Current Pharmaceutical Biotechnology - Volume 17, Issue 10, 2016

Fetal or intrauterine growth restriction (FGR or IUGR) is a concerning health issue not only due to its implications in mortality and morbidity of neonates but also because of its long-term consequences on health and disease risk of the individuals. Its main cause is an insufficient supply of nutrients and oxygen by maternal (malnutrition or hypobaric hypoxia) or placental factors (placental insufficiency) during late gestation, when the requirements of fetus are higher. The availability of reliable animal models would be highly useful for the future development of diagnostic, preventive and therapeutic strategies. Most of the studies using animal models have been performed in rodents, while the use of large animals (sheep and swine) has been scarce. The objective of the current review is to offer an overview on the possibilities of using large animals for conducting translational research on IUGR related to inadequate maternal conditions and/or placental dysfunction.

Recent pan-cancer studies have shown the importance of coupling DNA methylation patterns with transcriptome profiles to reveal tumor subgroups with clinically relevant distinct characteristics. While the coupling patterns remain in most cases matter for further study and/or interpretation, it is emerging that all associations between epigenetic changes and specific cancer histotypes can facilitate the development of novel epidrugs. In particular, together with chemotherapy and chemoprevention of cancer, these epidrugs will target specific enzymes involved in the complex regulation of gene expression. This perspective surveys recent cancer epigenetic findings on target drugs and therapeutic strategies, and focuses on the epigenetic modifications that can reverse a stable differentiated state of adult cell towards neoplastic phenotypes. The relevance of such developments may thus pave the way for patient’s customized personalized therapies.

This is a literature review of studies focusing on the preparation of hydrogels for use as oncological drug delivery systems in the treatment of osteosarcoma (OS). The databases of the US National Library of Medicine National Institutes of Health, Embase, OVID, and Cochrane Library, and the references of retrieved studies, were traced from 1843 to December 21, 2015, without language restrictions. The obtained data were evaluated by complementary statistical methods. Potentially relevant studies were found and included in the analysis. OS-specific chemotherapeutic agents can be successfully embedded within the hydrogels and these drug-loaded hydrogels can be applied locally, rather than systemically, without organ tissue toxicity. Further, OS-specific drug-loaded hydrogels significantly increased tumor inhibition and decreased osteolysis and lung metastases. Drug-loaded hydrogels could be useful in the treatment of OS, although their development remains at the experimental phase. Following evaluation of their application in surgery and the completion of drug release kinetics studies, drug-loaded hydrogels could be tested on living mammals in large samples with the aim of applying these in clinical settings. In the future, development of such drug delivery systems and application of targeted approaches against osteosarcoma and other malignancies may render surgery, radiotherapy and chemotherapy unnecessary.

Iron oxide micro and nanoparticles were successfully synthesized from Red Mud (RM) using a simple twostep process. RM was characterized using various techniques such as X-Ray Diffractometer (XRD), Fourier Transform- Infra Red (FTIR) spectroscopy, Scanning Electron Microscopy (SEM), Energy Dispersive X-ray (EDX) analysis and Carbon Hydrogen Nitrogen (CHN) microanalysis. Red mud derived iron oxide micro and nanoparticles (RIMNP) were characterized using techniques such as XRD, FTIR, SEM/EDX, Transmission Electron Microscopy (TEM) and Vibrating Sample Magnetometry (VSM). RIMNP were employed as a Fenton like catalyst for the decolorization of a commonly used textile dye Reactive Blue 235 (RB235) from aqueous solution. The dynamical data obtained at different concentrations of RIMNP fit well with pseudo-second-order kinetic model and 100% dye removal efficiency was obtained at 200 mg L-1 concentration of RIMNP.

Statins are potent modulators of immune responses, resulting in their ability to enhance host survival from primary bacterial infections. Alterations in primary immune responses that may be beneficial for survival following infection may also result in alterations in the generation of the immunologic memory response and subsequently affect immune responses mounted during secondary bacterial infection. In this study, we report that levels of total serum IgG2c, following primary infection, were decreased in simvastatin pretreated mice, and investigate the effect of simvastatin treatment, prior to primary infection, on immune responses activated during secondary S. aureus infection. A secondary infection model was implemented whereby simvastatin pretreated and control mice were reinfected with S. aureus 14 days after primary infection, with no additional simvastatin treatment, and assessed for survival and alterations in immune function. While survivability to secondary S. aureus infection was not different between simvastatin pretreated and control mice, memory B and T lymphocyte functions were altered. Memory B cells, isolated 14 days after secondary infection, from simvastatin pretreated mice and stimulated ex vivo produced increased levels of IgG1 compared to memory B cells isolated from control mice, while levels of IgM and IgG2c remained similar. Furthermore, memory B and T lymphocytes from simvastatin pretreated mice exhibited a decreased proliferative response when stimulated ex vivo compared to memory cells isolated from control mice. These findings demonstrate the ability of a short term, low dose simvastatin treatment to modulate memory immune function.

The oral cavity, which harbors more than 750 bacterial species, is one of the most diverse sites of the human body. Some of these bacteria have been associated with oral diseases, such as dental caries and endodontic infections. We report on the antimicrobial and cytotoxic activities of Copaifera oblongifolia oleoresin against bacteria that cause caries and endodontic infections. The aim of this study is to determine the minimum (MIC) and the bactericidal (MBC) inhibitory concentrations as well as the biofilm inhibition ability (through determination of MBIC50) of the C. oblongifolia oleoresin. This study also investigated the bactericidal kinetics (time-kill curves) and the synergistic effect of the C. oblongifolia oleoresin. Additionally, this study evaluated the cytotoxic activity of the oleoresin toward V79 cells by means of the colony-forming assay. The C. oblongifolia oleoresin gave promising MIC and MBC values, which ranged from 25 to 200 μg/mL. Analysis of the MBIC50 values of the oleoresin revealed it displayed biofilm inhibitory activity against all the assayed bacteria. Analysis of the bactericidal kinetics showed different behaviors of the oleoresin against the tested bacteria at the different time intervals and concentrations assayed in this study. An additive effect of the oleoresin with chlorhexidine dihydrochloride occurred only for S. mitis and A. actinomycetemcomitans. The C. oblongifolia oleoresin showed cytotoxic activity at concentrations ≥ 625 μg/mL.

The influence of thermal and shear stressors on the stability of the anti-TNF-α monoclonal antibody (mAb), Infliximab® (INF) was investigated. INF at concentrations of 1, 4 and 10 mg/ml was subjected to thermal stress at temperatures of 25-65°C and to shear force by sonication for 1 and 3 minutes. The stressed samples were analysed for physical properties by particle size, zeta potential, for structural integrity by gel electrophoresis (SDS-PAGE) and circular dichroism, INF content by UV spectroscopy and for biological activity by ELISA. Results show no change in physical properties or structural integrity of INF at any concentration tested, when subjected to a temperature of up to 50°C. At 65°C, aggregation and precipitation of INF was observed. When subjected to shear stress, higher concentrations of INF at 4 and 10mg/ml maintained their physical properties and structural integrity. However, the biological activity of INF was found to decrease with increasing temperature and sonication time, and was concentration dependent (ANOVA; p<0.05). Interestingly, lyophilisation of INF at 1mg/ml did not affect its physical properties, structural integrity or its biological activity. These findings have important implications with respect to pharmaceutical processing of INF and mAbs including formulation as polymeric micro and nanoparticle systems for sustained or targeted delivery. These findings also have important implications with respect to the handling and storage of INF and mAbs for clinical use.

Background: Star fruit (Averrhoa carambola) is a well-known plant in Malaysia which bears a great significance in traditional medicine. Objectives: This study aimed to evaluate the antihyperlipidemic effect, antioxidant potential and cytotoxicity of aqueous and methanolic extracts of ripe and unripe fruits, leaves and stem of A. carambola. Methods: Antihyperlipidemic activity was assessed in poloxamer-407 (P-407) induced acute hyperlipidemic rat’s model. The antioxidant activity was assessed in vitro using 2, 2’-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical scavenging, 1-diphenyl-2-dipicrylhydrazyl radical scavenging (DPPH) and ferric reducing antioxidant power (FRAP) assays. In addition, cytotoxicity of A. carambola extracts was assessed using MTS assay on four leukemic cell lines (human colon cancer, human promyeloid leukemia, erythroid leukemia, acute myeloid leukemia) and one normal cell (human umbilical vein endothelial cells). Results: Methanolic extract of leaves had the most potent antihyperlipidemic activity in P-407 model, whereby it significantly reduced serum levels of total cholesterol (P<0.01), triglycerides (P<0.01), low-density lipoprotein (P<0.05), verylow- density lipoprotein (P<0.01) and atherogenic index (P<0.01). On the other hand, methanolic extracts of A. carambola stem and leaves showed the strongest antioxidant activity. Total phenolic and flavonoid contents of the extracts exhibited significant correlations with antioxidant but not with antihyperlipidemic activities. All plant parts showed no cytotoxic effect on the selected cancer or normal cell lines. Conclusion: Antihyperlipidemic activity of different parts of A. carambola is greatly affected by extraction solvents used. Methanolic extract of A. carambola leaves exhibited higher antihyperlipidemic and antioxidant potentials compared to other parts of the plant.

Many unsolved practical issues, from technical and scientific to ethical, legal and economic topics, are slowing down the translation of Personalized Medicine principles into medical practice. The Italian Society of Personalized Medicine exposes here its point of view, based on the real-world practice of precision medicine carried-out in Italian healthcare structures.