[Show abstract][Hide abstract] ABSTRACT: Angiogenesis is an essential process for organ growth and repair. Thus, an imbalance in this process can lead to several diseases including malignancy. Angiogenesis is a critical step in vascular remodeling, tissue damage and wound healing besides being required for invasive tumor growth and metastasis. Because angiogenesis sets an important point in the control of tumor progression, its inhibition is considered a valuable therapeutic approach for tumor treatment. Chronic liver disease including hepatitis C virus (HCV) infection is one of the main cause for the development of hepatic angiogenesis and thereby plays a critical role in the modulation of hepatic angiogenesis that finally leads to hepatocellular carcinoma progression and invasion. Thus, understanding of the molecular mechanisms of HCV-mediated hepatic angiogenesis will help design a therapeutic protocol for the intervention of HCV-mediated angiogenesis and subsequently its outcome. In this review, we will focus on the molecular mechanisms of HCV-mediated hepatic angiogenesis and the related signaling pathways that can be target for current and under development therapeutic approaches.
[Show abstract][Hide abstract] ABSTRACT: Despite the availability of melanoma treatment at the primary site, the recurrence of local melanoma can metastasize to any distant organ. Currently, the available therapies for the treatment of metastatic melanoma are of limited benefit. Thus, the functional analysis of conventional therapies may help to improve their efficiency in the treatment of metastatic melanoma. In the present study, the exposure of melanoma cells to vinblastine was found to trigger apoptosis as evidenced by the loss of mitochondrial membrane potential, the release of both cytochrome c and apoptosis inducing factor, activation of caspase-9 and 3, and cleavage of Poly (ADP-ribose)-Polymerase. Also, vinblastine enhances the phosphorylation of Ras homologous protein A, the accumulation of reactive oxygen species, the release of intracellular Ca(2+), as well as the activation of apoptosis signal-regulating kinase 1, c-jun-N-terminal kinase, p38, inhibitor of kappaBα (IκBα) kinase, and inositol requiring enzyme 1α. In addition, vinblastine induces the DNA-binding activities of the transcription factor NF-κB, HSF1, AP-1, and ATF-2, together with the expression of HSP70 and Bax proteins. Moreover, inhibitory experiments addressed a central role for Rho A in the regulation of vinblastine-induced apoptosis of melanoma cells via mitochondrial and non-mitochondrial-dependent mechanisms. In conclusion, the present study addresses for the first time a central role for Rho A in the modulation of vinblastine-induced apoptosis of melanoma cells and thereby provides an insight into the molecular action of vinblastine in melanoma treatment.
[Show abstract][Hide abstract] ABSTRACT: Viridans streptococci possess a family of immunologically and structurally related cell-surface proteins, termed antigen I/II, which may function as adhesins and enable oral streptococci to adhere to saliva-coated surfaces and matrix proteins. Here we used atomic force microscopy in the molecular force mode to measure the specific interaction forces between antigen I/II and two matrix proteins, collagen and fibronectin. These matrix proteins provide important binding sites for adherence of oral streptococcal in dentinal caries and endocarditis, respectively. Antigen I/II-coated cantilever tips were brought into contact with collagen- or fibronectin-coated silica coverslips. For the protein I/II-fibronectin interaction experiments, the mean strength of the last ruptures was 216 pN, with most of the detachments located around 125 pN. In antigen I/II-collagen interaction experiments, the mean strength of the last rupture forces corresponded to 136 pN, with the most frequent unbinding force around 75 pN. Thus, our findings definitely suggest that, under the present experimental conditions, antigen I/II binds more strongly to fibronectin than to type I collagen. This might be of relevance for the attachment of viridians streptococci to surfaces exposed to strong hydrodynamic shearing forces under in vivo conditions.
European Journal Of Oral Sciences 12/2010; 118(6):590-5. DOI:10.1111/j.1600-0722.2010.00785.x · 1.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chromogranin A is present in secretion granules of nerve, endocrine and immune cells and is a precursor of several peptides with antibacterial and antifungal properties at micromolar concentrations.Our aim in this prospective, double blind study, was to determine the expression of chromogranin A and its peptides at protein level in saliva of type 2 diabetic patients and thereby to obtain a new non-invasive diagnostic means for the future.Saliva was taken from 30 type 2 diabetic patients and 30 healthy individuals at the same time interval in the morning without any oral stimuli. Circadianic periodics in protein productions have been avoided. The presence of chromogranin A and its derived peptides was determined in whole saliva, after centrifugation at 40C for 12 min at 14 000 rpm, by SDS-PAGE electrophoresis and Immunoblotting (Western Blot). To ensure same protein concentrations Bradford protein quantification assay has been performed before.For the first time, we have determined an overexpression of chromogranin A in saliva of diabetic patients in 100% of the individuals. Chromogranin A, a circulating biomarker for epithelial tumours, is also overexpressed in saliva of type 2 diabetic patients. To confirm our results, more studies with a large amount of patients is necessary.
Bosnian journal of basic medical sciences / Udruzenje basicnih mediciniskih znanosti = Association of Basic Medical Sciences 02/2010; 10(1):2-8. · 0.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Regenerative therapy with enamel matrix proteins derivative (EMD) was shown to induce periodontal regeneration in intrabony defects. However, the contribution of papilla preservation technique (PPT), to the clinical outcome of regenerative therapy is still not clarified. Therefore, we conducted the present study to evaluate clinically measurable results of a combined therapy by PPT and EMD in the treatment of isolated intrabony defects.
Sixty isolated intrabony defects in 25 patients were surgically assessed with EMD and PPT. The clinical parameters: clinical attachment level (CAL), probing depth (PD) and gingival recession (GR) were evaluated at baseline and at three years.
The primary outcome variable was CAL. The sites treated with enamel matrix proteins demonstrated mean CAL change from 6.6+/-1.2 mm to 3.4+/-1.3 mm (p<0.001) and the mean PD was reduced from 5.9+/-1.0 mm to 2.7+/-0.8 mm (p<0.001) after three years. The mean GR decreased from 0.71+/-1.2 mm to 0.64+/-1.1 mm (p<0.821).
The results of the present case cohort study indicate that PPT combined with EMD resulted in significant improvement of the clinical parameters in the treatment of intrabony defects in chronic periodontitis.
Stomatologija / issued by public institution "Odontologijos studija" ... [et al.] 01/2008; 10(1):22-6.
[Show abstract][Hide abstract] ABSTRACT: Diabetes mellitus is a common and growing global health problem leading to several complications. Among these periodontal diseases are considered as the sixth complication of diabetes mellitus. This article reviews the relationship between diabetes and oral health, particularly focusing on periodontal diseases, dental caries and xerostomia. There is a bidirectional interrelationship between diabetes and periodontal diseases. Periodontitis is more prevalent and severe in patients with diabetes than in normal population. Therapy of periodontal infection contributes to a positive glycaemic control management and enables reduction of the burden of complications of diabetes mellitus. Diabetics have an increased predisposition to the manifestation of oral diseases like candidiasis which is associated with poor glycaemic control and therapeutic dentures. This predisposition also contributes to xerostomia, which may be due to increased glucose levels in oral fluids or immune dysregulation.