Short- and long-term effect of colorectal cancer targeting peptides conjugated to gold nanoparticles in rats' liver and colon after single exposure.

Peptides play important roles in the diagnosis, prognostic predictors, and treatment of various kinds of cancer. Peptides (p.C, p.L and p.14), derived from the phage display peptide libraries, specifically binds to colorectal cancer (CRC) cells in vitro. To allow tumor specificity and selectivity for in vivo diagnosis of CRC, biotinylated p.C, p.L and p.14 were conjugated to AuNPs (14 nm) via the biotin-streptavidin interaction. Male Wistar rats were intravenously injected with a single dose (100 µg/kg body weight) of AuNPs (citrate-AuNPs, PEG-AuNPs, p.C-PEG-, p.L-PEG- and p.14-PEG-AuNPs). Animals were monitored for behavioral changes, and sacrificed either 14 days or 84 days post-injection. Biochemical changes, oxidative stress, and histology of the liver and colon were assessed. No significant changes were noted in the rats injected with all the AuNPs, except p.L-PEG-AuNPs that caused significant toxicity (p < 0.05) 14 days post-exposure when compared to control group, as evidenced by increased relative liver weight, increased malondialdehyde levels and histological changes in the liver. These changes, however, returned to normalcy 84 days post-injection. It can be concluded, based on these findings, that p.L induced a transient toxicity in rats after a single intravenous injection, and can therefore be considered non-toxic long-term after a single exposure.

Review of physical stimulation techniques for assisting distraction osteogenesis in maxillofacial reconstruction applications.

Distraction Osteogenesis (DO) is an emerging limb lengthening method for the reconstruction of the hard tissue and the surrounding soft tissue, in different human body zones. DO plays an important role in treating bone defects in Maxillofacial Reconstruction Applications (MRA) due to reduced side effects and better formed bone tissue compared to conventional reconstruction methods i.e. autologous bone graft, and alloplast implantation. Recently, varying techniques have been evaluated to enhance the characteristics of the newly formed tissues and process parameters. Promising results have been shown in assisting DO treatments while benefiting bone formation mechanisms by using physical stimulation techniques, including photonic, electromagnetic, electrical, and mechanical stimulation technique. Using assisted DO techniques has provided superior results in the outcome of the DO procedure compared to a standard DO procedure. However, DO methods, as well as assisting technologies applied during the DO procedure, are still emerging. Studies and experiments on developed solutions related to this field have been limited to animal and clinical trials. In this review paper, recent advances in physical stimulation techniques and their effects on the outcome of the DO treatment in MRA are surveyed. By studying the effects of using assisting techniques during the DO treatment, enabling an ideal assisted DO technique in MRA can be possible. Although mentioned techniques have shown constructive effects during the DO procedure, there is still a need for more research and investigation to be done to fully understand the effects of assisting techniques and advanced technologies for use in an ultimate DO procedure in MRA.

In vitroanti-oxidant and cytotoxic activities of gold nanoparticles synthesized from an aqueous extract of theXylopia aethiopicafruit.

The development of gold nanoparticles (AuNPs) using a green approach has drawn considerable interest in the field of nanomedicine. Its wide application in clinical diagnosis, imaging and therapeutics portrays its importance for human existence. In this study, we reported on the biogenic synthesis of AuNPs using the aqueous extract of theXylopia aethiopicafruit (AEXAf), which acts as both a reducing and stabilizing agent. The characterization of AEXAf-AuNPs was performed using ultraviolet-visible spectroscopy, dynamic light scattering and zeta potential measurements, high-resolution transmission electron microscopy and Fourier transform-infrared spectroscopy. Thein vitroanti-oxidant activities of the AEXAf-AuNPs and AEXAf were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing anti-oxidant power. Thein vitrocytotoxic activities of the AEXAf-AuNPs and AEXAf against breast and colorectal cancer cells were evaluated using 3,-(4,5 dimethylthiazol)-2,5 diphenyl tetrazolium bromide (MTT) viability and annexin V/PI assays. The AEXAf-AuNPs exhibited surface plasmon absorption maximum at 522 nm and were stable for 4 weeks. The average size of the AEXAf-AuNPs was 10.61 ± 3.33 nm on the high-resolution transmission electron microscopy images. Thein vitroanti-oxidant activities of the AEXAf-AuNPs and AEXAf were concentration dependent. The AEXAf-AuNPs were cytotoxic to the cancer cells and non-toxic to the non-cancerous human fibroblast cells (KMST-6) (up to 200µg ml-1). From these results, the AEXAf-AuNPs showed good anti-oxidant and anti-cancer activities, and can be suggested as a possible therapeutic agent for breast and colorectal cancer.

Investigation of bioactive compounds in Crassocephalum rubens leaf and in vitro anticancer activity of its biosynthesized gold nanoparticles.

The development of cancer therapies has become difficult due to high metastasis, and lack of tissue selectivity, which in most cases affects normal cells. Demand for anticancer therapy is therefore increasing on daily basis. Gold nanoparticles (AuNPs) have many applications in biomedical field. Biological synthesis of AuNPs using aqueous extract of Crassocephalum rubens (AECR) was designed to investigate the in vitro anticancer potential. The synthesized AuNPs were characterized by UV-vis spectroscopy, high-resolution transmission electron microscopy, and Fourier transform infrared spectroscopy. The characterization results showed the formation of green AuNPs of wavelength 538 nm, and mostly spherical AuNPs with 20 ±â€¯5 nm size. Significant anticancer activity of the AECR-AuNPs on MCF-7 and Caco-2 cells was noted at higher concentrations (125 and 250 µg/mL) during 24 and at all concentrations tested during 48 h. It can therefore be concluded that AECR leaves can mediate stable AuNPs with anticancer properties.

Development and Evaluation of a Reconstitutable Dry Suspension Containing Isoniazid for Flexible Pediatric Dosing.

Tuberculosis (TB) is a major cause of childhood death. Despite the startling statistics, it is neglected globally as evidenced by treatment and clinical care schemes, mostly extrapolated from studies in adults. The objective of this study was to formulate and evaluate a reconstitutable dry suspension (RDS) containing isoniazid, a first-line anti-tubercular agent used in the treatment and prevention of TB infection in both children and adults. The RDS formulation was prepared by direct dispersion emulsification of an aqueous-lipid particulate interphase coupled with lyophilization and dry milling. The RDS appeared as a cream-white free-flowing powder with a semi-crystalline and microparticulate nature. Isoniazid release was characterized with an initial burst up to 5 minutes followed by a cumulative release of 67.88% ± 1.88% (pH 1.2), 60.18% ± 3.33% (pH 6.8), and 49.36% ± 2.83% (pH 7.4) over 2 hours. An extended release at pH 7.4 and 100% drug liberation was achieved within 300 minutes. The generated release profile best fitted the zero order kinetics (R2 = 0.976). RDS was re-dispersible and remained stable in the dried and reconstituted states over 4 months and 11 days, respectively, under common storage conditions.

In Vitro Analysis of the Combinatory Effects of Novel Aminonaphthoquinone Derivatives and Curcumin on Breast Cancer Progression.

BACKGROUND/AIM: We previously reported the potential of aminonaphthoquinone derivatives as therapeutic agents against breast and other oestrogen-responsive tumours when combined with curcumin. This study aimed at screening of novel aminonaphthoquinone derivatives (Rau 008, Rau 010, Rau 015 and Rau 018) combined with curcumin for cytotoxic, anti-angiogenic and anti-metastatic effects on MCF-7 and MDA-MB-231 breast cancer cells. MATERIALS AND METHODS: Cytotoxic and anti-angiogenic effects were analysed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and enzyme-linked immunosorbent assay; while anti-metastatic effects were measured using adhesion assay, Boyden chambers and Matrigel. RESULTS: Curcumin combined with Rau 008 elicited marked cytotoxic effects in MCF-7 cells compared with the individual treatments, whereas when it was combined with Rau 015 and with Rau 018, it displayed similar effects in MDA-MB-231 cells. The anti-angiogenic effect of Rau 015 plus curcumin in MCF-7 cells and Rau 018 plus curcumin in MDA-MB-231 cells was more effective than individual treatments, while the metastatic capability of MDA-MB-231 cells was significantly reduced after treatment with the aminonaphthoquinone-curcumin combinations. CONCLUSION: Aminonaphthoquinones may offer significant promise as therapeutic agents against breast cancer, particularly when combined with curcumin.

Toxicological Behavior of Gold Nanoparticles on Various Models: Influence of Physicochemical Properties and Other Factors.

Potential applications of gold nanoparticles in biomedicine have increasingly been reported on account of the ease of synthesis, bioinert characteristics, optical properties, chemical stability, high biocompatibility, and specificity. The safety of these particles remains a great concern, as there are differences among toxicity study protocols used. This article focuses on integrating results of research on the toxicological behavior of gold nanoparticles. This can be influenced by the physicochemical properties, including size, shape, surface charge, and other factors, such as methods used in the synthesis of gold nanoparticles, models used, dose, in vivo route of administration, and interference of gold nanoparticles with in vitro toxicity assay systems. Several researchers have reported toxicological studies with regard to gold nanoparticles, using various in vitro, in vivo, and in ovo models. The conflicting results concerning the toxicity of gold nanoparticles should thus be addressed to justify the safe use of gold nanoparticles in biomedicine.

Evaluation of the Effects of Aminonaphthoquinone Derivatives in Combination with Curcumin Against ER-positive Breast Cancer and Related Tumours.

BACKGROUND/AIM: Combination therapies are often explored to treat cancer. The use of curcumin as an adjuvant to current chemotherapies has been reported, whilst aminonaphthoquinones have shown potential as anticancer agents in various tumour cell lines. This study aimed at screening synthetic aminonathoquinone derivatives (Rau 008, Rau 010, Rau 015 and Rau 018) alone and in combination with curcumin for anti-breast cancer activity. MATERIALS AND METHODS: Combination effects were determined in MCF-7 breast cancer cells using combination index analyses. Synergistic anti-proliferative effects were further investigated in breast (MCF-7, MDA-MB-231), osteosarcoma (MG-63) and endometrial (HEC-1A) cancer-derived cells. RESULTS: Rau 015 (15 µM) and curcumin (112.5 µM) significantly reduced MCF-7, MDA-MB-231 and MG-63 cell proliferation compared to individual treatment, indicating synergistic anti-proliferative effects. Rau 018 (30 µM) and curcumin (100 µM) displayed similar effects in MCF-7 and MG-63 cells. CONCLUSION: We report on the potential of Rau 015 or Rau 018 as anti-breast cancer agents when combined with curcumin.

Synthesis and in vitro growth inhibitory activity of novel silyl- and trityl-modified nucleosides.

Seventeen silyl- and trityl-modified (5'-O- and 3',5'-di-O-) nucleosides were synthesized with the aim of investigating the in vitro antiproliferative activities of these nucleoside derivatives. A subset of the compounds was evaluated at a fixed concentration of 100µM against a small panel of tumor cell lines (HL-60, K-562, Jurkat, Caco-2 and HT-29). The entire set was also tested at varying concentrations against two human glioma lines (U373 and Hs683) to obtain GI50 values, with the best results being values of ∼25µM.

6-Substituted imidazo[1,2-a]pyridines: synthesis and biological activity against colon cancer cell lines HT-29 and Caco-2.

A range of 6-substituted imidazo[1,2-a]pyridines were synthesized using a multicomponent coupling reaction. Most of these compounds were found to exhibit excellent activity against the colon cancer cell lines HT-29 and Caco-2, whilst not showing significant toxicity against white blood cells. Our studies have shown that the proteolytic phase of apoptosis was initiated 2 h after treatment with these imidazo-[1,2-a]pyridines. The data suggests that the imidazo[1,2-a]pyridine-induced cell death in HT-29 and Caco-2 cells is mediated via pathway(s) that include the release of cytochrome c from the mitochondria to the cytosol and the activation of caspase 3 and caspase 8.

Endogenous heparin levels in the controlled asthmatic patient.

BACKGROUND: Since heparin possesses anti-inflammatory properties, it is hypothesised that asthmatic patients have decreased levels of circulating heparin compared with healthy individuals. DESIGN: We compared endogenous heparin levels in controlled asthmatic patients (53 adults) from the Asthma Clinic at Johannesburg General Hospital with those of healthy controls (26 adults) from the general population. Heparin levels in the blood samples were tested using the Chromogenix Coatest Heparin kit. RESULT: The blood of the patients contained significantly lower levels of endogenous heparin compared with that of the healthy individuals, indicating that the anti-inflammatory properties afforded by heparin are absent in these patients.

Cytotoxicity of purified cassava linamarin to a selected cancer cell lines.

Cassava (Manihot esculenta Crantz) is a known source of linamarin, but difficulties associated with its isolation have prevented it from being exploited as a major source. A batch adsorption process using activated carbon proved successful in its isolation, with ultrafiltration playing a pivotal role in its purification. Thirty-two minutes of contact time was required for 60 g of extract, yielding 1.7 g of purified product. Picrate paper, infra-red and 'HNMR analysis confirmed the presence and structure of linamarin. Cytotoxic effects of linamarin on MCF-7, HT-29 and HL60 cells were determined using the MTT assay. Cytotoxic effects were significantly increased in the presence of linamarase (P-glucosidase), with a 10-fold decrease in the IC50 values obtained for HL-60 cells. This study thus describes a method for the isolation and purification of linamarin from cassava, as well as its cytotoxicity potential.