RESUMEN

Some naturally occurring compounds, known for their antimicrobial activities, have been employed as food additives. However, their efficacy in treating infections caused by antibiotic-resistant bacteria is yet to be fully explored. Rapidly growing mycobacteria (RGM), a category within nontuberculous mycobacteria (NTM), are prevalent in various environments and can lead to infections in humans. The rise of antimicrobial resistance within RGM is a documented concern. In this study, we reported that four specific natural compounds effectively inhibited the growth and biofilm formation of three key RGM pathogens M. abscessus, M. fortuitum, and M. chelonae. We screened 12 natural compounds for their effectiveness against antibiotic-resistant clinical strains of RGM. Four compounds showed significant inhibitory effects from the most effective to least: trans-cinnamaldehyde, carvacrol, gentisaldehyde, and phloroglucinaldehyde. In the analysis of time-killing kinetics, gentisaldehyde and phloroglucinaldehyde displayed bactericidal activity while trans-cinnamaldehyde and carvacrol exhibited bacteriostatic effects. At 1× minimal inhibition concentrations, these compounds significantly reduced biofilm formation in all three RGM species to levels between 2.9% and 20.5% relative to controls. Checkerboard assays indicated synergistic interactions between these four compounds and antibiotics such as amikacin, clarithromycin, and linezolid. Of these 12 compound-antibiotic combinations, the pairs of carvacrol-linezolid, carvacrol-amikacin, and gentisaldehyde-clarithromycin demonstrated the most synergy against multiple RGM strains. Moreover, two other compounds citral and geraniol showed synergism with all three test antibiotics. Time-killing assays further confirmed most of synergistic combinations identified in the checkerboard tests. Our research suggests the potential of these essential oils and phenolic aldehydes, both individually and in combination with antibiotics, in treating RGM infections. In addition, this work illuminates applications of these natural compounds in environmental remediation to mitigate bacterial persistence for the control of infectious diseases. IMPORTANCE: The emergence of antimicrobial resistance within rapidly growing mycobacteria (RGM) poses a significant threat to public health. This study investigates the potential of naturally occurring compounds to combat infections caused by antibiotic-resistant RGM including M. abscessus, M. fortuitum, and M. chelonae. We identified four specific natural compounds showing impressive inhibitory effects against antibiotic-resistant clinical strains. These compounds not only inhibited the growth and biofilm formation but also exhibited synergistic interactions with antibiotics against key RGM pathogens. Our findings highlight the alternative treatment strategies for RGM infections and potential environmental applications of these natural compounds in mitigating microbial persistence and controlling infectious diseases.

RESUMEN

The use of phytochemicals for purpose of cancer therapy has been accelerated due to resistance of tumor cells to conventional chemotherapy drugs and therefore, monotherapy does not cause significant improvement in the prognosis and survival of patients. Therefore, administration of natural products alone or in combination with chemotherapy drugs due to various mechanisms of action has been suggested. However, cancer therapy using phytochemicals requires more attention because of poor bioavailability of compounds and lack of specific accumulation at tumor site. Hence, nanocarriers for specific delivery of phytochemicals in tumor therapy has been suggested. The pharmacokinetic profile of natural products and their therapeutic indices can be improved. The nanocarriers can improve potential of natural products in crossing over BBB and also, promote internalization in cancer cells through endocytosis. Moreover, (nano)platforms can deliver both natural and synthetic anti-cancer drugs in combination cancer therapy. The surface functionalization of nanostructures with ligands improves ability in internalization in tumor cells and improving cytotoxicity of natural compounds. Interestingly, stimuli-responsive nanostructures that respond to endogenous and exogenous stimuli have been employed for delivery of natural compounds in cancer therapy. The decrease in pH in tumor microenvironment causes degradation of bonds in nanostructures to release cargo and when changes in GSH levels occur, it also mediates drug release from nanocarriers. Moreover, enzymes in the tumor microenvironment such as MMP-2 can mediate drug release from nanocarriers and more progresses in targeted drug delivery obtained by application of nanoparticles that are responsive to exogenous stimulus including light.

Asunto(s)

RESUMEN

Members of the phylum Actinomycetota (formerly Actinobacteria) have historically been the most prolific providers of small bioactive molecules. Although the genus Streptomyces is the best-known member for this issue, other genera, such as Gordonia, have shown interesting potential in their specialized metabolism. Thus, we combined herein the result of a comprehensive literature survey on metabolites derived from Gordonia strains with a comparative genomic analysis to examine the potential of the specialized metabolism of the genus Gordonia. Thirty Gordonia-derived compounds of different classes were gathered (i.e., alkaloids, amides, phenylpropanoids, and terpenoids), exhibiting antimicrobial and cytotoxic activities, and several were also isolated from Streptomyces (e.g., actinomycin, nocardamin, diolmycin A1). With the genome data, we estimated an open pan-genome of 57,901 genes, most of them being part of the cloud genome. Regarding the BGCs content, 531 clusters were found, including Terpenes, RiPP-like, and NRPS clusters as the most frequent clusters. Our findings demonstrated that Gordonia is a poorly studied genus in terms of its specialized metabolism production and potential applications. Nevertheless, given their BGCs content, Gordonia spp. are a valuable biological resource that could expand the chemical spectrum of the phylum Actinomycetota, involving novel BGCs for inspiring innovative outlines for synthetic biology and further use in biotechnological initiatives. Therefore, further studies and more efforts should be made to explore different environments and evaluate other bioactivities.

RESUMEN

Nrf2 (nuclear factor erythroid 2-related factor 2) and NF-κB (nuclear factor-kappa B) signaling pathways play a central role in suppressing or inducing inflammation and angiogenesis processes. Therefore, they are involved in many steps of carcinogenesis through cooperation with multiple signaling molecules and pathways. Targeting both transcription factors simultaneously may be considered an equally important strategy for cancer chemoprevention and therapy. Several hundreds of phytochemicals, mainly edible plant and vegetable components, were shown to activate Nrf2 and mediate antioxidant response. A similar number of phytochemicals was revealed to affect NF-κB. While activation of Nrf2 and inhibition of NF-κB may protect normal cells against cancer initiation and promotion, enhanced expression and activation in cancer cells may lead to resistance to conventional chemo- or radiotherapy. Most phytochemicals, through different mechanisms, activate Nrf2, but others, such as luteolin, can act as inhibitors of both Nrf2 and NF-κB. Despite many experimental data confirming the above mechanisms currently, limited evidence exists demonstrating such activity in humans. Combinations of phytochemicals resembling that in a natural food matrix but allowing higher concentrations may improve their modulating effect on Nrf2 and NF-κB and ultimately cancer prevention and therapy. This review presents the current knowledge on the effect of selected phytochemicals and their combinations on Nrf2 and NF-κB activities in the above context.

Asunto(s)

RESUMEN

In recent years, the demand for novel antifungal therapies has increased several- folds due to its potential to treat severe biofilm-associated infections. Biofilms are made by the sessile microorganisms attached to the abiotic or biotic surfaces, enclosed in a matrix of exopolymeric substances. This results in new phenotypic characteristics and intrinsic resistance from both host immune response and antimicrobial drugs. Candida albicans biofilm is a complex association of hyphal cells that are associated with both abiotic and animal tissues. It is an invasive fungal infection and acts as an important virulent factor. The challenges linked with biofilm-associated diseases have urged scientists to uncover the factors responsible for the formation and maturation of biofilm. Several strategies have been developed that could be adopted to eradicate biofilm-associated infections. This article presents an overview of the role of C. albicans biofilm in its pathogenicity, challenges it poses and threats associated with its formation. Further, it discusses strategies that are currently available or under development targeting prostaglandins, quorum-sensing, changing surface properties of biomedical devices, natural scaffolds, and small molecule-based chemical approaches to combat the threat of C. albicans biofilm. This review also highlights the recent developments in finding ways to increase the penetration of drugs into the extracellular matrix of biofilm using different nanomaterials against C. albicans.

RESUMEN

The significant improvement of quality of life achieved over the last decades has stimulated the development of new approaches in medicine to take into account the personal needs of each patient. Precision medicine, providing healthcare customization, opens new horizons in the diagnosis, treatment and prevention of numerous diseases. As a consequence, there is a growing demand for novel analytical devices and methods capable of addressing the challenges of precision medicine. For example, various types of sensors or their arrays are highly suitable for simultaneous monitoring of multiple analytes in complex biological media in order to obtain more information about the health status of a patient or to follow the treatment process. Besides, the development of sustainable sensors based on natural chemicals allows reducing their environmental impact. This review is concerned with the application of such analytical platforms in various areas of medicine: analysis of body fluids, wearable sensors, drug manufacturing and screening. The importance and role of naturally-occurring compounds in the development of electrochemical multisensor systems and arrays are discussed.

Asunto(s)

RESUMEN

LC-MS/MS is the mainstream technique for the analysis of naturally occurring compounds in food. Because of the complex chemical composition of food, the most challenging validation parameters are those related to the matrix - linearity (calibration) and trueness. The influence of the interfering compounds on the analytical results is reflected in the extraction efficiency and matrix effect. These effects must be compensated for, if they cannot be removed or reduced by optimizing the extraction and the LC-MS/MS method. The calibration strategy is selected on the basis of the analytical conditions - complexity of matrix, and chemical structure and number of analytes. It is advisable to estimate trueness - both extraction efficacy and matrix effect during the preliminary experiments in order to select the right type of calibration. Finally, it is essential to describe the validation procedure in detail and refer to the used guidelines in order to provide a reproducible method.

Asunto(s)

RESUMEN

Macrophages, as crucial cellular components of innate immunity, are characterized by possessing high plasticity and an abnormal ability to differentiate in response to numerous stimuli. Given this, macrophages show extreme heterogeneity under both physiological and pathological conditions. Typically, macrophages can be polarized into classically activated macrophages (M1) and alternatively activated macrophages (M2) depending on their environment. The relative functions of these two subtypes are almost exactly opposed to one another. Recent studies have suggested that some naturally occurring compounds can exert regulatory effects on the progression of macrophage polarization, which implies that they could be promising therapeutic tools to treat relevant diseases. Therefore, in our current review, we summarize recent studies on several naturally occurring compounds that may possess the ability to regulate macrophage polarization and explore the associated molecular mechanisms.

Asunto(s)

RESUMEN

In this work, naturally occurring compounds, such as Vitamin E (VE) and Ferulic Acid (FA), at high concentrations, have been considered as pro-degradant agents for Low Density Polyethylene (PE). However, all obtained results using the naturally occurring molecules as pro-oxidant agents for PE have been compared with the results achieved using a classical pro-oxidant agent, such as calcium stearate (Ca stearate) and with neat PE. The preliminary characterization, through rheological, mechanical and thermal analysis, of the PE-based systems highlights that the used naturally occurring molecules are able to exert a slight plasticizing action on PE and subsequently the PE rigidity and crystallinity slightly decrease, while the ductility increases. To assess the pro-degradant activity of the considered naturally occurring compounds, thin films of neat PE and PE-based systems containing 2 and 3 wt.% Ca stearate, VE and FA have been produced and subjected to accelerated weathering upon UVB light exposure. All obtained results point out that the VE and FA, at these high concentrations, exert a clear pro-oxidant activity in PE and this pro-oxidant activity is very similar to that exerted by Ca stearate. Moreover, the VE and FA at high concentrations can be considered as suitable eco-friendly pro-degradant additives for PE, also in order to control the polyolefin degradation times.

RESUMEN

Differentiation of cancer cells entails the reversion of phenotype from malignant to the original. The conversion to cell type characteristic for another tissue is named transdifferentiation. Differentiation/transdifferentiation of malignant cells in high grade tumor mass could serve as a nonaggressive approach that potentially limits tumor progression and augments chemosensitivity. While this therapeutic strategy is already being used for treatment of hematological cancers, its feasibility for solid malignancies is still debated. We will presently discuss the natural compounds that show these properties, with focus on anthraquinones from Aloe vera, Senna, Rheum sp. and hop derived prenylflavonoids.

Asunto(s)

RESUMEN

The ubiquitous compound 4-hydroxy-3-methoxycinnamic acid, also known as ferulic acid (FA), constitutes a bioactive ingredient of many foods that may offer beneficial effects against disorders related to oxidative stress, including cancer, diabetes, and neurodegenerative diseases. This review discusses the antioxidant properties of FA, establishing relationships to several biological activities already described for this natural product. Next, 387 naturally occurring compounds, all isolated from plants and published between 1990 and 2015, the structures of which bear 1 or more feruloyl moieties, are covered in this review along with their structural formulas, botanical sources, and bioactivities. The compounds' distribution, structural patterns, bioactivities, and perspectives on food research are also succinctly discussed.

RESUMEN

This paper reports a method for evaluating antioxidant capacity based on the inhibitory effects of a macrocyclic Ni(II) complex-catalysed Briggs-Rauscher reaction. The macrocyclic Ni(II) complex NiL(ClO4)2, in which L is 5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradeca-4,11-diene, is a porphyrin-like compound, the structure of which can be found in certain enzymes. The experiments indicated that three natural compounds could temporarily quench the oscillations for a period of time prior to regeneration of oscillations. The inhibition time was related to the compound type and concentration; thus, procedures for evaluating the antioxidant activities of polyphenolic compounds were successfully established. Three polyphenolic compounds were tested to evaluate their antioxidant activities: protocatechuic acid, rutin hydrate and procyanidin. Of these three naturally occurring compounds, procyanidin was found to be the most efficient antioxidant. We have also discussed the reaction of the antioxidant with the hydroperoxyl radical (HOO) present in the oscillating system.

Asunto(s)