The fatty acid synthase inhibitor triclosan : repurposing an anti-microbial agent for targeting prostate cancer

Inhibition of FASN has emerged as a promising therapeutic target in cancer, and numerous inhibitors have been investigated. However, severe pharmacological limitations have challenged their clinical testing. The synthetic FASN inhibitor triclosan, which was initially developed as a topical antibacterial agent, is merely affected by these pharmacological limitations. Yet, little is known about its mechanism in inhibiting the growth of cancer cells. Here we compared the cellular and molecular effects of triclosan in a panel of eight malignant and non-malignant prostate cell lines to the well-known FASN inhibitors C75 and orlistat, which target different partial catalytic activities of FASN. Triclosan displayed a superior cytotoxic profile with a several-fold lower IC50 than C75 or orlistat. Structure-function analysis revealed that alcohol functionality of the parent phenol is critical for inhibitory action. Rescue experiments confirmed that end product starvation was a major cause of cytotoxicity. Importantly, triclosan, C75 and orlistat induced distinct changes to morphology, cell cycle, lipid content and the expression of key enzymes of lipid metabolism, demonstrating that inhibition of different partial catalytic activities of FASN activates different metabolic pathways. These finding combined with its well-documented pharmacological safety profile make triclosan a promising drug candidate for the treatment of prostate cancer.

Synthesis, electron microscopy and anti-microbial properties of Fe3O4-Ag nanotubes

Electrodeposition was used for synthesizing 200 nm diameter Fe3O4-Ag nanotubes. Compositional analysis at the single nanotube level revealed a fairly uniform distribution of component elements in the nanotube microstructure. As-synthesized Fe3O4-Ag nanotubes were superparamagnetic in nature. Electron diffraction revealed the ultrafine nanocrystalline microstructure of the nanotubes. The effect of Ag on the anti-microbial response of the nanotubes was investigated by comparing the effect of sulphate reducing bacteria (SRB) on Fe3O4-Ag and Fe3O4 nanotubes. Fe3O4 nanotubes were also electro-deposited in the present study. It was observed that the Fe3O4-Ag nanotubes exhibited good resistance to sulphate reducing bacteria which revealed the anti-microbial nature of the Fe3O4-Ag nanotubes.

Anti-corrosive and anti-microbial properties of nanocrystalline Ni-Ag coatings

Anti-corrosive and anti-bacterial properties of electrodeposited nanocrystalline Ni-Ag coatings are illustrated. Pure Ni, Ni-7 at.% Ag, & Ni-14 at.% Ag coatings were electrodeposited on Cu substrate. Coating consisted of Ni-rich and Ag-rich solid solution phases. With increase in the Ag content, the corrosion resistance of the Ni-Ag coating initially increased and then decreased. The initial increase was due to the Ni-Ag solid solution. The subsequent decrease was due to the increased galvanic coupling between the Ag-rich and Ni-rich phases. For all Ag contents, the corrosion resistance of the Ni-Ag coating was higher than the pure Ni coating. Exposure to Sulphate Reducing Bacteria (SRB) revealed that the extent of bio-fouling decreased with increase in the Ag content. After 2 month exposure to SRB, the Ni-Ag coatings demonstrated less loss in corrosion resistance (58% for Ni-7 at.% Ag and 20% for Ni-14 at.% Ag) when compared pure Ni coating (115%). (C) 2016 Elsevier B.V. All rights reserved.

Anti-corrosive and anti-microbial properties of nanocrystalline Ni-Ag coatings

Anti-corrosive and anti-bacterial properties of electrodeposited nanocrystalline Ni-Ag coatings are illustrated. Pure Ni, Ni-7 at.% Ag, & Ni-14 at.% Ag coatings were electrodeposited on Cu substrate. Coating consisted of Ni-rich and Ag-rich solid solution phases. With increase in the Ag content, the corrosion resistance of the Ni-Ag coating initially increased and then decreased. The initial increase was due to the Ni-Ag solid solution. The subsequent decrease was due to the increased galvanic coupling between the Ag-rich and Ni-rich phases. For all Ag contents, the corrosion resistance of the Ni-Ag coating was higher than the pure Ni coating. Exposure to Sulphate Reducing Bacteria (SRB) revealed that the extent of bio-fouling decreased with increase in the Ag content. After 2 month exposure to SRB, the Ni-Ag coatings demonstrated less loss in corrosion resistance (58% for Ni-7 at.% Ag and 20% for Ni-14 at.% Ag) when compared pure Ni coating (115%). (C) 2016 Elsevier B.V. All rights reserved.

IQ-motif peptides as novel anti-microbial agents

The IQ-motif is an amphipathic, often positively charged, a-helical, calmodulin binding sequence found in a number of eukaryote signalling, transport and cytoskeletal proteins. They share common biophysical characteristics with established, cationic a-helical antimicrobial peptides, such as the human cathelicidin LL-37. Therefore, we tested eight peptides encoding the sequences of IQ-motifs derived from the human cytoskeletal scaffolding proteins IQGAP2 and IQGAP3. Some of these peptides were able to inhibit the growth of Escherichia coli and Staphylococcus aureus with minimal inhibitory concentrations (MIC) comparable to LL-37. In addition some IQ-motifs had activity against the fungus Candida albicans. This antimicrobial activity is combined with low haemolytic activity (comparable to, or lower than, that of LL-37). Those IQ-motifs with anti-microbial activity tended to be able to bind to lipopolysaccharide. Some of these were also able to permeabilise the cell membranes of both Gram positive and Gram negative bacteria. These results demonstrate that IQ-motifs are viable lead sequences for the identification and optimisation of novel anti-microbial peptides. Thus, further investigation of the anti-microbial properties of this diverse group of sequences is merited.

Cathelicidin-like Helminth Defence Molecules (HDMs):Absence of Cytotoxic, Anti-microbial and Anti-protozoan Activities Imply a Specific Adaptation to Immune Modulation

Host defence peptides (HDPs) are expressed throughout the animal and plant kingdoms. They have multifunctional roles in the defence against infectious agents of mammals, possessing both bactericidal and immune-modulatory activities. We have identified a novel family of molecules secreted by helminth parasites (helminth defence molecules; HDMs) that exhibit similar structural and biochemical characteristics to the HDPs. Here, we have analyzed the functional activities of four HDMs derived from Schistosoma mansoni and Fasciola hepatica and compared them to human, mouse, bovine and sheep HDPs. Unlike the mammalian HDPs the helminth-derived HDMs show no antimicrobial activity and are non-cytotoxic to mammalian cells (macrophages and red blood cells). However, both the mammalian- and helminth-derived peptides suppress the activation of macrophages by microbial stimuli and alter the response of B cells to cytokine stimulation. Therefore, we hypothesise that HDMs represent a novel family of HDPs that evolved to regulate the immune responses of their mammalian hosts by retaining potent immune modulatory properties without causing deleterious cytotoxic effects.

(1)H, (15)N and (13)C assignments of the Rhipicephalus (Boophilus) microplus anti-microbial peptide microplusin

Microplusin, a Rhipicephalus (Boophilus) microplus anti-microbial peptide (AMP) is the first member of a new family of cysteine-rich AMPs with histidine-rich regions at the N- and C-termini, which is being fully characterized by biophysical and biochemical methods. Here we report the NMR resonance assignments for (1)H, (15)N, and (13)C nuclei in the backbone and side chains of the microplusin as basis for further studies of structure, backbone dynamics and interactions mapping.

Recent advances of metal binding protein lactoferrin as an anti-microbial agent

Lactoferrin (Lf) is present in milk and gland secretions and serve as an antimicrobial function. Insufficient amounts of Lf in some secretions also appear to correlate with certain health problems. Protection against gastroenteritis is the most likely biologically relevant activity of lactoferrin. Multiple in vitro and animal studies have shown a protective effect of lactoferrin on infections with enteric microorganisms, including rotavirus, Giardia, Shigella, Salmonella and the diarrheagenic Escherichia coli. Lactoferrin has two major effects on enteric pathogens: it inhibits growth and it impairs function of surface expressed virulence factors thereby decreasing their ability to adhere or to invade mammalian cells. Lf also inhibits several species of fungi and certain parasites. This review covers the role of Lf in clearing the parasitic infections. The mechanism by which lactoferrin inhibits some parasites may be via stimulation of the process of phagocytosis, whereby immune cells engulf and digest foreign organisms. Trichomonas vaginalis is a protozoan responsible for the number one, non-viral sexually transmitted disease. In this review, we also discussed the role of Lf in cervical infections.

Drug release rate and anti-microbial effect of controlled-diffusion biopolymer membranes

In this study, a series of fibrous membranes made from cellulose acetate (CA) and polyester urethane (PEU) by co-electrospining or blend-electrospining were evaluated for drug release kinetics, in vitro anti-microbial activity and in vivo would healing performance when used as wound dressings. To stop common clinical infections, an antibacterial agent, Polyhexamethylene Biguanide (PHMB) was incorporated into e-spun fibres. The presence of CA in the wound healing membrane was found to improve hydrophilicity and permeability to air and moisture. The in vivo tests indicated that the addition of PHMB and CA considerably improved the wound healing efficiency. CA fibres became slightly swollen upon contacting with the wound exudates. It can not only speed up the liquid evaporation but also create a moisture environment for wound recovery. The drug release dynamics of membranes was controlled by the structure of membranes and component rations within membranes. The lower ration of CA:PEU retained the sound mechanical properties of membranes, and also reduced the boost release effectively and slowed down diffusion of antibacterial agent during in vitro tests. The controlled-diffusion membranes exert long-term anti-infective effect.

Anti-microbial activities of novel nanoformulated lactoferrin through oral administration

A biomolecular delivery system consisting of a novel alginate enclosed, chitosan coated ceramic antimicrobial nanocarrier containing lactoferrin (AEC-CP-Fe-bLf) and development of this multifunctional bovine iron saturated lactoferrin nanotechnology based drug delivery systems for finding treatment to parasitic and bacterial diseases was prepared. Since lactoferrin is a naturally occurring molecule its clinical application would be welcome.

Towards integrated anti-microbial capabilities: Novel bio-fouling resistant membranes by high velocity embedment of silver particles

Biofilm formation on membranes during water desalination operation and pre-treatments limits performance and causes premature membrane degradation. Here, we apply a novel surface modification technique to incorporate anti-microbial metal particles into the outer layer of four types of commercial polymeric membranes by cold spray. The particles are anchored on the membrane surface by partial embedment within the polymer matrix. Although clear differences in particle surface loadings and response to the cold spray were shown by SEM, the hybrid micro-filtration and ultra-filtration membranes were found to exhibit excellent anti-bacterial properties. Poly(sulfone) ultra-filtration membranes were used as for cross-flow filtration of Escherichia coli bacteria solutions to investigate the impact of the cold spray on the material[U+05F3]s integrity. The membranes were characterized by SEM-EDS, FT-IR and TGA and challenged in filtration tests. No bacteria passed through the membrane and filtrate water quality was good, indicating the membranes remained intact. No intact bacteria were found on hybrid membranes, loaded with up to 15. wt% silver, indicating the treatment was lysing bacteria on contact. However, permeation of the hybrid membranes was found to be reduced compared to control non-modified poly(sulfone) membranes due to the presence of the particles across the membrane material. The implementation of cold spray technology for the modification of commercial membrane products could lead to significant operational savings in the field of desalination and water pre-treatments.

Comparative study of the clinical and anti-microbial efficacy of tongue cleaners

Candida species have frequently been isolated from the oral cavities of a variety of patients, such as elderly people, dentures users, immunocompromised and health patients. Yeasts may be associated with immune response and local factors such as poor oral hygiene. It was evaluated effectiveness of tongue cleaner showing which types would be preferred by patients, changes in tongue coating and in saliva yeasts counting. Thirty patients were selected and randomly distributed into three groups. This crossover blind study evaluated the effect of tongue cleaning using: a plastic and a steel tongue scraper and a nylon soft-bristle toothbrush. All patients were instructed to use the cleaners twice a day for one week (fifteen-day wash-out period). Saliva and tongue coating samples were collected from each patient from each test period, the yeasts were counted by colony forming units per mL (CFU/ mL) and the species were identified. The patients were questioned about cleaner preference. An increase in the percentage of patients with no tongue coating after scraping was observed. A reduction in the mean number of Candida species in tongue coating was observed only after nylon soft-bristle toothbrush cleaner. Candida albicans was the prevalent species. Volunteers preferred to the steel tongue scraper (60%). Tongue cleaners reduced the tongue coating and the mean number of saliva's yeasts. Degree of tongue coating favors the Candida species colonization.

A differential concentration-dependent effect of IVIg on neutrophil functions: relevance for anti-microbial and anti-inflammatory mechanisms

Background Polymorphonuclear neutrophils (PMN) play a key role in host defences against invading microorganisms but can also potentiate detrimental inflammatory reactions in case of excessive or misdirected responses. Intravenous immunoglobulins (IVIg) are used to treat patients with immune deficiencies and, at higher doses, in autoimmune, allergic and systemic inflammatory disorders. Methodology/Principal Findings We used flow cytometry to examine the effects of IVIg on PMN functions and survival, using whole-blood conditions in order to avoid artifacts due to isolation procedures. IVIg at low concentrations induced PMN activation, as reflected by decreased L-selectin and increased CD11b expression at the PMN surface, oxidative burst enhancement, and prolonged cell survival. In contrast, IVIg at higher concentrations inhibited LPS-induced CD11b degranulation and oxidative burst priming, and counteracted LPS-induced PMN lifespan prolongation. Conclusions/Significance IVIg appears to have differential, concentration-dependent effects on PMN, possibly supporting the use of IVIg as either an anti-microbial or an anti-inflammatory agent.