Biosurfactant: green additives for the next generation pharmaceutical formulations

Synthetic Biology, a multidisciplinary field, is growing rapidly. Improving the understanding of biological systems through mimicry and producing bio-orthogonal systems with new functions are two complementary pursuits in this field. A web server called FMM (From Metabolite to Metabolite) was developed for this purpose. FMM can reconstruct metabolic pathways form one metabolite to another metabolite among different species, based mainly on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and other integrated biological databases. Novel presentation for connecting different KEGG maps is newly provided. Both local and global graphical views of the metabolic pathways are designed. FMM has many applications in Synthetic Biology and Metabolic Engineering. For example, the reconstruction of metabolic pathways to produce valuable metabolites or secondary metabolites in bacteria or yeast is a promising strategy for drug production. FMM provides a highly effective way to elucidate the genes from which species should be cloned into those microorganisms based on FMM pathway comparative analysis. Consequently, FMM is an effective tool for applications in synthetic biology to produce both drugs and biofuels. This novel and innovative resource is now freely available at http://FMM.mbc.nctu.edu.tw/.

Introduction Over the past several decades illicit stimulant (STIM) use has developed into a major, national crisis. At our urban, safety net hospital, this is evident in a consistent increase in patients with chemical evidence of methamphetamine, amphetamine and cocaine use. Adverse health consequences of STIM use are well known, however potential metabolic consequences in patients with significant burns has not been studied. Our hypothesis was that this patient population is both undernourished and hypermetabolic when compared to those who test negative for stimulants. Methods This was a retrospective chart review of burn patients over a 6-year period who suffered a burn injury ≥ 20% TBSA and had both toxicology and indirect calorimetry testing completed. Patients were stratified into 2 groups according to toxicology results, positive for stimulants and negative for stimulants. Descriptive statistics were calculated for demographic and outcome data. Results A total of 332 patients were admitted over the 6-year period with burn injuries of ≥ 20% TBSA. Among those 140 had both toxicology and indirect calorimetry testing completed. When stratified by toxicology results 34 were positive (POS) and 106 were negative (NEG). There was no significant difference between groups for age 43.21 years POS vs 47.26 years NEG, % TBSA 34% POS vs 35% NEG, or BMI 27.5 kg POS vs 29 kg NEG. Likewise, there were no significant differences in RQ, 0.94 POS vs 0.93, REE 2513 POS vs 2412 NEG or COVAR 5.87 POS vs 5.54 NEG. There was no significant difference in mortality between the two groups 12% POS vs 23% NEG (p=.220). Conclusions We were unable to reject the null hypothesis in this study. Nearly two thirds of patients admitted during the study period did not have toxicology testing done and this may have prospectively introduced a selection bias into our retrospective study. Uniformity and protocolization of toxicology testing are necessary to avoid selection bias in order to meaningfully study the potential effects of illicit drugs on the outcomes of burn patients. Applicability of Research to Practice While we were unable to demonstrate a significant impact of stimulant use on patient metabolism and nutritional status with this study, it remains our hypothesis that such a relationship exists.

Bacteria and fungi have a high potential to produce compounds that display large structural change and diversity, thus displaying an extensive range of biological activities. Secondary metabolism or specialized metabolism is a term for pathways and small molecule products of metabolism that are not mandatory for the subsistence of the organism but improve and control their phenotype. Their interesting biological activities have occasioned their application in the fields of agriculture, food, and pharmaceuticals. Metabolic engineering is a powerful approach to improve access to these treasured molecules or to rationally engineer new ones. A thorough overview of engineering methods in secondary metabolism is presented, both in heterologous and epigenetic modification. Engineering methods to modify the structure of some secondary metabolite classes in their host are also intensively assessed.

Microbial natural product drug discovery and development has entered a new era, driven by microbial genomics and synthetic biology. Genome sequencing has revealed the vast potential to produce valuable secondary metabolites in bacteria and fungi. However, many of the biosynthetic gene clusters are silent under standard fermentation conditions. By rational screening for mutations in bacterial ribosomal proteins or RNA polymerases, ribosome engineering is a versatile approach to obtain mutants with improved titers for microbial product formation or new natural products through activating silent biosynthetic gene clusters. In this review, we discuss the mechanism of ribosome engineering and its application to natural product discovery and yield improvement in Streptomyces. Our analysis suggests that ribosome engineering is a rapid and cost-effective approach and could be adapted to speed up the discovery and development of natural product drug leads in the post-genomic era.

Enzymes of the chalcone synthase (CHS) superfamily catalyze the production of a variety of secondary metabolites in bacteria, fungi and plants. Some of these metabolites have played important roles during the early evolution of land plants by providing protection from various environmental assaults including UV irradiation. The genome of the moss, Physcomitrella patens, contains at least 17 putative CHS superfamily genes. Three of these genes (PpCHS2b, PpCHS3 and PpCHS5) exist in multiple copies and all have corresponding ESTs. PpCHS11 and probably also PpCHS9 encode non-CHS enzymes, while PpCHS10 appears to be an ortholog of plant genes encoding anther-specific CHS-like enzymes. It was inferred from the genomic locations of genes comprising it that the moss CHS superfamily expanded through tandem and segmental duplication events. Inferred exon-intron architectures and results from phylogenetic analysis of representative CHS superfamily genes of P. patens and other plants showed that intron gain and loss occurred several times during evolution of this gene superfamily. A high proportion of P. patens CHS genes (7 of 14 genes for which the full sequence is known and probably 3 additional genes) are intronless, prompting speculation that CHS gene duplication via retrotransposition has occurred at least twice in the moss lineage. Analyses of sequence similarities, catalytic motifs and EST data indicated that a surprisingly large number (as many as 13) of the moss CHS superfamily genes probably encode active CHS. EST distribution data and different light responsiveness observed with selected genes provide evidence for their differential regulation. Observed diversity within the moss CHS superfamily and amenability to gene manipulation make Physcomitrella a highly suitable model system for studying expansion and functional diversification of the plant CHS superfamily of genes.

In this paper, we investigated the abilities of five sugar-based synthetic surfactants and biosurfactants from three different families (i.e., alkyl polyglycoside (APG), sophorolipid (SL), and rhamnolipid (RL)) to dissolve and mobilize non-aqueous phase liquid (NAPL) components, i.e., toluene and perchloroethylene (PCE), adsorbed on porous matrices. The objective of this study was to establish a benchmark for the selection of suitable surfactants for the flushing aquifer remediation technique. The study involved a physicochemical characterization of the surfactants to determine the critical micelle concentration (CMCs) and interfacial properties. Subsequently, a batch study, through the construction of adsorption isotherms, made it possible to evaluate the surfactants’ capacities in contaminant mobilization via the reduction of their adsorptions onto a reference adsorbent material, a pine wood biochar (PWB). The results indicate that a synthetic surfactant from the APG family with a long fatty acid chain and a di-rhamnolipid biosurfactant with a shorter hydrophobic group offered the highest efficiency values; they reduced water surface tension by up to 54.7% and 52%, respectively. These two surfactants had very low critical micelle concentrations (CMCs), 0.0071 wt% and 0.0173 wt%, respectively; this is critical from an economical point of view. The batch experiments showed that these two surfactants, at concentrations just five times their CMCs, were able to reduce the adsorption of toluene on PWB by up to 74% and 65%, and of PCE with APG and RL by up to 65% and 86%, respectively. In general, these results clearly suggest the possibility of using these two surfactants in surfactant-enhanced aquifer remediation technology.

The need to protect human and environmental health and avoid the widespread use of substances obtained from nonrenewable sources is steering research toward the discovery and development of new molecules characterized by high biocompatibility and biodegradability. Due to their very widespread use, a class of substances for which this need is particularly urgent is that of surfactants. In this respect, an attractive and promising alternative to commonly used synthetic surfactants is represented by so-called biosurfactants, amphiphiles naturally derived from microorganisms. One of the best-known families of biosurfactants is that of rhamnolipids, which are glycolipids with a headgroup formed by one or two rhamnose units. Great scientific and technological effort has been devoted to optimization of their production processes, as well as their physicochemical characterization. However, a conclusive structure–function relationship is far from being defined. In this review, we aim to move a step forward in this direction, by presenting a comprehensive and unified discussion of physicochemical properties of rhamnolipids as a function of solution conditions and rhamnolipid structure. We also discuss still unresolved issues that deserve further investigation in the future, to allow the replacement of conventional surfactants with rhamnolipids.

Standard 24‐h toxicity tests were performed to determine the acute toxicity of Bayluscide (5,2′‐dichloro‐4′‐nitrosalicylanilide) and 3‐trifluoromethyl‐4‐nitrophenol (TFM) to two strains of the oligochaete worm Tubifex tubifex exposed and unexposed to Myxobolus cerebralis, the causative agent of whirling disease. In addition, microcosm trials were conducted to test the effect of three treatment levels of each chemical on the density of T. tubifex in an earthen hatchery pond. In the toxicity tests, worms that were susceptible to M. cerebralis infection were more sensitive to both chemicals than worms that were resistant to the parasite. The toxicity differences of exposed and unexposed worms within a lineage were not as great as those between lineages. Among worms that were susceptible to M. cerebralis, the concentrations of TFM that were lethal to 50% of the test organisms (LC50s) were 6.3 mg/L for worms that had been exposed to M. cerebralis myxospores and 7.3 mg/L for unexposed worms; for resistant worms, the corresponding LC50s were 8.2 and 7.7 mg/L. Among susceptible worms, the LC50s of Bayluscide were 0.060 mg/L for organisms exposed to M. cerebralis myxospores and 0.062 mg/L for unexposed organisms; resistant worms had LC50s of 0.096 and 0.106 mg/L. In the microcosm trials, Bayluscide treatments reduced worm densities by 73–82%, while the TFM treatments reduced worm densities by 34–88%. Given its rapid degradation, relatively selective toxicity, lower cost, and regulatory status, Bayluscide appears to be the best candidate for further study as a chemical control of the oligochaete host of the parasite that causes whirling disease in salmonid fishes.

Citrate-capped silver nanoparticles (AgNP) are widely used in industry, consumer products, and medical appliances. However, information on the environmental toxicity and human health is not comprehensive. Further, the physicochemical properties of AgNP make it difficult to test toxicity, as nanosized particles, due to their size, may increase by aggregation or agglomeration in some administration vehicles. In this study, stability of AgNP was investigated in different types of isotonic solutions, which is important for in vitro testing or toxicokinetic studies using intravenous (iv) injection. Size, morphology, zeta potential, and ion formation were investigated in isotonic solutions for the physicochemical characterization of AgNP. Aggregation and precipitation of AgNP were observed in phosphate-buffered saline or 0.9% NaCl, while AgNP were stable without aggregation or precipitation in 5% glucose in isotonic solution. The average size of AgNP in 5% glucose was approximately 10 nm at different temperatures of 10, 25, or 36°C and at varying concentrations from 10 to 1000 ppm. It is noteworthy that this is almost the same size distribution as that in the water-based suspension of AgNP supplied by the manufacturer. Zeta potential ranged from –40 to –60 mV, suggesting that the repulsion forces of AgNP are not disturbed to a sufficient degree to aggregate while osmolarity is in the isotonic range of 290 ± 10 mOsm/kg in 5% glucose solution. Data suggest that AgNP in a 5% glucose solution may be used in the toxicity test via iv injection without adverse consequences in blood.

Flavonoids, a wide range of phenolic compounds produced as secondary metabolites in plants, bacteria and fungi, have highly potent activities. In this study, the fungus Gymnoascus dankaliensis was isolated in spring from sheep dung samples, and itsability to produce a secondary metabolite was investigated. The fungal secondary metabolite was extracted, and the antimicrobial and antioxidant activitis were tested. The results showed that Gymnoascusdankaliensis, thefirst ever isolated fungus from dung in Basrah, could produce a secondary metabolite that were produced using a Solid State Ferementation SSF medium after 40 days of incubation. The bioactive compounds were extracted from the solid media by using ethyl acetate. The chemical identification of the extracted bioactive compound indicated that the isolated compound belonged to the flavonoid group. The isolated flavonoid compound tested as an antimicrobial agent against three clinical isolates of bacteria,Escherichia coli , Staphylococcus aureus and and Bacillus subtilis, was also tested against two yeast isolates Candida albicans and C. tropicalis. The results recorded the largest inhibition zone in S.aureus. Whereas C.albicans was found to be more sensitive toward the isolated flavonoid compound than C. tropicalis. The antioxidant activity of the isolated compound was investigated using DPPH (1,1-diphenyl-2-picrylhydrazyl) method where it showed moderate antioxidant activity compared to ascorbic acid.

The oceans are the world’s most important sources of biological activity, water, and biomass production. They supply food, oxygen, and other natural products critical for human existence, and interactions between the oceans and the climate. The oceans serve as the world’s greatest reservoir of biodiversity, including marine mammals, fish, crustaceans, molluscs, and countless species of zoophytoplankton. The ocean is a key source of organisms that are beginning to provide new and potent drugs for the treatment of human disease, as well as new products that use in biotechnology. Ocean can support human health, through providing new sources of drugs to treat human disease. Bioactive metabolites derived from marine organisms provide a rich source of chemical diversity that can contribute to design and development of new and potentially useful pharmaceutical agents. The marine ecosystem possesses efficient pharmaceutical materials to identify, isolate and characterize new compounds suitable for therapeutic purposes. Marine sponges, tunicates, fishes, soft corals, nudibranchs, sea hares, molluscs, echinoderms, bryozoans, prawns, shells, sea slugs, and marine microorganisms are sources of bioactive compounds. The current review is designed to collate all currently available data about the marine drugs with respect to sources, classification, chemical classes, metabolites of marine algae, fungi, bacteria and invertebrates, techniques for separation and isolation, and examples. This review aims to provide a holistic, multidisciplinary account of the current state of affairs on this topic.

Inflammatory bowel disease (IBD) has gained increasing attention from researchers in terms of its pathophysiology as a global disease with a growing incidence. Although the exact etiology of IBD is still unknown currently, various studies have made us realize that it is related to the dysbiosis of intestinal microbiota and the link between the two may not just be a simple causal relationship, but also a dynamic and complicated one. The intestinal microbiota has been confirmed to be closely related to the occurrence, development, and treatment of IBD. Therefore, this review focuses on the changes in the structure, function, and metabolites of intestinal bacteria, fungi, and viruses in influencing IBD, as well as various approaches to IBD treatment by changing disordered intestinal microbiota. Ultimately, more clinical studies will be needed to focus on the efficacy of intestinal microbiota-based treatments in IBD, because of the existence of both advantages and disadvantages.

Patient Education| 2021 Use of Psychostimulant Medication: Tips for Parents—ADHD Toolkit Connected Content Translation: Consumo de medicamentos psicoestimulantes: Consejos para padres—ADHD Toolkit Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Share Icon Share Facebook Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Use of Psychostimulant Medication: Tips for Parents—ADHD Toolkit. Pediatric Patient Education 2021; 10.1542/pco_document023 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search nav search search input Search input auto suggest search filter All AAP SitesAll PublicationsPediatric Patient Education Search Advanced Search Topics: adult attention deficit hyperactivity disorder, attention-deficit/hyperactivity disorder, psychostimulant Stimulant medications are defined as controlled substances under federal and state regulations. The possession of stimulant medication without a prescription is against the law.Money does not need to be exchanged for a gift or another exchange of a controlled substance to be considered a “sale.”Appropriate treatment of ADHD does not increase the risk of developing a substance use disorder in the future. In fact, the latest evidence is that effective treatment of ADHD, including stimulant medication, actually reduces that risk. Treat your teen as an active participant in the treatment process.Talk about best medication doses, times, and delivery systems available.Include your teen in any medication discussions with the pediatrician.Keep medications in a safe, locked, and monitored location.Parents must monitor their teen’s self-administration of medication.Parents must maintain knowledge of the appropriate dose, timing, and weekend... © 2020 American Academy of Pediatrics. All rights reserved. You do not currently have access to this content.

Replacement of in vivo acute oral toxicity studies by in vitro cytotoxicity methods: Opportunities, limits and regulatory status

Respiratory distress syndrome (RDS) is a leading cause of morbidity and mortality in premature neonates. This syndrome is caused by a lack of endogenous surfactant production in the lungs. Surfactant replacement was established as a safe and effective treatment in the 1990s and has become the standard of care for these infants. Surfactant products are either protein-free synthetic phospholipid compounds or animal-derived lung preparations. Currently, about 90,000 infants a year receive treatment with one of the commercially available animal-derived surfactants. Lucinactant (Surfaxin®) is a new synthetic surfactant with a pulmonary surfactant-associated protein B mimic that recently received FDA approval. The clinical trials that have been performed, although underpowered, may indicate that lucinactant is superior to phospholipid synthetic surfactant preparations and at least as effective as animal-derived surfactants in reducing morbidity and mortality from RDS. This review summarizes the current clinical knowledge about lucinactant.