Antimicrobial, antioxidant activity and phytochemical prospection of Eugenia involucrata DC. leaf extracts

The species Eugenia involucrata DC. is a plant native to Brazil and is traditionally used for intestinal problems, however, little research has documented about its biological potential and phytochemical profile. Thus, the objective of this study was to carry out preliminary phytochemical prospecting, antimicrobial and antioxidant potential of E. involucrata extracts. Using the E. involucrata leaves, aqueous and organic extracts were obtained using the following solvents (ethanol, methanol, hexane, acetone, dichloromethane and ethyl acetate). The phytochemical prospecting detected the presence of saponins, steroids, flavonoids and tannins in the extracts. Ethanolic and methanolic extracts presented antimicrobial activity for most of the bacterial strains tested, as well as for yeast Candida albicans, with concentrations between 3.12 and 50 mg/mL. The ethanolic and metanolic extract presented high free radical sequestration potential (>90%). The methanol extract showed an IC50 value statistically equal to that found for the commercial antioxidant BHT (p <0.05). The crude extracts obtained with ethanol and methanol were the most promising. These results suggest that methanolic, ethanolic and aqueous extracts are a promising source of natural bioactive.

Antiviral Property of the Fungal Metabolite 3-O-Methylfunicone in Bovine Herpesvirus 1 Infection

Bovine herpesvirus type-1 (BoHV-1) is a widespread pathogen that provokes infectious rhinotracheitis and polymicrobial infections in cattle, resulting in serious economic losses to the farm animal industry and trade restrictions. To date, non-toxic active drugs against BoHV-1 are not available. The exploitation of bioactive properties of microbial products is of great pharmaceutical interest. In fact, fungi are a promising source of novel drugs with a broad spectrum of activities and functions, including antiviral properties. Hence, the potential antiviral properties of 3-O-methylfunicone (OMF), a secondary metabolite produced by Talaromyces pinophilus, were evaluated on BoHV-1. In this study, during BoHV-1 infection in bovine cells (MDBK), the non-toxic concentration of 5 µM OMF considerably reduced signs of cell death and increased cell proliferation. Furthermore, OMF significantly decreased the virus titer as well as the cytopathic effect and strongly inhibited the expression of bICP0, the major regulatory protein in the BoHV-1 lytic cycle. These findings were accompanied by a considerable up-regulation in the expression of the aryl hydrocarbon receptor (AhR), a multifunctional transcription factor also linked to the host’s response to a herpesvirus infection. Overall, our results suggest that by involving AhR, OMF shows potential against a BoHV-1 infection.

Single cell mutant selection for metabolic engineering of actinomycetes

Actinomycetes are important producers of pharmaceuticals and industrial enzymes. However, wild type strains require laborious development prior to industrial usage. Here we present a generally applicable reporter-guided metabolic engineering tool based on random mutagenesis, selective pressure, and single-cell sorting. We developed fluorescence-activated cell sorting (FACS) methodology capable of reproducibly identifying high-performing individual cells from a mutant population directly from liquid cultures. Genome-mining based drug discovery is a promising source of bioactive compounds, which is complicated by the observation that target metabolic pathways may be silent under laboratory conditions. We demonstrate our technology for drug discovery by activating a silent mutaxanthene metabolic pathway in Amycolatopsis. We apply the method for industrial strain development and increase mutaxanthene yields 9-fold to 99 mg l-1 in a second round of mutant selection. Actinomycetes are an important source of catabolic enzymes, where product yields determine industrial viability. We demonstrate 5-fold yield improvement with an industrial cholesterol oxidase ChoD producer Streptomyces lavendulae to 20.4 U g-1 in three rounds. Strain development is traditionally followed by production medium optimization, which is a time-consuming multi-parameter problem that may require hard to source ingredients. Ultra-high throughput screening allowed us to circumvent medium optimization and we identified high ChoD yield production strains directly from mutant libraries grown under preset culture conditions. In summary, the ability to screen tens of millions of mutants in a single cell format offers broad applicability for metabolic engineering of actinomycetes for activation of silent metabolic pathways and to increase yields of proteins and natural products.

Biodegradation Potential of SteccherinumOchraceum: Growth on Different Wood Types and Preliminary Evaluation of Enzymatic Activities

White-rot fungi isa source of a great variety of oxidative and hydrolytic enzymes suitable for biotechnological applications, e.g. in pulp and paper, textile and food industries, bioethanol production, degradation of recalcitrant environmental pollutants,and others. Steccherinumochraceum is a xylotrophicwhite-rot basidiomycetethat can be found in variousclimatic zones on different woody substrates (mostly well decayed). For this research, seventeenstrains of S. ochraceumwere collected in different regions of Russia from various wood substrates (aspen, alder, oak, hazel, birch and willow). Phylogeneticanalyseswere performedbasedon the nucleotide sequences of ITS1, ITS2, 5.8S rRNA, 28S rRNA, β-tubulin and tef1.Oxidaseandcellulaseactivitieswereassessedbyplate-tests with ABTS and CMC. Forevaluation of biodegradation potential,solid state fermentation on alder and pine sawdust wasperformed. Weightanddensitylossaswellas the C:Nratioweremeasuredafter 90 days of cultivation.All S. ochraceum strains exhibited high oxidative activity towards ABTS, indicating secretion of oxidative enzymes (i.e. laccases and class II peroxidases). Cellulase activity was medium or low for most strains and in some strains – absent. Allstrainswereabletodegradealderandpinesawdust. There was no correlation between the enzymatic activity, biodegradation potential and geographic origin of S. ochraceum strains. However, S. ochraceum strains isolated from the same wood substrates exhibited similar characteristics in most cases. Strain LE-BIN 3398 was the most effective for degrading both alder and pine sawdust and could be regarded as a promising source of oxidative enzymes for biotechnology. Keywords: basidiomycetes, biodegradation, solid state fermentation, oxidase activity, Steccherinumochraceum

Tannins as Hemostasis Modulators

The hemostasis system is often affected by complications associated with cardiovascular diseases, which results in thromboembolic events. Compounds of plant origin and plant extracts are considered as a promising source of substances that could modulate the functioning of the hemostasis system and thus reduce the risk of thromboembolism. Among them, tannins, which are plant-origin compounds with potential effects in hemostasis, deserve a special mention. This paper describes the hemostasis-modifying ability of three groups of tannins, namely ellagitannins, gallotannins, and procyanidins. The review highlights the desirable as well as undesirable influence of tannins on specific components of hemostasis, namely platelets, coagulation system, fibrinolysis system, and endothelium, and the multidirectional effect of these compounds on the thrombotic process. Studies performed under normal and pathological conditions such as diabetes or hypercoagulation are described, and the pathophysiology-dependent action of tannins is also highlighted. Most of the studies presented in the paper were performed in vitro, and due to the low bioavailability of tannins more studies should be conducted in the future to understand their actual activity in vivo.

Mesenchymal Stem Cell Immunomodulation: A Novel Intervention Mechanism in Cardiovascular Disease

Mesenchymal stem cells (MSCs) are the member of multipotency stem cells, which possess the capacity for self-renewal and multi-directional differentiation, and have several characteristics, including multi-lineage differentiation potential and immune regulation, which make them a promising source for cell therapy in inflammation, immune diseases, and organ transplantation. In recent years, MSCs have been described as a novel therapeutic strategy for the treatment of cardiovascular diseases because they are potent modulators of immune system with the ability to modulating immune cell subsets, coordinating local and systemic innate and adaptive immune responses, thereby enabling the formation of a stable inflammatory microenvironment in damaged cardiac tissues. In this review, the immunoregulatory characteristics and potential mechanisms of MSCs are sorted out, the effect of these MSCs on immune cells is emphasized, and finally the application of this mechanism in the treatment of cardiovascular diseases is described to provide help for clinical application.

Systematic Review: microRNAs as Potential Biomarkers in Mild Cognitive Impairment Diagnosis

The rate of progression from Mild Cognitive Impairment (MCI) to Alzheimer's disease (AD) is estimated at &gt;10% per year, reaching up to 80–90% after 6 years. MCI is considered an indicator of early-stage AD. In this context, the diagnostic screening of MCI is crucial for detecting individuals at high risk of AD before they progress and manifest further severe symptoms. Typically, MCI has been determined using neuropsychological assessment tools such as the Montreal Cognitive Assessment (MoCA) or Mini-Mental Status Examination (MMSE). Unfortunately, other diagnostic methods are not available or are unable to identify MCI in its early stages. Therefore, identifying new biomarkers for MCI diagnosis and prognosis is a significant challenge. In this framework, miRNAs in serum, plasma, and other body fluids have emerged as a promising source of biomarkers for MCI and AD-related cognitive impairments. Interestingly, miRNAs can regulate several signaling pathways via multiple and diverse targets in response to pathophysiological stimuli. This systematic review aims to describe the current state of the art regarding AD-related target genes modulated by differentially expressed miRNAs in peripheral fluids samples in MCI subjects to identify potential miRNA biomarkers in the early stages of AD. We found 30 articles that described five miRNA expression profiles from peripheral fluid in MCI subjects, showing possible candidates for miRNA biomarkers that may be followed up as fluid biomarkers or therapeutic targets of early-stage AD. However, additional research is needed to validate these miRNAs and characterize the precise neuropathological mechanisms.

Profiling of Phenolic Compounds of Fruit Peels of Different Ecotype Bananas Derived from Domestic and Imported Cultivars with Different Maturity

Banana is one of the most produced and consumed fruits in the world and its fruit peel accounts for about 40% of the total fresh quantity of ripe fruit, which is usually regarded as waste and poses serious environmental hazards. However, it is a promising source of natural bioactive compounds including phenolic compounds. Determination of the phenolic compounds in fruit peel from different cultivars and subgroups over a range of maturities provides convincing information for making full use of them. This study developed a sensitive and reliable analytical method—ultra-high performance liquid chromatography—coupled with electrospray ionization tandem mass spectrometry (UPLC-MS/MS) for measuring phenolic compounds in fruit peel from different ecotype cultivars and subgroups with different maturity. The results showed that quinic acid had the highest concentration ratio among the main phenolic compounds in the green/ripe peel of all banana cultivars; among all banana cultivars, the total phenolic compound contents of green banana peel were significantly higher than that of ripe banana peel; the total phenolic compound contents in the green/ripe fruit peel of non-dessert bananas were significantly higher than that of dessert bananas (green: non-dessert banana 1.48 ± 0.44 mg/g vs. dessert banana 0.97 ± 0.12 mg/g; ripe: non-dessert banana 0.26 ± 0.13 mg/g vs. dessert banana 0.19 ± 0.06 mg/g). These data provide a basis for the rational utilization of phenolic compound extractions from banana peel with huge biomass in the next step.

A Window of Opportunity: Perilymph Sampling from the Round Window Membrane Can Advance Inner Ear Diagnostics and Therapeutics

In the clinical setting, the pathophysiology of sensorineural hearing loss is poorly defined and there are currently no diagnostic tests available to differentiate between subtypes. This often leaves patients with generalized treatment options such as steroids, hearing aids, or cochlear implantation. The gold standard for localizing disease is direct biopsy or imaging of the affected tissue; however, the inaccessibility and fragility of the cochlea make these techniques difficult. Thus, the establishment of an indirect biopsy, a sampling of inner fluids, is needed to advance inner ear diagnostics and allow for the development of novel therapeutics for inner ear disease. A promising source is perilymph, an inner ear liquid that bathes multiple structures critical to sound transduction. Intraoperative perilymph sampling via the round window membrane of the cochlea has been successfully used to profile the proteome, metabolome, and transcriptome of the inner ear and is a potential source of biomarker discovery. Despite its potential to provide insight into inner ear pathologies, human perilymph sampling continues to be controversial and is currently performed only in conjunction with a planned procedure where the inner ear is opened. Here, we review the safety of procedures in which the inner ear is opened, highlight studies where perilymph analysis has advanced our knowledge of inner ear diseases, and finally propose that perilymph sampling could be done as a stand-alone procedure, thereby advancing our ability to accurately classify sensorineural hearing loss.