on stem cells. CONCLUSIONS: The present study shows the effect of P-15 on mesenchymal stem cells in the early differentiation stages: P-15 is an inducer of osteogenesis on human stem cells as indicated by the activation of bone related markers SP7, SPP1 and BGLAP.The results may allow a better understanding of the molecular mechanism of bone regeneration and as a model for comparing other materials with similar clinical effects

Differences between eccentric and rotary tablet machines in the evaluation of powder densification behaviour

Differences in the dynamics of powder densification between eccentric and rotary machine were pointed out by compressing at different compression pressures microcrystal line cellulose, lactose monohydrate and dicalcium phosphate dihydrate and recovering the corresponding stress/strain data in both machines equipped to monitor punches displacement and compression forces. Heckel plots were then obtained from these stress/strain data. Curves obtained in the rotary machine possess a narrower zone of linearity for the calculation of P-Y and D-A. The effect of the different compression mechanism of the rotary machine on the shape of the Heckel plot is more noticeable in a non-deforming material such as dicalcium phosphate. The effect of the longer dwell time of the rotary machine on the porosity reduction occurring after the maximum pressure has been reached, is more noticeable in a ductile material such as microcrystalline cellulose. Heckel parameters obtained in the rotary press are in some cases different from those recovered in the eccentric machine because of the longer dwell time, machine deflection and punch tilting occurring in the rotary machine, although theoretically they could better describe the material densification in a high speed production rotary machine

Biology of Drug-Induced Gingival Hyperplasia: In Vitro Study of the Effect of Nifedipine on Human Fibroblasts

Background: It has been proven that the antihypertensive agent nifedipine can cause gingival overgrowth as a side effect. The aim of this study was to analyze the effects of pharmacological treatment with nifedipine on human gingival fibroblasts activity, investigating the possible pathogenetic mechanisms that lead to the onset of gingival enlargement. Methods: The expression profile of 57 genes belonging to the “Extracellular Matrix and Adhesion Molecules” pathway, fibroblasts’ viability at different drug concentrations, and E-cadherin levels in treated fibroblasts were assessed using real-time Polymerase Chain Reaction, PrestoBlue™ cell viability test, and an enzyme-linked immunoassay (ELISA), respectively. Results: Metalloproteinase 24 and 8 (MMP24, MMP8) showed significant upregulation in treated cells with respect to the control group, and cell adhesion gene CDH1 (E-cadherin) levels were recorded as increased in treated fibroblasts using both real-time PCR and ELISA. Downregulation was observed for transmembrane receptors ITGA6 and ITGB4, the basement membrane constituent LAMA1 and LAMB1, and the extracellular matrix protease MMP11, MMP16, and MMP26. Conclusions: The obtained data suggested that the pathogenesis of nifedipine-induced gingival overgrowth is characterized by an excessive accumulation of collagen due to the inhibition of collagen intracellular and extracellular degradation pathways

Editorial: Metabolism Meets Function: Untangling the Cross-Talk Between Signaling and Metabolism

Tumor metabolism is a long established field in cancer biology, as the seminal findings of Otto Warburg date back to the 1920s. Since then, the discovery that oncogenes, besides promoting the Warburg effect, modulate anabolic pathways, has prompted scientists to re-evaluate the role that tumor metabolism plays in the neoplastic process. Today, metabolic reprogramming of neoplastic cells is considered a hallmark of cancer, with the discovery that flexibility in the acquisition of various cellular characteristics is supported by specific metabolic pathways. Clinical and pharmacological advances, for example the application of FDG-PET in the clinical setting (1) and the development of novel pharmacological strategies based on antimetabolites (2), provide further support and validation of the role of metabolism in cancer. Here, we present a collection of works with the aim of bringing together work from a variety of scientists across the field of tumor metabolism toward an understanding of how different metabolic pathways are activated in neoplastic and surrounding cells, the mechanisms linking altered metabolism to tumorigenesis and the potential for pharmacological applications

Development of Biodegradable PBS/PVOH-based Films and Evaluation of Performance for Food Packaging Applications

The objective of this work deals with the realization of high O2-barrier blown films based on novel biodegradable blends of Polybutylene succinate (PBS) and Poly-vinyl alcohol (PVOH) for food packaging applications. Blends at different PBS/PVOH weight ratios (100/0, 80/20, 60/40, 0/100 wt%) were produced and their processability and miscibility was preliminary assessed by means of dynamic shear rheological tests. Afterwards, blown films were realized and then characterized in terms of chemical properties and oxygen barrier performance. The results revealed that, although immiscible, polymers in the blend show some degree of interaction. Moreover, as the concentration of PVOH in the films increased, a significant decrease in oxygen permeability was obtained with respect to the neat PBS film, up to 42% for the PBS/PVOH 60/40 sample. The findings of this study highlighted the promising perspectives of these films as sustainable packaging for sensitive foods with high O2-barrier requirements

Polymorphic variants of IGF2BP3 and SENCR have an impact on predisposition and/or progression of Ewing sarcoma

Ewing sarcoma (EWS), the second most common malignant bone tumor in children and adolescents, occurs abruptly without clear evidence of tumor history or progression. Previous association studies have identified some inherited variants associated with the risk of developing EWS but a common picture of the germline susceptibility to this tumor remains largely unclear. Here, we examine the association between thirty single nucleotide polymorphisms (SNPs) of the IGF2BP3, a gene that codes for an oncofetal RNA-binding protein demonstrated to be important for EWS patient's risk stratification, and five SNPs of SENCR, a long non-coding RNA shown to regulate IGF2BP3. An association between polymorphisms and EWS susceptibility was observed for three IGF2BP3 SNPs - rs112316332, rs13242065, rs12700421 - and for four SENCR SNPs - rs10893909, rs11221437, rs12420823, rs4526784 -. In addition, IGF2BP3 rs34033684 and SENCR rs10893909 variants increased the risk for female respect to male subgroup when carried together, while IGF2BP3 rs13242065 or rs76983703 variants reduced the probability of a disease later onset (> 14 years). Moreover, the absence of IGF2BP3 rs10488282 variant and the presence of rs199653 or rs35875486 variant were significantly associated with a worse survival in EWS patients with localized disease at diagnosis. Overall, our data provide the first evidence linking genetic variants of IGF2BP3 and its modulator SENCR to the risk of EWS development and to disease progression, thus supporting the concept that heritable factors can influence susceptibility to EWS and may help to predict patient prognosis

Berberine and Tinospora cordifolia exert a potential anticancer effect on colon cancer cells by acting on specific pathways

Berberine (BBR) is a natural active principle with potential antitumor activity. The compound targets multiple cell signaling pathways, including proliferation, differentiation, and epithelial-mesenchymal transition. The aim of this study was to elucidate the mechanisms behind the anticancer activity of BBR by comparing the effects of purified BBR with those of the extract of Tinospora cordifolia, a medicinal plant that produces this metabolite. The expression levels of a panel of 44 selected genes in human colon adenocarcinoma (HCA-7) cell line were quantified by real-time polymerase chain reaction (PCR). BBR treatment resulted in a time- and dose-dependent down regulation of 33 genes differently involved in cell cycle, differentiation, and epithelial-mesenchymal transition. The trend was confirmed across the two types of treatment, the two time points, and the different absolute dosage of BBR. These findings suggest that the presence of BBR in T. cordifolia extract significantly contributes to its antiproliferative activity

Design, synthesis and preliminary pharmacological evaluation of new imidazolinonesas L-DOPA prodrugs

L-DOPA, the immediate biological precursor of dopamine, is still considered the drug of choice in the treatment of Parkinson's disease. However, therapy with L-DOPA is associated with a number of acute problems. With the aim to increase the bioavailability after oral administration, we designed a multi-protected L-DOPA prodrugs able to release the drug by both spontaneous chemical or enzyme catalyzed hydrolysis. The new compounds have been synthesized and preliminarily evaluated for their water solubility, log P, chemical stability, and enzymatic stability. The results indicate that the incorporation of the amino acidic moiety of L-DOPA into an imidazoline-4-one ring provides prodrugs sufficiently stable to potentially cross unchanged the acidic environment of the stomach, and to be absorbed from the intestine. They also might be able to release L-DOPA in human plasma after enzymatic hydrolysis. The ability of prodrugs 6a-b to increase basal levels of striatal DA, and influence brain neurochemistry associated with dopaminergic activity following oral administration, as well as the radical-scavenging activity against DPPH for compounds 6a-b and 15a are also reported

First description of partial atrioventricular septal defect in a rabbit

Congenital heart diseases have rarely been described in rabbits. The purpose of the present case report is to describe the clinical, radiographic, echocardiographic, and pathological features of a partial atrioventricular septal defect in a pet rabbit. A 3-month-old, 380-g male vaccinated pet rabbit was presented for decreased activity, increased respiratory rate and effort, anorexia, and decreased fecal output of 2 days duration. Total body radiographic images revealed severe cardiomegaly associated with enlarged caudal pulmonary vessels and increased interstitial to alveolar lung pattern. Echocardiographic imaging showed evidence of distended heart chambers, abnormal flow through the atria, and mitral valve regurgitation. The rabbit was treated with furosemide and an angiotensin-converting enzyme inhibitor but rapidly deteriorated and died. Necropsy confirmed the dilation of both ventricles and the presence of a partial atrioventricular septal defect associated with an ostium primum atrial septal defect just over the tricuspid valve and the mitral valve

Isolation and characterization of cancer stem cells in head and neck squamous cell carcinoma

The hypothesis that a small subset of cells with characteristics of staminality is essential for the cancer onset has been widely studied in many tumors, included head-neck cancer, the seventh most common cancer in humans (1). These cells represent a small oncogenic subpopulation, with a characteristic phenotype that confers them a greater resistance to chemotherapy and radiotherapy (2). In this study the expression profile of some genes that differentiates cancer stem cells (CSC) from tumor cell of origin (TC) has been evaluated using Real Time PCR. Three cell lines, PE46, PE15 and HEP2, obtained from head and neck squamous cell carcinoma, where placed in culture, in absence of serum and in the presence of specific growth factors, giving rise to a spheroid cell subpopulation, with characteristics belonging to CSC. CSC were isolated using a selective filtration procedure based on beads labeled with the anti-CD44, that recognize a specific antigen of CSC in head and neck cancer (1). Few genes potentially involved in the onset and progression of oral cancer, were eval- uated in Real Time PCR, in order to compare their expression in CSC respect TC. All the three cell lines showed a common expression profile among the stem cell markers, resulting in an overexpression of the CD44 and ALDH1A in the spheroid population. Many of the investigated tumor markers were highly over-expressed in CSC, like TNFα, a pro-inflammatory factor that inhibits precancerous cell death, TP63, which is associated with an increase in the malignant transformation and a poor prognosis, and S100A4, a pro-inflammatory mediator involved in epithelial-mesenchymal transition of cancer cells. These results suggest the potential role of CSC in the tumor invasiveness. The characterization of CSC may lead to an improvement in the diagnosis and cancer therapy, allowing implementing treatments able to destroy cells which are probably involved in the process of metastasis