Stress is a stimulus or a succession of stimuli tending to disrupt the homeostasis of an organism. An organism is consisting of a multitude of cells that singly undergo the effects of external ...factors that disturb or upset their homeostatic regulation. Stimuli acting as potential stressors are numerous, and include physical agents (ionizing radiation), non-physiological oxygen levels (hypoxia, hyperoxia) and chemotherapeutics. Lastly, also senescence, a physiological process occurring in all organisms, can be considered as a potential stressor. The cell response to multiple oxidative stresses involves mitochondria, since these organelles represent the major source of Reactive Oxygen Species (ROS) that drive the occurrence of pathological conditions and ageing by activating specific signalling pathways. Nevertheless, under physiological conditions the cells are able to exert an antioxidant response which, controlling ROS/Reactive Nitrogen Species (RNS) homeostasis, is involved in mediating cell differentiation, proliferation and migration. Thus, this review focuses the attention to the role played by mitochondria in the physiological and non-physiological signalling responses of eukaryotic cells to some oxidative stresses, in order to identify potential therapeutic targets to counteract oxidative stress effects and mitochondrial-related pathologies.
Due to its exceptional physical properties, such as high electronic conductivity, good thermal stability, excellent mechanical strength, and chemical versatility, graphene has sparked a lot of ...interest in the scientific community for various applications. It has therefore been employed as an antibacterial agent, in photothermal therapy (PTT) and biosensors, in gene delivery systems, and in tissue engineering for regenerative purposes. Since it was first discovered in 1947, different graphene derivatives have been synthetized from pristine graphene. The most adaptable derivate is graphene oxide (GO). Owing to different functional groups, the amphiphilic structure of GO can interact with cells and exogenous or endogenous growth/differentiation factors, allowing cell adhesion, growth, and differentiation. When GO is used as a coating for scaffolds and nanomaterials, it has been found to enhance bone, chondrogenic, cardiac, neuronal, and skin regeneration. This review focuses on the applications of graphene-based materials, in particular GO, as a coating for scaffolds in bone and chondrogenic tissue engineering and summarizes the most recent findings. Moreover, novel developments on the immunomodulatory properties of GO are reported.
Like other organs, brain functions diminish with age. Furthermore, for a variety of neurological disorders-including Alzheimer's disease-age is one of the higher-risk factors. Since in many Western ...countries the average age is increasing, determining approaches for decreasing the effects of aging on brain function is taking on a new urgency. Neuroinflammation and oxidative stress are two convoluted key factors in brain aging and chronic neurodegenerative diseases. The diverseness of factors, causing an age-related decrease in brain functions, requires identifying small molecules that have multiple biological activities that can affect all these factors. One great source of these small molecules is related to polyphenolic flavonoids. Recently, 3,3',4',7-tetrahydroxyflavone (fisetin) has been reported as a potent senotherapeutic capable of extending lifespan by reducing peroxidation levels and enhancing antioxidant cell responses. The neuroprotective effects of fisetin have been shown in several in vitro and in vivo models of neurological disorders due to its actions on multiple pathways associated with different neurological disorders. The present work aims to collect the most recent achievements related to the antioxidant and neuroprotective effects of fisetin. Moreover, in silico pharmacokinetics, pharmacodynamics, and toxicity of fisetin are also comprehensively described along with emerging novel drug delivery strategies for the amelioration of this flavonol bioavailability and chemical stability.
Snail slime (SS) is a viscous secretion obtained from different snail species. SS composition is variable according to factors such as the extraction method. Even if several papers have been ...published regarding this topic, the molecular mechanisms at the base of SS biological effects remain unexplored. Thus, the aim of this study is to evaluate the capability of SS, extracted with the cruelty-free Muller method, to promote viability and angiogenesis processes and, in parallel, to counteract inflammation occurrence on skin cell populations. SS was administered to keratinocytes, macrophages and fibroblasts, then cell viability, through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, cytotoxicity by lactate dehydrogenase (LDH) assay, morphology by haematoxylin-eosin staining, gene and protein expression through real-time polymerase chain reaction (PCR) and Western blot, cell cycle phases by flow cytometry, and collagen secretion using an enzyme-linked immunosorbent assay (ELISA) test, were measured. Our results evidence SS capability to promote fibroblast viability and to trigger recovery mechanisms by activating the Erk protein. Moreover, an appreciable anti-inflammatory effect due to the significant reduction in cyclooxygenase-2 expression, and a positive modulation of new blood vessel formation demonstrated by increased Angiopoietin 1 gene expression and a higher matrix deposition (evidenced by the augmented amount of released collagen I) can be identified. This evidence led us to assume that the Muller method extracted-SS represents a valuable and promising natural product suitable for cosmetic and skin care formulations.
Bone loss raises great concern in numerous situations, such as ageing and many diseases and in both orthopedic and dentistry fields of application, with an extensive impact on health care. Therefore, ...it is crucial to understand the mechanisms and the determinants that can regulate osteogenesis and ensure bone balance. Autophagy is a well conserved lysosomal degradation pathway, which is known to be highly active during differentiation and development. This review provides a revision of the literature on all the exogen factors that can modulate osteogenesis through autophagy regulation. Metal ion exposition, mechanical stimuli, and biological factors, including hormones, nutrients, and metabolic conditions, were taken into consideration for their ability to tune osteogenic differentiation through autophagy. In addition, an exhaustive overview of biomaterials, both for orthopedic and dentistry applications, enhancing osteogenesis by modulation of the autophagic process is provided as well. Already investigated conditions regulating bone regeneration via autophagy need to be better understood for finely tailoring innovative therapeutic treatments and designing novel biomaterials.
Abstract Oxidative stress due to increased formation of reactive oxygen species (ROS) in target cells of dental resin monomers like 2-hydroxyethyl methacrylate (HEMA) is a major mechanism underlying ...the disturbance of vital cell functions including mineralization and differentiation, responses of the innate immune system, and the induction of cell death via apoptosis. Although a shift in the equilibrium between cell viability and apoptosis is related to the non-enzymatic antioxidant glutathione (GSH) in HEMA-exposed cells, the major mechanisms of adaptive antioxidant cell responses to maintain cellular redox homeostasis are still unknown. The present study provides insight into the induction of a communicating network of pathways under the control of the redox-sensitive transcription factor Nrf2, a major transcriptional activator of genes coding for enzymatic antioxidants. Here, oxidative stress was indicated by DCF fluorescence in cells after a short exposure (1 h) to HEMA, while DHR123 fluorescence significantly increased about 1.8-fold after a long exposure period (24 h) showing the formation of hydrogen peroxide (H2 O2 ). The corresponding expression of Nrf2 was activated immediately after HEMA exposure (1 h) and remained constant up to 24 h. Nrf2-regulated expression of enzymes of the glutathione metabolism (glutathione peroxidase 1/2, glutathione reductase) decreased in HEMA-exposed cells as a result of GSH depletion, and superoxide dismutase expression was downregulated after H2 O2 overproduction. However, the expression of Nrf2-controlled enzymatic antioxidants (catalase, peroxiredoxin, thioredoxin 1, thioredoxin reductase, heme oxygenase-1) and the NADPH-regenerating system (glucose 6-phosphate dehydrogenase, transaldolase) was increased. Phenolic tert - butylhydroquinone (tBHQ), a classic inducer of the Nrf2 pathway, reduced oxidative stress and protected cells from HEMA-induced cell death through a shift in the number of cells in necrosis to apoptosis. The expression of Nrf2 and related enzymatic antioxidants downstream was enhanced by tBHQ in parallel. In conclusion, this investigation expanded the detailed understanding of the underlying mechanisms of HEMA-induced oxidative stress, and highlighted the cross-talk and interdependence between various Nrf2-regulated antioxidant pathways as a major adaptive cell response. The current results demonstrate that modulation of the Nrf2-mediated cellular defense response is an effective means for manipulating the sensitivity of cells to dental resin monomers.
Many bone substitutes have been proposed for bone regeneration, and researchers have focused on the interactions occurring between grafts and host tissue, as the biologic response of host tissue is ...related to the origin of the biomaterial. Bone substitutes used in oral and maxillofacial surgery could be categorized according to their biologic origin and source as autologous bone graft when obtained from the same individual receiving the graft; homologous bone graft, or allograft, when harvested from an individual other than the one receiving the graft; animal-derived heterologous bone graft, or xenograft, when derived from a species other than human; and alloplastic graft, made of bone substitute of synthetic origin. The aim of this review is to describe the most commonly used bone substitutes, according to their origin, and to focus on the biologic events that ultimately lead to the integration of a biomaterial with the host tissue.
Nitric oxide (NO) is a key messenger in physiological and pathological processes in mammals. An excessive NO production is associated with pathological conditions underlying the inflammation response ...as a trigger. Among others, dental pulp inflammation results from the invasion of dentin by pathogenic bacteria. Vital functions of pulp mesenchymal stem cells (DPSCs, dental pulp stem cells), such as mineralization, might be affected by the inducible NOS (iNOS) upregulation. In this context, the iNOS selective inhibition can be considered an innovative therapeutic strategy to counteract inflammation and to promote the regeneration of the dentin-pulp complex. The present work aims at evaluating two acetamidines structurally related to the selective iNOS inhibitor
, namely
and
, in a model of LPS-stimulated primary DPSCs. Our data reveal that
and even more
are promising anti-inflammatory compounds, decreasing IL-6 secretion by enhancing CD73 expression-levels, a protein involved in innate immunity processes and thus confirming an immunomodulatory role of DPSCs. In parallel, cell mineralization potential is retained in the presence of compounds as well as VEGF secretion, and thus their angiogenetic potential. Data presented lay the ground for further investigation on the anti-inflammatory potential of acetamidines selectively targeting iNOS in a clinical context.
CAPE and Neuroprotection: A Review Balaha, Marwa; De Filippis, Barbara; Cataldi, Amelia ...
Biomolecules (Basel, Switzerland),
01/2021, Letnik:
11, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Propolis, a product of the honey bee, has been used in traditional medicine for many years. A hydrophobic bioactive polyphenolic ester, caffeic acid phenethyl ester (CAPE), is one of the most ...extensively investigated active components of propolis. Several studies have indicated that CAPE has a broad spectrum of pharmacological activities as anti-oxidant, anti-inflammatory, anti-viral, anti-fungal, anti-proliferative, and anti-neoplastic properties. This review largely describes CAPE neuroprotective effects in many different conditions and summarizes its molecular mechanisms of action. CAPE was found to have a neuroprotective effect on different neurodegenerative disorders. At the basis of these effects, CAPE has the ability to protect neurons from several underlying causes of various human neurologic diseases, such as oxidative stress, apoptosis dysregulation, and brain inflammation. CAPE can also protect the nervous system from some diseases which negatively affect it, such as diabetes, septic shock, and hepatic encephalopathy, while numerous studies have demonstrated the neuroprotective effects of CAPE against adverse reactions induced by different neurotoxic substances. The potential role of CAPE in protecting the central nervous system (CNS) from secondary injury following various CNS ischemic conditions and CAPE anti-cancer activity in CNS is also reviewed. The structure-activity relationship of CAPE synthetic derivatives is discussed as well.
Eg5 is a protein encoded by KIF11 gene and is primarily involved in correct mitotic cell division. It is also involved in nonmitotic processes such as polypeptide synthesis, protein transport, and ...angiogenesis. The scientific literature sheds light on the ubiquitous functions of KIF11 and its involvement in the onset and progression of different pathologies. This review focuses attention on two main points: (1) the correlation between Eg5 and cancer and (2) the involvement of Eg5 in noncancerous conditions. Regarding the first point, several tumors revealed an overexpression of this kinesin, thus pushing to look for new Eg5 inhibitors for clinical practice. In addition, the evaluation of Eg5 expression represents a crucial step, as its overexpression could predict a poor prognosis for cancer patients. Referring to the second point, in specific pathological conditions, the reduced activity of Eg5 can be one of the causes of pathological onset. This is the case of Alzheimer’s disease (AD), in which A β and Tau work as Eg5 inhibitors, or in acquired immune deficiency syndrome (AIDS), in which Tat‐mediated Eg5 determines the loss of CD 4+ T‐lymphocytes. Reduced Eg5 activity, due to mutations of KIF11 gene, is also responsible for pathological conditions such as microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability (MCLRI) and familial exudative vitreous retinopathy (FEVR). In conclusion, this review highlights the double impact that overexpression or loss of function of Eg5 could have in the onset and progression of different pathological situations. This emphasizes, on one hand, a possible role of Eg5 as a potential biomarker and new target in cancer and, on the other hand, the promotion of Eg5 expression/activity as a new therapeutic strategy in different noncancerous diseases.
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