Angiogenesis is a process associated with the migration and proliferation of endothelial cells (EC) to form new blood vessels. It is involved in various physiological and pathophysiological conditions and is controlled by a wide range of proangiogenic and antiangiogenic molecules. The plasminogen activator–plasmin system plays a major role in the extracellular matrix remodeling process necessary for angiogenesis. Urokinase/tissue-type plasminogen activators (uPA/tPA) convert plasminogen into the active enzyme plasmin, which in turn activates matrix metalloproteinases and degrades the extracellular matrix releasing growth factors and proangiogenic molecules such as the vascular endothelial growth factor (VEGF-A). The plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of uPA and tPA, thereby an inhibitor of pericellular proteolysis and intravascular fibrinolysis, respectively. Paradoxically, PAI-1, which is expressed by EC during angiogenesis, is elevated in several cancers and is found to promote angiogenesis by regulating plasmin-mediated proteolysis and by promoting cellular migration through vitronectin. The urokinase-type plasminogen activator receptor (uPAR) also induces EC cellular migration during angiogenesis via interacting with signaling partners. Understanding the molecular functions of the plasminogen activator plasmin system and targeting angiogenesis via blocking serine proteases or their interactions with other molecules is one of the major therapeutic strategies scientists have been attracted to in controlling tumor growth and other pathological conditions characterized by neovascularization.
A green and cost-effective technique for the preparation of silver nanoparticles (Algae-AgNPs) as a colorimetric sensor for hydrogen peroxide (H2O2) is described. Silver nanoparticles were capped using the green algae (Noctiluca scintillans) extract at an optimum time of 3 h at 80 °C. The pH of the plant extract (pH = 7.0) yields nanoparticles with a mean size of 4.13 nm and a zeta potential of 0.200 ± 0.02 mV and negative polarity, using dynamic light scattering (DLS). High-resolution transmission electron microscopy (HRTEM) analysis showed regular spherical particles with the average size of 4.5 nm. Selected area electron diffraction (SAED) results revealed the polycrystalline nature of the silver nanoparticles. The obtained patterns were indexed as (111), (200), (220), and (311) reflections of the fcc (face centered cubic) silver crystal based on their d-spacing of 2.47, 2.13, 1.49, and 1.27 Å, respectively. The apparent color change from brown to colorless was observed when nanoparticles reacted with H2O2. Linear responses were obtained in three different ranges (nM, µM, and mM). Limits of detection (LOD) of 1.33 ± 0.02 and 1.77 ± 0.02 nM and quantitation limits (LOQ) of 7.31 ± 0.03 and 9.67 ± 0.03 nM were obtained for Abs and ΔAbs calibration curves, respectively. 10% v/v Algae-AgNPs solution inhibited Staphylococcus aureus over Escherichia coli, while a 50% reduction of tumor cell growth of MDA-MB-231 human breast adenocarcinoma was obtained.
Obesity is a major risk for diabetes. Brown adipose tissue (BAT) mediates production of heat while white adipose tissue (WAT) function in the storage of fat. Roles of BAT in the treatment of obesity and related disorders warrants more investigation. Peroxisome proliferator activator receptor gamma (PPAR-γ) is the master regulator of both BAT and WAT adipogenesis and has roles in glucose and fatty acid metabolism. Adipose tissue is the major expression site for PPAR-γ. In this study, the effects of rosiglitazone on the brown adipogenesis and the association of MAPK and PI3K pathways was investigated during the in vitro adipogenic differentiation of telomerase transformed mesenchymal stromal cells (iMSCs). Our data indicate that 2 µM rosiglitazone enhanced adipogenesis by over-expression of PPAR-γ and C/EBP-α. More specifically, brown adipogenesis was enhanced by the upregulation of EBF2 and UCP-1 and evidenced by multilocular fatty droplets morphology of the differentiated adipocytes. We also found that rosiglitazone significantly activated MAPK and PI3K pathways at the maturation stage of differentiation. Overall, the results indicate that rosiglitazone induced overexpression of PPAR-γ that in turn enhanced adipogenesis, particularly browning adipogenesis. This study reports the browning effects of rosiglitazone during the differentiation of iMSCs into adipocytes in association with the activation of MAPK and PI3K signaling pathways.
In recent years, metallic nanoparticles have gained increasing attention due to their prospective applications in the field of nanomedicine, with increasing research into their use in cancer therapy. In this current research, we investigated the effect of green synthesized Silver Nanoparticles (AgNPs) capped with Noctiluca scintillans algae extract. The phytochemicals present in the shell of AgNPs were identified using GC-MS. Different compounds with anticancer activity such as n-hexadecanoic acid, beta-sitosterol, stigmasterol and palmitic acid were detected among others. The effects of Algae-AgNPs synthesized were tested on MDA-MB-231 human breast cancer cells and HaCat human keratinocyte normal cells. Cell viability assay revealed a time and dose-dependent effect against breast cancer cells with a less potent effect against normal cells. The cell viability reduction is not attributed to a cytotoxic nor an antiproliferative effect of the Algae-AgNPs as attested by LDH release and BrdU incorporation. Algae-AgNPs exhibited an exceptional ability to specifically induce apoptosis in cancer cells and not normal cells. The observed effects are not attributed to the AgNPs, as demonstrated by the lack of impact of the Starch-AgNPs (used as a negative control) on cell survival and apoptosis. In addition to that, we show that Algae-AgNPs significantly reduced tumor cell migration by downregulation of matrix metalloprotease-9 levels. In vivo, the breast cancer xenograft model showed a significant reduction of tumor growth in mice treated with Algae-AgNPs. These findings highlight the promising potential of the green synthesized AgNPs as a safe targeted therapy for cancer treatment.
: Protein denaturation in frozen minced fillets (Ehrenberg’s Snapper), stored at −25°C was studied; 50.0 mg biomass/50g mince fillets treated with cinnamon, cumin, turmeric, garlic, ginger and 25.0 mg of vitamin C were used to slow protein denaturation. FT-IR stretching vibration of Amide-A (νNH) at 3300 cm−1; Amide-I stretching (νC=O) between 1600−1690 cm−1 and Amide-II stretching (νCN) and bending (δNH) between 1480 and 1575cm−1 were used as marker peaks. Garlic was the most significant (P ≤0.01) in controlling the rate of protein denaturation when νNH was used as a marker peak. DSC analysis showed that turmeric presented the highest effect on delaying the denaturation of sarcoplasmic proteins with a ∆H0=73.7J/g followed by garlic-treated mince fillets ∆H0=70.1J/g. All spices used were efficient in stopping the denaturation of myosin with the highest ∆H0=769.3 J/g registered for cinnamon-treated mince fillets. Actin was less vulnerable to denaturation in comparison to myosin and sarcoplasmic proteins.
The 14-kilodalton human growth hormone (14 kDa hGH) N-terminal fragment derived from the proteolytic cleavage of its full-length counterpart has been shown to sustain antiangiogenic potentials. This study investigated the antitumoral and antimetastatic effects of 14 kDa hGH on B16-F10 murine melanoma cells. B16-F10 murine melanoma cells transfected with 14 kDa hGH expression vectors showed a significant reduction in cellular proliferation and migration associated with an increase in cell apoptosis in vitro. In vivo, 14 kDa hGH mitigated tumor growth and metastasis of B16-F10 cells and was associated with a significant reduction in tumor angiogenesis. Similarly, 14 kDa hGH expression reduced human brain microvascular endothelial (HBME) cell proliferation, migration, and tube formation abilities and triggered apoptosis in vitro. The antiangiogenic effects of 14 kDa hGH on HBME cells were abolished when we stably downregulated plasminogen activator inhibitor-1 (PAI-1) expression in vitro. In this study, we showed the potential anticancer role of 14 kDa hGH, its ability to inhibit primary tumor growth and metastasis establishment, and the possible involvement of PAI-1 in promoting its antiangiogenic effects. Therefore, these results suggest that the 14 kDa hGH fragment can be used as a therapeutic molecule to inhibit angiogenesis and cancer progression.