A Review on Microbial Products and Their Perspective Application as Antimicrobial Agents.

Microorganisms including actinomycetes, archaea, bacteria, fungi, yeast, and microalgae are an auspicious source of vital bioactive compounds. In this review, the existing research regarding antimicrobial molecules from microorganisms is summarized. The potential antimicrobial compounds from actinomycetes, particularly Streptomyces spp.; archaea; fungi including endophytic, filamentous, and marine-derived fungi, mushroom; and microalgae are briefly described. Furthermore, this review briefly summarizes bacteriocins, halocins, sulfolobicin, etc., that target multiple-drug resistant pathogens and considers next-generation antibiotics. This review highlights the possibility of using microorganisms as an antimicrobial resource for biotechnological, nutraceutical, and pharmaceutical applications. However, more investigations are required to isolate, separate, purify, and characterize these bioactive compounds and transfer these primary drugs into clinically approved antibiotics.

Protein biomarker elucidation for the verification of biological agents in the taxonomic group of Gammaproteobacteria using tandem mass spectrometry.

Some pathogenic microbes can be used for nefarious applications and instigate population-based fear. In a bio-threat scenario, rapid and accurate methods to detect biological agents in a wide range of complex environmental and clinical matrices, is of paramount importance for the implementation of mitigation protocols and medical countermeasures. This study describes targeted and shot-gun tandem MS based approaches for the verification of biological agents from the environmental samples. The marker proteins and peptides were elucidated by an exhaustive literature mining, in silico analysis of prioritized proteins, and MS/MS analysis of abundant proteins from selected bacterial species. For the shot-gun methodology, tandem MS analysis of abundant peptides was carried from spiked samples. The validation experiments employing a combination of shot-gun tandem MS analysis and a targeted search reported here is a proof of concept to show the applicability of the methodology for the unambiguous verification of biological agents at sub-species level, even with limited fractionation of crude protein extracts from environmental samples.

UPLC-MS/MS Identification and Quantification of Withanolides from Six Parts of the Medicinal Plant Datura Metel L.

Withanolides from six parts (flower, leaf, stem, root, seed, and peel) of Datura metel L. (D metel L.) obtained from ten production areas in China were identified and quantified by UPLC-MS/MS. A total of 85 withanolides were characterized for the first time using the UPLC-Q-TOF-MS/MS system. Additionally, a simultaneous, rapid and accurate measurement method was developed for the determination of 22 bioactive withanolides from ten production areas with the UPLC-Q-TRAP-MS/MS system. The results show the total withanolide content is highest in the leaves (155640.0 ng/g) and lowest in the roots (14839.8 ng/g). Compared with other production areas, the total content of plants from Dujiangyan was the highest at 82013.9 ng/g (value range of ten areas: 82013.9-42278.5 ng/g). The results also show significant differences in the distribution of withanolides in the different plant parts, as well as across different production areas. This is a breakthrough report providing a simultaneous qualitative and quantitative analysis of 22 withanolides in D. metel L. It could be the basis for the more rational use of various parts of D. metel L., and the expansion of medicinal resources. This work also lays a solid foundation for research on the quality control of D. metel L.

Chemical-Biological Terrorism and Its Impact on Children.

Children are potential victims of chemical or biological terrorism. In recent years, children have been victims of terrorist acts such as the chemical attacks (2017-2018) in Syria. Consequently, it is necessary to prepare for and respond to the needs of children after a chemical or biological attack. A broad range of public health initiatives have occurred since the terrorist attacks of September 11, 2001. However, in many cases, these initiatives have not ensured the protection of children. Since 2001, public health preparedness has broadened to an all-hazards approach, in which response plans for terrorism are blended with those for unintentional disasters or outbreaks (eg, natural events such as earthquakes or pandemic influenza or man-made catastrophes such as a hazardous-materials spill). In response to new principles and programs that have evolved over the last decade, this technical report supports the accompanying update of the American Academy of Pediatrics 2006 policy statement "Chemical-Biological Terrorism and its Impact on Children." The roles of the pediatrician and public health agencies continue to evolve, and only their coordinated readiness and response efforts will ensure that the medical and mental health needs of children will be met successfully. In this document, we will address chemical and biological incidents. Radiation disasters are addressed separately.

Efficacy of commercially available biological agents for the topical treatment of cervical intraepithelial neoplasia: a systematic review.

BACKGROUND: Cervical cancer is a major public health issue in the world, especially in developing countries. It can be prevented through vaccination against HPV (primary prevention) and through screening and treatment of cervical intraepithelial neoplasia (CIN) (secondary prevention). Surgical methods for treatment of CIN are linked to complications such as bleeding and adverse pregnancy outcomes. Furthermore, these methods are not generally available in resource-poor settings. Therefore, topical agents for local application on the cervix have been used since decades to overpass complications and limitations of the surgical methods. AIMS: Review of the literature on the efficacy of commercially available biological agents used for topical treatment of cervical intraepithelial neoplasia (CIN). METHODS: A systematic search through PubMed and the Cochrane database was performed up to December 2017, using the medical subheadings (MesH) for topical agent, treatment, and cervical intraepithelial neoplasia. Appropriate inclusion/exclusion criteria have been used for the selection of eligible clinical studies. Clinical studies containing a minimum of 20 women, aged 18-50 with a diagnosis of CIN 1-3, and at least a 4 weeks follow-up after the end of the topical treatment were included. RESULTS: The initial electronic database search resulted in a total of 849 articles. After screening titles and abstracts, 62 articles were selected as potential studies. Of these, six articles were included in the review after reading the full text: two were on 5-FluoroUracil, two on trans retinoic acid, one on Imiquimod, and one on Cidofovir. The reported regression/remission rates for CIN differed among studies. In CIN2 patients, the overall remission rate ranged between 43 and 93% for the active agents. CONCLUSION: Among the topical agents studied, 5-FluoroUracil showed good remission rates above 80%. Varying results seen in this review is due to the differences in quality of the design between studies. Large-scale and less biaised studies are needed to elucidate the true efficacy and safety of topical agents in the treatment of CIN.

Phytochemical evaluation, antimicrobial activity, and determination of bioactive components from leaves of Aegle marmelos.

The therapeutic value of Aegle marmelos Correa (Rutaceae), commonly known as ''Bael," has been recognized as a component of traditional medication for the treatment of various human ailments. The plant, though, being highly explored, still lacks sufficient evidences for the best variety possessing the highest degree of medicinal values. The present study is focused on phytochemical screening of aqueous and methanolic leaf extracts of 18 varieties/accessions of A. marmelos. The crude extracts of A. marmelos revealed the presence of several biologically active phytochemicals with the highest quantity of alkaloids, flavonoids, and phenols in Pant Aparna variety. The antibacterial efficacy was investigated against pathogenic bacterial strains and the highest inhibitory activity of aqueous extract was obtained against S. epidermidis, whereas methanolic extract was found to be most potent against S. aureus at 40 mg/mL concentration. However, in aqueous : ethanol, the best results were observed against E. aerogenes followed by K. pneumonia and S. epidermidis. The MIC of aqueous and methanol extract of Aegle marmelos ranged from 10 mg/mL to 40 mg/mL whereas in aqueous : ethanol it ranged between 40 mg/mL and 160 mg/mL. The GC-MS analysis revealed the presence of many bioactive compounds such as flavonoids, alcohols, aldehydes, aromatic compounds, fatty acid methyl esters, terpenoids, phenolics, and steroids that can be postulated for antibacterial activity.

Survey of systems for comparative ranking of agents that pose a bioterroristic threat.

Strong efforts are made to improve preparedness for the prevention and counteraction of possible deliberate release of highly pathogenic biological agents at national and international level. An objective risk assessment for highly pathogenic biological agents is urgently needed for the purpose of prioritizing measures, evaluating the vulnerabilities and supporting rapid decisions on a scientific base in case of an emergency. Hitherto, several differing ranking schemes were developed. In general, the purpose of such ranking schemes is a comparative classification of agents under consideration of different transmission paths as well as agents threatening human and/or animal health. The analysed prioritization methods differ from qualitative to (semi-)quantitative with each its benefits and disadvantages in preciseness of the result, complexity and duration of the assessment but also in comprehensibility. Mainly, risk was defined as the product of probability and impact. In this survey, factors frequently used for the assessment of the probability and impact of a deliberate agent release were identified. Main criteria for the probability of an application were the history of use, the accessibility of the agent and possible paths of introduction and contamination as well as the feasibility of agent production. For the estimation of the impact, mainly the agent's effects on human and/or veterinary public health, depending on the target population, were examined. This includes the morbidity and mortality rates as well as the severity of induced illness, possible measures for diagnosis, and treatment and prevention. Furthermore, the economic and socioeconomic consequences were considered. In this review, the authors give an overview on open-source publications dealing with risk ranking of biological agents by outlining the criteria that were applied for risk ranking.

Wear and abrasion resistance selection maps of biological materials.

The mechanical design of biological materials has generated widespread interest in recent years, providing many insights into their intriguing structure-property relationships. A critical characteristic of load-bearing materials, which is central to the survival of many species, is their wear and abrasion tolerance. In order to be fully functional, protective armors, dentitious structures and dynamic appendages must be able to tolerate repetitive contact loads without significant loss of materials or internal damage. However, very little is known about this tribological performance. Using a contact mechanics framework, we have constructed materials selection charts that provide general predictions about the wear performance of biological materials as a function of their fundamental mechanical properties. One key assumption in constructing these selection charts is that abrasion tolerance is governed by the first irreversible damage at the contact point. The maps were generated using comprehensive data from the literature and encompass a wide range of materials, from heavily mineralized to fully organic materials. Our analysis shows that the tolerance of biological materials against abrasion depends on contact geometry, which is ultimately correlated to environmental and selective pressures. Comparisons with experimental data from nanoindentation experiments are also drawn in order to verify our predictions. With the increasing amount of data available for biological materials also comes the challenge of selecting relevant model systems for bioinspired materials engineering. We suggest that these maps will be able to guide this selection by providing an overview of biological materials that are predicted to exhibit the best abrasion tolerance, which is of fundamental interest for a wide range of applications, for instance in restorative implants and protective devices.

Muscarine, imidazole, oxazole, and thiazole alkaloids.

A great number of structurally diverse natural products containing five-membered heterocyclic subunits, such as imidazole, oxazole, thiazole, and their saturated congeners, are abundant in nature. These naturally occurring metabolites often exhibit extensive and pharmacologically important biological activities. The latest progress in the isolation, biological activities, chemical synthetic studies, and biosynthetic pathways on these natural products is summarized in this review.

Muscarine, imidazole, oxazole and thiazole alkaloids.

Nature abounds with a great number of natural products containing five-membered heterocyclic subunits, such as imidazoles, oxazoles and thiazoles, and their corresponding saturated imidazolines, oxazolines and thiazolines. These naturally occurring metabolites often exhibit pharmacologically important biological activities. In this review, the isolation, biological activities, chemical synthetic studies, and biosynthetic pathways of these natural products are summarized.

Natural products that have been used commercially as crop protection agents.

Many compounds derived from living organisms have found a use in crop protection. These compounds have formed the basis of chemical synthesis programmes to derive new chemical products; they have been used to identify new biochemical modes of action that can be exploited by industry-led discovery programmes; some have been used as starting materials for semi-synthetic derivatives; and many have been used or continue to be used directly as crop protection agents. This review examines only those compounds derived from living organisms that are currently used as pesticides. Plant growth regulators and semiochemicals have been excluded from the review, as have living organisms that exert their effects by the production of biologically active secondary metabolites.

Biogenetic proposals and biosynthetic studies on secondary metabolites of opisthobranch molluscs.

Marine chemical diversity is generated by a large number of transformations often not noted in terrestrial counterparts. Life in the oceans differs in most respects from life on land and our knowledge of the genetics and biochemistry of marine organisms is still very limited to a small number of species. Biosynthetic studies and biogenetic speculations can therefore be crucial in predicting relevant enzymes and their encoding genes, with a view to setting the stage for rational engineering of marine natural products. A further useful outcome to the identification of biosynthetic pathways is the resulting classification of natural products, which can serve to correlate chemical diversity and biodiversity. This review summarizes the present knowledge on secondary metabolites biogenesis in marine opisthobranchs, a class of organisms that has been emerging as a prolific source of structurally diverse metabolites possessing a broad variety of biological activities.

The bacterial universal stress protein: function and regulation.

The universal stress protein A (UspA) superfamily encompasses an ancient and conserved group of proteins that are found in bacteria, Archea, fungi, flies and plants. The Escherichia coli UspA is produced in response to a large number of different environmental onslaughts and UspA is one of the most abundant proteins in growth-arrested cells. Although insights into the regulation of the E. coli uspA gene have been gained, the exact roles of the Usp proteins and Usp domains remain enigmatic; they appear, in some cases, to be linked to resistance to DNA-damaging agents and to respiratory uncouplers.

Naturally occurring aristolactams, aristolochic acids and dioxoaporphines and their biological activities.

Aristolactams, having a phenanthrene chromophore are a small group of compounds mainly found in the Aristolochiaceae together with the aristolochic acids and 4,5-dioxoaporphines. In this report, these three important classes of natural products are reviewed and classified on the basis of their oxygenation pattern. In addition the biological activities of these compounds and their general chemistry are discussed.

Estudos microbiológicos e químicos do fungo marinho Scolecobasidium arenarium / Microbiological and chemical studies of the marine fungus Scolecobasidium arenarium

A micologia marinha e uma fonte promissora para a descoberta de novas moleculas bioativas, so que muito pouco explorada. Por este motivo nos incentivamos a dar inicio ao primeiro projeto no Brasil no estudo de um fungo marinho, frente a descoberta de novos produtos naturais provenientes de fungos marinhos. Uma linhagem desconhecida de um fungo marinho, denominado SS99F-6, foi isolada de sedimentos marinhos coletados no litoral norte do Estado de Sao Paulo; Posteriormente foi identificada como sendo o fungo marinho Scolecobasidium arenarium. O fungo foi submetido a fermentacao de pequena escala, objetivando a producao de metabolitos secundarios. Os metabolitos secundarios. Os metabolitos secundarios produzidos foram isolados atraves de varias tecnicas cromatograficas, resultando em 5 moleculas. Tres moleculas foram identificadas como dicetopiperazinas, sendo: a conhecida ciclo [Pro-Val] e duas novas na literatura, a ciclo [Phe-Leu] e a ciclo [Ile-Val]. As outras duas moleculas contem compostos aromaticos, no entanto nao puderam ser caracterizadas totalmente.

Screening of natural compounds for inhibitory activity on colon cancer cell migration.

We examined the effects of 75 kinds of natural compounds, such as alkaloids, phenylpropanoids, flavonoids, steroids and terpenoids on the in vitro migration and proliferation of colon 26-L5 cells, in comparison with anti-cancer drugs used for chemotherapy. Twenty-three of the 75 compounds inhibited markedly tumor cell migration. Among the 23 compounds, evodiamine showed the most potent and selective inhibitory activity on tumor cell migration with an IC50 value of 1.25 microg/ml, which was about 20 times lower than that for tumor cell proliferation. The migratory inhibition reached about 70% at 10 microg/ml of evodiamine. On the other hand, most of anti-cancer drugs tested, except for paclitaxel, had little effect on tumor cell migration at the concentrations strongly inhibiting tumor cell proliferation. Paclitaxel suppressed tumor cell migration in a concentration-dependent manner and achieved about 70% inhibition at 10 microg/ml with a marginal effect on cell proliferation. These results suggest that evodiamine and paclitaxel may be regarded as leading compounds for anti-metastatic agents acting through the inhibition of tumor cell migration without cytotoxicity.

How many endobains are there?

Oxidative metabolism is very active in brain, where large amounts of chemical energy as ATP molecules are consumed, mostly required to maintain cellular Na+/K+ gradients through the participation of the sodium pump (Na+,K+-ATPase), whose activity is selectively and potently inhibited by the alkaloid ouabain. Na+/K+ gradients are involved in nerve impulse propagation, in neurotransmitter release and cation homeostasis in the nervous system. Likewise, enzyme activity modulation is crucial for maintaining normal blood pressure and cardiovascular contractility as well as renal sodium excretion. The present article reviews the progress in disclosing putative ouabain-like substances, examines their denomination according to different research teams, tissue or biological fluid sources, extraction and purification, assays, biological properties and chemical and biophysical features. When data is available, comparison with ouabain itself is mentioned. Likewise, their potential action in normal physiology as well as in experimental and human pathology is summarized.

Molecular descriptors for effective classification of biologically active compounds based on principal component analysis identified by a genetic algorithm.

We have evaluated combinations of 111 descriptors that were calculated from two-dimensional representations of molecules to classify 455 compounds belonging to seven biological activity classes using a method based on principal component analysis. The analysis was facilitated by application of a genetic algorithm. Using scoring functions that related the number of compounds in pure classes (i.e., compounds with the same biological activity), singletons, and mixed classes, effective descriptor sets were identified. A combination of only four molecular descriptors accounting for aromatic character, hydrogen bond acceptors, estimated polar van der Waals surface area, and a single structural key gave overall best results. At this performance level, approximately 91% of the compounds occurred in pure classes and mixed classes were absent. The results indicate that combinations of only a few critical descriptors are preferred to partition compounds according to their biological activity, at least in the test cases studied here.