A small library of
phorbol 12,13-diesters bearing low lipophilicity
ester chains was prepared as potential neurogenic agents in the adult
brain. They were also used in a targeted UHPLC–HRMS screening
of the latex of Euphorbia resinifera. Two new 12-deoxy-16-hydroxyphorbol 13,16-diesters were isolated,
and their structures were deduced using two-dimensional NMR spectroscopy
and NOE experiments. The ability of natural and synthetic compounds
to stimulate transforming growth factor alpha (TFGα) release,
to increase neural progenitor cell proliferation, and to stimulate
neurogenesis was evaluated. All compounds that facilitated TGFα
release promoted neural progenitor cell proliferation. The presence
of two acyloxy moieties on the tigliane skeleton led to higher levels
of activity, which decreased when a free hydroxyl group was at C-12.
Remarkably, the compound bearing isobutyryloxy groups was the most
potent on the TGFα assay and at inducing neural progenitor cell
proliferation in vitro, also leading to enhanced
neurogenesis in vivo when administered intranasally
to mice.
Lathyrane diterpenoids are one of the primary types of secondary metabolites present in the genus Euphorbia and one of the largest groups of diterpenes. They are characterized by having a highly oxygenated tricyclic system of 5, 11 and 3 members. These natural products and some synthetic derivatives have shown numerous interesting biological activities with clinical potential against various diseases, such as cytotoxic activity against cancer cell lines, multi-drug resistance reversal, antiviral properties, anti-inflammatory activity and their capability to induce proliferation or differentiation into neurons of neural progenitor cells. The structure of the lathyrane skeleton could be considered privileged because its framework is able to direct functional groups in a well-defined space. The favorable arrangement of these makes interaction possible with more than one target. This review aims to highlight the evidence of lathyranes as privileged structures in medicinal chemistry. Chemical structures of bioactive compounds, the evaluation of biological properties of natural and semisynthetic derivatives, and the exploration of the mechanisms of action as well as target identification and some aspects of their targeted delivery are discussed.
Los microorganismos, especialmente las bacterias, están distribuidos por todo el mundo, desde el suelo, los mares y los ríos hasta el sistema digestivo de los animales y los seres humanos; por lo tanto, las bacterias mantienen una interacción constante con los compuestos utilizados por los seres humanos y los animales como los antibióticos, y con otros microorganismos que pueden ser de la misma especie o de diferentes géneros taxonómicos; esta interacción podría dar lugar a una presión selectiva sobre las bacterias en el medio ambiente y promover el intercambio genético, lo que llevaría a una propagación global de la resistencia a los antibióticos y a una afectación mundial de la salud. En este contexto, la presente revisión tiene por objeto ofrecer una visión general del rol de los seres humanos, los animales y el medio ambiente en la resistencia bacteriana, con énfasis en los procesos en el suelo y los medios acuáticos y los efectos sobre la salud humana.
Neuropathological aging is associated with memory impairment and cognitive decline, and affects several brain areas including the neurogenic niche of the dentate gyrus of the hippocampus (DG). In the healthy brain homeostatic mechanisms regulate neurogenesis in the DG to facilitate the continuous generation of neurons from neural stem cells (NSC). Nevertheless, aging reduces the number of activated neural stem cells, and diminishes the number of newly generated neurons. Strategies that promote neurogenesis in the DG may improve cognitive performance in the elderly resulting in the development of treatments to prevent the progression of neurological disorders in the aged population. Our work is aimed to discover targeting molecules to be used in the design of pharmacological agents to prevent the neurological effects of pathological aging. We study the effect of age on hippocampal neurogenesis using the SAMP8 mouse as a model of pathological aging. Thus, we show that in six-month-old SAMP8 mice, episodic and spatial memory are impaired, concomitantly the generation of neuroblasts and neurons is reduced and the generation of astrocytes is increased in this model. The novelty of our work resides in the fact that treatment of SAMP8 mice with a TGF-alpha targeting molecule, prevents the observed defects, positively regulating neurogenesis and improving cognitive performance. This compound facilitates the release of TGF-alpha in vitro and in vivo and activates signaling pathways initiated by this growth factor. We conclude that targeting the release of TGF-alpha may be the basis of pharmacological drugs to counteract the neurological effects of pathological aging.
Neuropathological aging is associated with memory impairment and cognitive decline, affecting several brain areas including the neurogenic niche of the dentate gyrus of the hippocampus (DG). In the healthy brain, homeostatic mechanisms regulate neurogenesis within the DG to facilitate the continuous generation of neurons from neural stem cells (NSC). Nevertheless, aging reduces the number of activated neural stem cells and diminishes the number of newly generated neurons. Strategies that promote neurogenesis in the DG may improve cognitive performance in the elderly resulting in the development of treatments to prevent the progression of neurological disorders in the aged population. Our work is aimed at discovering targeting molecules to be used in the design of pharmacological agents that prevent the neurological effects of brain aging. We study the effect of age on hippocampal neurogenesis using the SAMP8 mouse as a model of neuropathological aging. We show that in 6‐month‐old SAMP8 mice, episodic and spatial memory are impaired; concomitantly, the generation of neuroblasts and neurons is reduced and the generation of astrocytes is increased in this model. The novelty of our work resides in the fact that treatment of SAMP8 mice with a transforming growth factor‐alpha (TGFα) targeting molecule prevents the observed defects, positively regulating neurogenesis and improving cognitive performance. This compound facilitates the release of TGFα in vitro and in vivo and activates signaling pathways initiated by this growth factor. We conclude that compounds of this kind that stimulate neurogenesis may be useful to counteract the neurological effects of pathological aging.
Potato (Solanum tuberosum) as a food source and culinary ingredient varies is the fourth most produced noncereal crop in the world. Among multiple biotic stresses, late blight caused by Phytophthora infestans is the most destructive disease. Control of this pathogen is usually by the synthetic fungicides which have been fueled by the public concern about toxicity and environmental impact and development of pathogens resistance. Biological control agents (BCAs) seems the potentially alternative to these pesticides, biological disease control is now recognized and constitute an important tool in integrated pest management. BCAs strains should be able to protect the host plant from pathogens and fulfill the requirement for strong colonization. Bacteria such as Bacillus, Pseudomonas and Streptomyces and fungi such as Trichoderma and Penicillium were the most reported as a BCA against P. infestans using different direct antagonistic mode on the pathogen (via e.g. parasitism, antibiosis, or competition) or via exerting their biocontrol activity indirectly by induction in the plant of an induced systemic resistance to the pathogen. In this study, we present an overview and discussion of the use of beneficial microbes (bacteria and fungi) as novel BCAs for biocontrol of P. infestans.
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