Microglia-neuron interactions play a crucial role in several neurological disorders characterized by altered neural network excitability, such as epilepsy and neuropathic pain. While a series of ...potential messengers have been postulated as substrates of the communication between microglia and neurons, including cytokines, purines, prostaglandins, and nitric oxide, the specific links between messengers, microglia, neuronal networks, and diseases have remained elusive. Brain-derived neurotrophic factor (BDNF) released by microglia emerges as an exception in this riddle. Here, we review the current knowledge on the role played by microglial BDNF in controlling neuronal excitability by causing disinhibition. The efforts made by different laboratories during the last decade have collectively provided a robust mechanistic paradigm which elucidates the mechanisms involved in the synthesis and release of BDNF from microglia, the downstream TrkB-mediated signals in neurons, and the biophysical mechanism by which disinhibition occurs, via the downregulation of the K+-Cl− cotransporter KCC2, dysrupting Cl−homeostasis, and hence the strength of GABAA- and glycine receptor-mediated inhibition. The resulting altered network activity appears to explain several features of the associated pathologies. Targeting the molecular players involved in this canonical signaling pathway may lead to novel therapeutic approach for ameliorating a wide array of neural dysfunctions.
We discuss on the relative significance of different functional roles potentially served by flavonoids in photoprotection, with special emphasis to their ability to scavenge reactive oxygen species ...(ROS) and control the development of individual organs and whole plant. We propose a model in which chloroplast-located flavonoids scavenge H2O2 and singlet oxygen generated under excess light-stress, thus avoiding programmed cell death. We also draw a picture in which vacuolar flavonoids in conjunction with peroxidases and ascorbic acid constitute a secondary antioxidant system aimed at detoxifying H2O2, which may diffuse out of the chloroplast at considerable rates and enter the vacuole following excess light stress-induced depletion of ascorbate peroxidase. We hypothesize for flavonols key roles as developmental regulators in early and current-day land-plants, based on their ability to modulate auxin movement and auxin catabolism. We show that antioxidant flavonoids display the greatest capacity to regulate key steps of cell growth and differentiation in eukaryotes. These regulatory functions of flavonoids, which are shared by plants and animals, are fully accomplished in the nM concentration range, as likely occurred in early land plants. We therefore conclude that functions of flavonoids as antioxidants and/or developmental regulators flavonoids are of great value in photoprotection. We also suggest that UV-B screening was just one of the multiple functions served by flavonoids when early land-plants faced an abrupt increase in sunlight irradiance.
•Dihydroxy B-ring-substituted flavonoids were already present in early land plants.•Dihydroxy flavonoids effectively scavenge ROS in various sub-cellular compartments.•Antioxidant flavonoids regulate developmental processes in eukaryotic cells.•Antioxidant flavonoids represent a robust trait of terrestrial plants.
: The objective of this study was to compare conventional versus digital impressions for Full-Arch maxillary rehabilitations.
: Patients selected for this study were treated with full-arch ...screw-retained rehabilitations supported by six immediately loaded dental implants. Patients have been scheduled randomly into control (conventional impression group, CIG) and test (digital impression group, DIG) groups respectively for a fully conventional workflow and a fully digital workflow. In both groups, within 24 h, temporary prostheses were delivered. Four months after the implant positioning, the two groups dealt with the fabrication of definitive restorations: conventional pick-up was performed in the control group, and definitive digital impressions were carried out in the test group. The time involved following these two procedures was recorded. Patients underwent intraoral digital radiographs to evaluate the accuracy of the framework-implant connection, check for the presence of voids at the bar-implant connection and measure bone level. Criteria used to assess success at the prosthetic level were the occurrence of prosthetic maintenance, the absence of fractures of the acrylic resin superstructure and voids.
: A total of 50 patients received immediately loaded prostheses supported by six implants (total 300 implants). A fixture and prosthetic survival rate of 100% was observed. All digital X-ray examinations revealed a bar-implant connection accuracy and no voids. Differences that were not statistically significant (
> 0.05) in marginal bone loss were found between control and test groups. Significantly less time was spent to perform digital impression procedure (
< 0.05).
: Clinical and radiological results of the test group advocate a satisfactory accuracy and predictability of the intraoral scanner (IOS) to be a reliable alternative in clinical practice for implant full-arch rehabilitations and suggest fabrication of definitive restorations with a successful marginal fit precision.
•We assess benefits and well-being deriving from visiting urban and peri-urban green areas.•We examine how biodiversity of urban and peri-urban green areas affects well-being.•Biodiversity positively ...affects well-being, especially for urban green areas.•Length of visit to green areas and biodiversity predict well-being through the mediation of perceived restorativeness.•Urban green spaces rich in biodiversity can enhance well-being and promote sustainable lifestyles.
The literature on human experience in green environments had widely showed the positive outcomes of getting in contact with nature. This study addresses the issue of whether urban residents’ evaluations of urban and peri-urban natural settings and the positive outcomes deriving from contact with such settings vary as a function of their biodiversity. A field study assessed benefits and subjective well-being reported by urban residents visiting four different typologies of green spaces, selected on the basis of urban forestry expert criteria according to a 2×2 factorial design. The biodiversity level (low vs. high) was crossed with the setting location (urban vs. peri-urban) as follows: urban squares with green elements, urban parks, pinewood forest plantations, and peri-urban natural protected areas. A questionnaire including measures of length and frequency of visits, perceived restorativeness, and self-reported benefits of the visit to the green spaces was administered in situ to 569 residents of four Italian medium-to-large size cities: Bari, Florence, Rome and Padua. Results showed the positive role of biodiversity upon perceived restorative properties and self-reported benefits for urban and peri-urban green spaces. Consistently with the hypotheses reported herein, a mediation role of perceived restorativeness in the relation between experience of natural settings (i.e. higher level of biodiversity) and self-reported benefits was found. The design and management implications of the findings are discussed.
The hypothesis was tested that isoprenoids and phenylpropanoids play a prominent role in countering photooxidative stress, following the depletion of antioxidant enzyme activity in plants exposed to ...severe drought stress under high solar irradiance and high temperatures.
Platanus × acerifolia, a high isoprene-emitting species, was drought-stressed during summer (WS) and compared with unstressed controls (WW). Water relations and photosynthetic parameters were measured under mild, moderate, and severe drought stress conditions. Volatile and nonvolatile isoprenoids, antioxidant enzymes, and phenylpropanoids were measured with the same time course, but in four different periods of the day.
Drought severely inhibited photosynthesis, whereas it did not markedly affect the photochemical machinery. Isoprene emission and zeaxanthin concentration were higher in WS than in WW leaves, particularly at mild and moderate stresses, and during the hottest hours of the day. The activities of catalase and ascorbate peroxidase steeply declined during the day, while the activity of guaiacol peroxidase and the concentration of quercetin increased during the day, peaking in the hottest hours in both WW and WS plants.
Our experiment reveals a sequence of antioxidants that were used daily by plants to orchestrate defense against oxidative stress induced by drought and associated high light and high temperature. Secondary metabolites seem valuable complements of antioxidant enzymes to counter oxidative stress during the hottest daily hours.
There is a growing body of evidence that flavonoids do not primarily function as UV-B screening pigments in photoprotection. Recent findings support the idea that excess light stress, irrespective of ...the relative proportions of the solar wavebands reaching the leaf surface, up-regulates the biosynthesis of dihydroxy B-ring-substituted flavonoid glycosides, as a consequence of and aimed at countering the generation of ROS. Intriguingly, the very conditions that lead to the inactivation of antioxidant enzymes can also up-regulate the biosynthesis of antioxidant flavonoids, which suggests flavonoids constituting a secondary ROS-scavenging system in plants exposed to severe/prolonged stress conditions. H
2
O
2
may diffuse out of the chloroplast at considerable rates and be transported to the vacuole, the storing site for flavonoids, by tonoplast intrinsic proteins, under severe excess light conditions. We suggest that the unanticipated key role of the vacuole in the ROS homeostasis might be mediated by flavonoids.
(1) Background: The objective of this in vitro study is to evaluate the marginal accuracy of crowns created by CAD/CAM. (2) Methods: A customized chrome-cobalt (Cr-Co) implant abutment simulating a ...maxillary right first molar was fixed in a hemi-maxillary stone model and scanned. In total, 27 crowns were fabricated, including 9 lithium disilicate crowns, 9 composite crowns, and 9 zirconia crowns. The measurements were determined by scanning electron microscopy. Descriptive analysis was performed using the mean and standard deviation, while the Kruskal-Wallis test was performed to determine whether the marginal discrepancies were significantly different between each group (
< 0.05). (3) Results: The lowest marginal gap value was reported for zirconia (21.45 ± 12.58 µm), followed by composite (44.7 ± 24.96 µm) and lithium disilicate (62.28 ± 51.8 µm). The Kruskal-Wallis tests revealed a statistically significant difference (
-value < 0.05) in the mean marginal gaps between different materials. (4) Conclusions: The proposed digital workflow can be a viable alternative for fixed prosthetic rehabilitations. The best performance in terms of marginal gap was achieved by zirconia crowns, but all three materials demonstrate marginal closure below the clinically accepted threshold value (120 µm). Clinical significance: although significant differences were reported, the investigated CAD/CAM materials showed clinically acceptable marginal gaps.
Flavonoids have recently been suggested to have the potential to serve as antioxidants other than effective UV attenuators in photoprotection. Here, we tested the hypothesis that flavonoids ...accumulate in response to “excess light” in the presence or in the absence of UV radiation. In a UV exclusion experiment, we grew
Ligustrum vulgare plants outdoors under 30% or 100% sunlight irradiance, by cutting-off the whole UV waveband. These plants were also exposed to UV irradiance or supplied with 125
mM NaCl at the root zone. Leaves of plants under 100% sunlight irradiance suffered from excess light, which was exacerbated greatly by root zone salinity stress. Salinity stress repressed the activities of antioxidant enzymes, particularly in full sunlight, and led to severe leaf oxidative damage. Dihydroxy B-ring-substituted flavonoids, namely quercetin 3-O- and luteolin 7-O-glycosides, accumulated steeply in response to sunlight irradiance in the absence of UV radiation. UV radiation and root zone NaCl increased, to a similar degree, the concentration of these flavonoids, which have a great potential to scavenge various forms of reactive oxygen. Treatment-induced changes in leaf phenylpropanoid concentration affected antioxidant activities to a greater extent than the UV-screening capacities of leaf extracts. Early responses to an abrupt increase in sunlight irradiance included a steep increase in the concentrations of quercetin derivatives and cyanidin 3-O-glucoside, with the latter negligibly absorbing in the UV-spectral region. In contrast, effective UV attenuators, such as hydroxycinnamates and monohydroxy B-ring flavonoids, were unresponsive to the light treatments. Overall, these findings lead to the hypothesis that flavonoids may have an important antioxidant function in photoprotection. This hypothesis is further corroborated by the large distribution of quercetin and luteolin derivatives in the vacuoles of mesophyll, not only in the corresponding compartments of epidermal cells, but also in full sunlight-treated leaves in the absence of UV radiation. Future experiments aimed at evaluating the relative contribution of flavonoids within the complex antioxidant defense systems operating in the leaf are needed to help conclusively address the relevance of their antioxidant functions in photoprotection.
A major unresolved issue in treating pain is the paradoxical hyperalgesia produced by the gold-standard analgesic morphine and other opiates. We found that hyperalgesia-inducing treatment with ...morphine resulted in downregulation of the K(+)-Cl(-) co-transporter KCC2, impairing Cl(-) homeostasis in rat spinal lamina l neurons. Restoring the anion equilibrium potential reversed the morphine-induced hyperalgesia without affecting tolerance. The hyperalgesia was also reversed by ablating spinal microglia. Morphine hyperalgesia, but not tolerance, required μ opioid receptor-dependent expression of P2X4 receptors (P2X4Rs) in microglia and μ-independent gating of the release of brain-derived neurotrophic factor (BDNF) by P2X4Rs. Blocking BDNF-TrkB signaling preserved Cl(-) homeostasis and reversed the hyperalgesia. Gene-targeted mice in which Bdnf was deleted from microglia did not develop hyperalgesia to morphine. However, neither morphine antinociception nor tolerance was affected in these mice. Our findings dissociate morphine-induced hyperalgesia from tolerance and suggest the microglia-to-neuron P2X4-BDNF-KCC2 pathway as a therapeutic target for preventing hyperalgesia without affecting morphine analgesia.
•Updating von Frey methodology to apply monofilaments more efficiently.•What the test measures: theoretical considerations.•Practical usage of von Frey's hairs in the laboratory ...environment.•Tightening sensory threshold estimates from raw data.•Statistics of (group) threshold estimation.
Here, we reconsider the status quo in testing mechanical sensitivity with von Frey's hairs. The aim is to improve paw withdrawal estimates by integrating current psychometric theory, and to maximise the clinical relevance and statistical power of mechanosensory models. A wealth of research into human tactile stimulus perception may be extended to the quantification of laboratory animal behaviour. We start by reviewing each step of the test, from its design and application through to data analysis. Filament range is assessed as a whole; possible test designs are compared; techniques of filament application to mice and rats are considered; curve fitting software is introduced; possibilities for data pooling and curve fitting are evaluated. A rational update of classical methods in line with recent advances in psychometrics and supported by open source software is expected to improve data homogeneity, and Reduce and Refine animal use in accord with the ‘3R’ principles.
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