Phytotoxic impact of bifunctionalized silver nanoparticles (AgNPs-Cit-L-Cys) and silver nitrate (AgNO3) on chronically exposed callus cultures of Populus nigra L.

Owing to the unique physicochemical properties and the low manufacturing costs, silver nanoparticles (AgNPs) have gained growing interest and their application has expanded considerably in industrial and agricultural sectors. The large-scale production of these nanoparticles inevitably entails their direct or indirect release into the environment, raising some concerns about their hazardous aspects. Callus culture represents an important tool in toxicological studies to evaluate the impact of nanomaterials on plants and their potential environmental risk. In this study, we investigated the chronic phytotoxic effects of different concentrations of novel bifunctionalized silver nanoparticles (AgNPs-Cit-L-Cys) and silver nitrate (AgNO3) on callus culture of Populus nigra L., a pioneer tree species in the riparian ecosystem. Our results showed that AgNPs-Cit-L-Cys were more toxic on poplar calli compared to AgNO3, especially at low concentration (2.5 mg/L), leading to a significant reduction in biomass production, accompanied by a decrease in protein content, a significant increase in both lipid peroxidation level, ascorbate peroxidase (APX), and catalase (CAT) enzymatic activities. In addition, these findings suggested that the harmful activity of AgNPs-Cit-L-Cys might be correlated with their physicochemical properties and not solely attributed to the released Ag+ ions and confirmed that AgNPs-Cit-L-Cys phytoxicity is associated to oxidative stress.

Multicellular Liver Organoids: Generation and Importance of Diverse Specialized Cellular Components.

Over 40,000 patients in the United States are estimated to suffer from end-stage liver disease and acute hepatic failure, for which liver transplantation is the only available therapy. Human primary hepatocytes (HPH) have not been employed as a therapeutic tool due to the difficulty in growing and expanding them in vitro, their sensitivity to cold temperatures, and tendency to dedifferentiate following two-dimensional culture. The differentiation of human-induced pluripotent stem cells (hiPSCs) into liver organoids (LO) has emerged as a potential alternative to orthotropic liver transplantation (OLT). However, several factors limit the efficiency of liver differentiation from hiPSCs, including a low proportion of differentiated cells capable of reaching a mature phenotype, the poor reproducibility of existing differentiation protocols, and insufficient long-term viability in vitro and in vivo. This review will analyze various methodologies being developed to improve hepatic differentiation from hiPSCs into liver organoids, paying particular attention to the use of endothelial cells as supportive cells for their further maturation. Here, we demonstrate why differentiated liver organoids can be used as a research tool for drug testing and disease modeling, or employed as a bridge for liver transplantation following liver failure.

Indocyanine Green Angiography for Quality Assessment of Renal Graft Before Transplantation: A Pilot Study.

OBJECTIVES: Criteria for donation have been expanded to meet the great demand for organ transplant, resulting in different tools and classifications to help physicians to better assess the quality of the transplanted kidney. In this study, we evaluated the use of indocyanine green angiography as an additional tool to evaluate the renal microcirculation and the quality of the potential kidney graft. MATERIALS AND METHODS: All kidneys from extended criteria donors or donors after cardiac death available for transplant underwent indocyanine green angiog-raphy before implantation and after reconditioning, when hypothermic perfusion was required. We performed fluorescent angiography with a 10-mm-view laparoscope connected to a high-definition camera system while a solution of indocyanine green and Celsior was injected into the renal artery. We compared fluorescence intensities with postoperative graft function and then analyzed increases in fluorescence intensity before and after hypothermic machine perfusion treatment. RESULTS: In transplanted kidneys preserved in traditional cold storage, we found a statistically significant difference in fluorescence intensity values between groups with early graft function and delayed graft function. Fluorescence intensity increased significantly in all perfused kidneys after hypothermic machine perfusion treatment, indicating that intensity was directly proportional to improved renal microcirculation. Among 21 kidneys retrieved for transplant that adhered to the inclusion criteria, 11 were examined histopathologically, with a Karpinski score ranging from 2 to 7. The kidney that scored 7 was immediately discarded. Five underwent hypothermic pulsatile perfusion since they came from donors after cardiac death. Fluorescence intensity increased significantly in all perfused kidneys (4/5 were closest to doubling). Histopathological evaluations and Karpinski scores of the grafts indicated that all 5 were considered suitable for transplant. CONCLUSIONS: Indocyanine green angiography can be used in the future as an additional useful tool to help physicians to assess graft quality before implantation.

Liver Trauma: Until When We Have to Delay Surgery? A Review.

Liver involvement after abdominal blunt trauma must be expected, and in up to 30% of cases, spleen, kidney, and pancreas injuries may coexist. Whenever hemodynamics conditions do not contraindicate the overcoming of the ancient dogma according to which exploratory laparotomy should be performed after every major abdominal trauma, a CT scan has to clarify the liver lesions so as to determine the optimal management strategy. Except for complete vascular avulsion, no liver trauma grade precludes nonoperative management. Every attempt to treat the injured liver by avoiding a strong surgical approach may be considered. Each time, a nonoperative management (NOM) consisting of a basic "wait and see" attitude combined with systemic support and blood replacement are inadequate. Embolization should be considered to stop the bleeding. Percutaneous drainage of collections, endoscopic retrograde cholangiopancreatography (ERCP) with papilla sphincterotomy or stent placement and percutaneous transhepatic biliary drainage (PTBD) may avoid, or at least delay, surgical reconstruction or resection until systemic and hepatic inflammatory remodeling are resolved. The pathophysiological principle sustaining these leanings is based on the opportunity to limit the further release of cell debris fragments acting as damage-associated molecular patterns (DAMPs) and the following stress response associated with the consequent immune suppression after trauma. The main goal will be a faster recovery combined with limited cell death of the liver through the ischemic events that may directly follow the trauma, exacerbated by hemostatic procedures and surgery, in order to reduce the gross distortion of a regenerated liver.

Immune-Mediated Mechanisms in Patients Testing Positive for SARS-CoV-2: Protocol for a Multianalysis Study.

BACKGROUND: The novel coronavirus has a high mortality rate (over 1% for patients older than 50 years). This can only be partially ascribed to other comorbidities. A possible explanation is a factor that assures a prompt response to SARS-CoV-2 in younger people, independent from the novelty of the virus itself. A factor is believed to stimulate the immune system and provide immunity against more antigens. The only external stimulation received by healthy people is vaccination (eg, the diphtheria, tetanus, and pertussis [DTP] vaccine). One hypothesis is that vaccination helps develop specific immunity but generates sprouting immunity against antigens in transit. The underlying immunological phenomena are the "bystander effect" and "trained immunity." The developed immunity gives protection for years until it naturally fades out. After the fifth decade of life, the immune system is almost incompetent when a viral infection occurs, and thus, at this stage, the novel coronavirus can enter the body and cause acute respiratory distress syndrome. OBJECTIVE: The initial aim is to demonstrate that blood monocytes and natural killer cells show overpowering hyperactivity, while CD4+ and CD8+ T cells experience impediments to their defensive functions in patients with severe SARS-CoV-2 infection. The secondary objectives are to correlate clinical data and vaccination history with laboratory immune patterns in order to identify protective factors. Subsequently, we are also interested in characterizing the phenotypes and state of the degree of activation of peripheral blood mononuclear cells, including monocytes, natural killer cells, and CD4+ and CD8+ T cells, in healthy subjects vaccinated with the Pfizer vaccine. METHODS: Data will be collected using the following 3 approaches: (1) an experimental analysis to study the innate immune response and to identify genetic profiles; (2) an epidemiological analysis to identify the patients' vaccination history; and (3) a clinical analysis to detect the immunological profile. RESULTS: The protocol was approved by the Ethics Committee on April 16, 2020, and the study started on April 27, 2020. As of February 2021, enrollment has been completed. Immunological analysis is ongoing, and we expect to complete this analysis by December 2022. CONCLUSIONS: We will recognize different populations of patients, each one with a specific immunological pattern in terms of cytokines, soluble factor serum levels, and immune cell activity. Anamnestic data, such as preceding vaccinations and comorbidities, biochemical findings like lymphocyte immunophenotyping, and pre-existing persistent cytomegalovirus infection, allow depicting the risk profile of severe COVID-19. Proof of the roles of these immunological phenomena in the development of COVID-19 can be the basis for the implementation of therapeutic immunomodulatory treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT04375176; https://clinicaltrials.gov/ct2/show/NCT04375176. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29892.

A systems-level analysis highlights microglial activation as a modifying factor in common epilepsies.

AIMS: The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems-level analysis. METHODS: Imaging-based cortical structural maps from a large-scale epilepsy neuroimaging study were overlaid with highly spatially resolved human brain gene expression data from the Allen Human Brain Atlas. Cell-type deconvolution, differential expression analysis and cell-type enrichment analyses were used to identify differences in cell-type distribution. These differences were followed up in post-mortem brain tissue from humans with epilepsy using Iba1 immunolabelling. Furthermore, to investigate a causal effect in cortical thinning, cell-type-specific depletion was used in a murine model of acquired epilepsy. RESULTS: We identified elevated fractions of microglia and endothelial cells in regions of reduced cortical thickness. Differentially expressed genes showed enrichment for microglial markers and, in particular, activated microglial states. Analysis of post-mortem brain tissue from humans with epilepsy confirmed excess activated microglia. In the murine model, transient depletion of activated microglia during the early phase of the disease development prevented cortical thinning and neuronal cell loss in the temporal cortex. Although the development of chronic seizures was unaffected, the epileptic mice with early depletion of activated microglia did not develop deficits in a non-spatial memory test seen in epileptic mice not depleted of microglia. CONCLUSIONS: These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.

Predictive Models for the Functional Recovery of Transplanted Kidney.

BACKGROUND: Renal transplantation is the gold standard treatment for end-stage renal disease, however, in 20% of cases, the graft develops a delayed graft function (DGF) that is associated with both early and late worsening of the outcome. The aim of this study was to examine and validate in a population of transplanted patients the appropriateness of the predictive score systems of DGF available to identify patients who might take advantage of a tailored immunosuppressive therapy. MATERIALS AND METHODS: We conducted a systematic review of the literature to identify articles concerning scoring systems predicting DGF to identify those applicable to the study population and subsequently comparing their appropriateness for defining the most accurate one. RESULTS: From an analysis of the scientific literature, we found 7 scoring systems predicting DGF. Of these, 3 can be calculated for the study population. We enrolled 247 renal transplants in the study. DGF was recorded in 41 cases (15.95%). The Irish score recognized 25 of 41 cases (60.98%), the Jeldres score 41 of 41 cases (100%), and the Chapal score only 7 of 41 (17.07%). Although the Irish score did not identify all cases of DGF, the analysis of data revealed that it is the most accurate, with area under the receiver operating characteristic almost overlapping. CONCLUSIONS: The study resulted in some interesting and promising conclusions about the predictability of DGF, defining the Irish score as the most reliable. This result can be considered the fundamental requirement to develop a custom therapeutic algorithm to be applied to all recipients with higher probability of developing DGF.

Laparoscopy in Emergency: Why Not? Advantages of Laparoscopy in Major Emergency: A Review.

A laparoscopic approach is suggested with the highest grade of recommendation for acute cholecystitis, perforated gastroduodenal ulcers, acute appendicitis, gynaecological disorders, and non-specific abdominal pain (NSAP). To date, the main qualities of laparoscopy for these acute surgical scenarios are clearly stated: quicker surgery, faster recovery and shorter hospital stay. For the remaining surgical emergencies, as well as for abdominal trauma, the role of laparoscopy is still a matter of debate. Patients might benefit from a laparoscopic approach only if performed by experienced teams and surgeons which guarantee a high standard of care. More precisely, laparoscopy can limit damage to the tissue and could be effective for the reduction of the overall amount of cell debris, which is a result of the intensity with which the immune system reacts to the injury and the following symptomatology. In fact, these fragments act as damage-associated molecular patterns (DAMPs). DAMPs, as well as pathogen associated molecular patterns (PAMPs), are recognised by both surface and intracellular receptors of the immune cells and activate the cascade which, in critically ill surgical patients, is responsible for a deranged response. This may result in the development of progressive and multiple organ dysfunctions, manifesting with acute respiratory distress syndrome (ARDS), coagulopathy, liver dysfunction and renal failure. In conclusion, none of the emergency surgical scenarios preclude laparoscopy, provided that the surgical tactic could ensure sufficient cleaning of the abdomen in addition to resolving the initial tissue damage caused by the "trauma".

Indocyanine Green Angiography for Quality Assessment of the Kidney During Transplantation: An Outcome Predictor Prospective Study.

BACKGROUND: Microvascular damage is the main cause of delayed graft function (DGF) after kidney transplant. Assessing its extent may be helpful in predicting DGF to achieve better postoperative management, especially in terms of an immunosuppressive regimen. Our aim was to explore the capability of intraoperative indocyanine green (ICG) angiography to examine the microvasculature of the kidney. METHODS: We conducted a prospective cohort study on 37 kidney transplant recipients in a high-volume kidney transplant center. During surgery, after graft implant, an ICG angiography was performed through a high-definition Storz camera system (Karl Storz GmbH, Tuttlingen, Germany) with successive quantitative assessment of fluorescence using Icy bioimage analysis. RESULTS: All transplanted kidneys that showed immediate recovery of their function had a fluorescent intensity ≥49.953 with a mean of 96.930 ± 21. The fluorescence intensity for kidneys that showed a delayed recovery of their function never exceeded 55.648, and the mean was 37.718 ± 13. The difference between the 2 groups was statistically significant with a P value < .001. The only kidney that never recovered showed a fluorescence intensity consistently <25.220, the lowest detected. CONCLUSIONS: This study demonstrates that intraoperative ICG angiography may be used to assess the microvasculature of the graft. A statistically significant difference in terms of fluorescent intensity can be highlighted between kidneys that immediately recover their function and those with delayed recovery. Further larger studies are needed to confirm the capability of the technique to predict DGF to optimize the transplanted patients' management.

In-depth characterization of a mouse model of post-traumatic epilepsy for biomarker and drug discovery.

Post-traumatic epilepsy (PTE) accounts for 5% of all epilepsies and 10-20% of the acquired forms. The latency between traumatic brain injury (TBI) and epilepsy onset in high-risk patients offers a therapeutic window for intervention to prevent or improve the disease course. However, progress towards effective treatments has been hampered by the lack of sensitive prognostic biomarkers of PTE, and of therapeutic targets. There is therefore a pressing clinical need for preclinical PTE models suitable for biomarker discovery and drug testing. We characterized in-depth a model of severe TBI induced by controlled cortical impact evolving into PTE in CD1 adult male mice. To identify sensitive measures predictive of PTE development and severity, TBI mice were longitudinally monitored by video-electrocorticography (ECoG), examined by MRI, and tested for sensorimotor and cognitive deficits and locomotor activity. At the end of the video-ECoG recording mice were killed for brain histological analysis. PTE occurred in 58% of mice with frequent motor seizures (one seizure every other day), as determined up to 5 months post-TBI. The weight loss of PTE mice in 1 week after TBI correlated with the number of spontaneous seizures at 5 months. Moreover, the recovery rate of the sensorimotor deficit detected by the SNAP test before the predicted time of epilepsy onset was significantly lower in PTE mice than in those without epilepsy. Neuroscore, beam walk and cognitive deficit were similar in all TBI mice. The increase in the contusion volume, the volume of forebrain regions contralateral to the lesioned hemisphere and white matter changes over time assessed by MRI were similar in PTE and no-PTE mice. However, brain histology showed a more pronounced neuronal cell loss in the cortex and hippocampus contralateral to the injured hemisphere in PTE than in no-PTE mice. The extensive functional and neuropathological characterization of this TBI model, provides a tool to identify sensitive measures of epilepsy development and severity clinically useful for increasing PTE prediction in high-risk TBI patients. The high PTE incidence and spontaneous seizures frequency in mice provide an ideal model for biomarker discovery and for testing new drugs.

miR147b: A novel key regulator of interleukin 1 beta-mediated inflammation in human astrocytes.

Astrocytes are important mediators of inflammatory processes in the brain and seem to play an important role in several neurological disorders, including epilepsy. Recent studies show that astrocytes produce several microRNAs, which may function as crucial regulators of inflammatory pathways and could be used as therapeutic target. We aim to study which miRNAs are produced by astrocytes during IL-1ß mediated inflammatory conditions in vitro, as well as their functional role and to validate these findings in human epileptogenic brain tissue. Sequencing was used to assess miRNA and mRNA expression in IL-1ß-stimulated human fetal astrocyte cultures. miRNAs were overexpressed in cell cultures using miRNA mimics. Expression of miRNAs in resected brain tissue from patients with tuberous sclerosis complex or temporal lobe epilepsy with hippocampal sclerosis was examined using in situ hybridization. Two differentially expressed miRNAs were found: miR146a and miR147b, which were associated with increased expression of genes related to the immune/inflammatory response. As previously reported for miR146a, overexpression of miR147b reduced the expression of the pro-inflammatory mediators IL-6 and COX-2 after IL-1ß stimulation in both astrocyte and tuberous sclerosis complex cell cultures. miR146a and miR147b overexpression decreased proliferation of astrocytes and promoted neuronal differentiation of human neural stem cells. Similarly to previous evidence for miR146a, miR147b was increased expressed in astrocytes in epileptogenic brain. Due to their anti-inflammatory effects, ability to restore aberrant astrocytic proliferation and promote neuronal differentiation, miR146a and miR147b deserve further investigation as potential therapeutic targets in neurological disorders associated with inflammation, such as epilepsy.

Inhibition of IL-1ß Signaling Normalizes NMDA-Dependent Neurotransmission and Reduces Seizure Susceptibility in a Mouse Model of Creutzfeldt-Jakob Disease.

Creutzfeldt-Jakob disease (CJD) is a neurodegenerative disorder caused by prion protein (PrP) misfolding, clinically recognized by cognitive and motor deficits, electroencephalographic abnormalities, and seizures. Its neurophysiological bases are not known. To assess the potential involvement of NMDA receptor (NMDAR) dysfunction, we analyzed NMDA-dependent synaptic plasticity in hippocampal slices from Tg(CJD) mice, which model a genetic form of CJD. Because PrP depletion may result in functional upregulation of NMDARs, we also analyzed PrP knock-out (KO) mice. Long-term potentiation (LTP) at the Schaffer collateral-commissural synapses in the CA1 area of ∼100-d-old Tg(CJD) mice was comparable to that of wild-type (WT) controls, but there was an inversion of metaplasticity, with increased GluN2B phosphorylation, which is indicative of enhanced NMDAR activation. Similar but less marked changes were seen in PrP KO mice. At ∼300 d of age, the magnitude of LTP increased in Tg(CJD) mice but decreased in PrP KO mice, indicating divergent changes in hippocampal synaptic responsiveness. Tg(CJD) but not PrP KO mice were intrinsically more susceptible than WT controls to focal hippocampal seizures induced by kainic acid. IL-1ß-positive astrocytes increased in the Tg(CJD) hippocampus, and blocking IL-1 receptor signaling restored normal synaptic responses and reduced seizure susceptibility. These results indicate that alterations in NMDA-dependent glutamatergic transmission in Tg(CJD) mice do not depend solely on PrP functional loss. Moreover, astrocytic IL-1ß plays a role in the enhanced synaptic responsiveness and seizure susceptibility, suggesting that targeting IL-1ß signaling may offer a novel symptomatic treatment for CJD.SIGNIFICANCE STATEMENT Dementia and myoclonic jerks develop in individuals with Creutzfeldt-Jakob disease (CJD), an incurable brain disorder caused by alterations in prion protein structure. These individuals are prone to seizures and have high brain levels of the inflammatory cytokine IL-1ß. Here we show that blocking IL-1ß receptors with anakinra, the human recombinant form of the endogenous IL-1 receptor antagonist used to treat rheumatoid arthritis, normalizes hippocampal neurotransmission and reduces seizure susceptibility in a CJD mouse model. These results link neuroinflammation to defective neurotransmission and the enhanced susceptibility to seizures in CJD and raise the possibility that targeting IL-1ß with clinically available drugs may be beneficial for symptomatic treatment of the disease.

Investigation on metal tolerance and phytoremoval activity in the poplar hybrid clone "Monviso" under Cu-spiked water: Potential use for wastewater treatment.

A serious concern for the environmental and human health is represented by the increasing copper (Cu) occurrence in agricultural soils and waters, because of the possible food contamination and bioaugmentation along the trophic chain. The request for the decontamination of different matrices with an environmentally sustainable technology as the phytoremediation should be addressed by selecting plant materials with improved pollutant tolerance and removal capability. With this purpose, plants of the hybrid poplar clone "Monviso" (Populus×generosa A. Henry×P. nigra L.) were grown in growth chamber under hydroponics and exposed to excess Cu concentrations (T1, 75µM Cu; T2, 150µM Cu), selected as about 5 and 10 times higher than those allowed by the Italian regulation on water use. Results evidenced a notable Cu tolerance by poplar plants, particularly at the lowest Cu concentration. At organ level, the root system was the most affected by Cu treatment, especially in T2-exposed plants. Copper determinations revealed that the metal was mostly bioaccumulated in the roots, with a limited amount reaching the shoots. Chlorophyll content and fluorescence analyses confirmed the visible symptoms in leaves, highlighting a good physiological status in T1-exposed plants. Contrarily, an impairment of the main processes associated to photosynthesis was observed in T2-exposed plants also by gas exchange measurements. Remarkably, the Cu content analysis of the spiked water solutions revealed that poplar plants succeeded in removing almost the 50% of the total Cu amount added. These results strengthen the evidence that poplar plants represent a useful eco-friendly bio-tool for the decontamination of metal polluted waters.

Effects of a ladle furnace slag added to soil on morpho-physiological and biochemical parameters of Amaranthus paniculatus L. plants.

Industrial slag from steelwork activities is considered a by-product by the EU legislation and it can be used for civil construction. In this work, an experiment in a greenhouse was conducted over a 6-week period to investigate the effect of soil enrichment with ladle furnace slag on morpho-physiological parameters of Amaranthus paniculatus L. plants. Results showed that the addition of 5% (w/w) slag to soil did not alter the plant growth, highlighting a high tolerance to this slag concentration. Contrarily, plants cultivated in a soil with 10% (w/w) slag showed a marked reduction both in growth and biometric parameters. Moreover, plants grown on a slag-rich soil (20% w/w) highlighted a very low survival rate. This behaviour was confirmed by the biochemical and physiological investigations on chlorophyll a and b content, gas exchange and chlorophyll fluorescence analyses. Metal(loid)s determination showed the accumulation of Ni, Se, Sn, As, Sb and Cd in 10% slag-treated plants, while revealed an increase in Ni, Cd, As and Pb in 5% slag-treated plants. Results are discussed highlighting the profitability of the cultivation of Amaranthus plants on slag enriched soil, as this plant species is largely used both as feedstock for energy production and for environmental restoration.

Blockade of the IL-1R1/TLR4 pathway mediates disease-modification therapeutic effects in a model of acquired epilepsy.

We recently discovered that forebrain activation of the IL-1 receptor/Toll-like receptor (IL-1R1/TLR4) innate immunity signal plays a pivotal role in neuronal hyperexcitability underlying seizures in rodents. Since this pathway is activated in neurons and glia in human epileptogenic foci, it represents a potential target for developing drugs interfering with the mechanisms of epileptogenesis that lead to spontaneous seizures. The lack of such drugs represents a major unmet clinical need. We tested therefore novel therapies inhibiting the IL-1R1/TLR4 signaling in an established murine model of acquired epilepsy. We used an epigenetic approach by injecting a synthetic mimic of micro(mi)RNA-146a that impairs IL1R1/TLR4 signal transduction, or we blocked receptor activation with antiinflammatory drugs. Both interventions when transiently applied to mice after epilepsy onset, prevented disease progression and dramatically reduced chronic seizure recurrence, while the anticonvulsant drug carbamazepine was ineffective. We conclude that IL-1R1/TLR4 is a novel potential therapeutic target for attaining disease-modifications in patients with diagnosed epilepsy.

Modulation of neuronal excitability by immune mediators in epilepsy.

A complex set of inflammatory molecules and their receptors has been described in epileptogenic foci in different forms of pharmacoresistant epilepsies. By activating receptor-mediated pathways in neurons, these molecules have profound neuromodulatory effects that are distinct from their canonical activation of immune functions. Importantly, the neuromodulatory actions of some inflammatory molecules contribute to hyperexcitability in neural networks that underlie seizures. This review summarizes recent findings related to the role of cytokines (IL-1beta and TNF-alpha) and danger signals (HMGB1) in decreasing seizure threshold, thereby contributing to seizure generation and the associated neuropathology. We will discuss preclinical studies suggesting that pharmacological inhibition of specific inflammatory signals may be useful to treat drug-resistant seizures in human epilepsy, and possibly arrest epileptogenesis in individuals at risk of developing the disease.

Assessment of physiological and biochemical responses, metal tolerance and accumulation in two eucalypt hybrid clones for phytoremediation of cadmium-contaminated waters.

Eucalyptus is a promising species for ecological restoration but plant performances under environmental constraints need to be better investigated. In particular, the toxic effects of metals on this plant species are poorly described in the literature. In this work, morpho-physiological and biochemical responses to cadmium were analysed in two eucalypt genotypes (hybrid clones of Eucalyptus camaldulensis × Eucalyptus globulus ssp. bicostata J.B. Kirkp named Velino ex 7 and Viglio ex 358) exposed for 3 weeks to 50 µM CdSO4 under hydroponics. The two eucalypt clones showed a different sensitivity to the metal. The growth reduction caused by cadmium was less than 30% in clone Velino and about 50% in clone Viglio. Cadmium mostly accumulated in plant roots and, to a lesser extent, in stem, as highlighted by the low translocation factor (Tf) measured in both clones. Net photosynthesis measurement, chlorophyll fluorescence images, transpiration values and chlorophyll content revealed a cadmium-induced impairment of physiological processes at the leaf level, which was more evident in clone Viglio. Metal binding and antioxidative compound content was differentially affected by cadmium exposure in the two eucalypt clones. Particularly, the content of thiols like cysteine and glutathione, organic acids like oxalate and citrate, and polyamines were markedly modulated in plant organs by metal treatment and highlighted different defence responses between the clones. Cadmium tolerance and accumulation ability of the eucalypt clones were evaluated and the potential of E. camaldulensis for the reclamation of metal polluted-waters is discussed.

Evaluation of nickel tolerance in Amaranthus paniculatus L. plants by measuring photosynthesis, oxidative status, antioxidative response and metal-binding molecule content.

Among metals, Ni has been indicated as one of the most dangerous for the environment, and plants exposed to this metal are frequently reported to undergo a severe stress condition. In this work, the tolerance responses to different Ni concentrations at physiological and biochemical levels were evaluated in Amaranthus paniculatus L., a plant species previously characterised for their ability to phytoremove Ni from metal-spiked water. Results indicated a good metal tolerance of this plant species at environmentally relevant Ni concentrations, while clear symptoms of oxidative damages were detected at higher Ni concentrations, both in roots and leaves, by measuring lipid peroxide content. At the photosynthetic level, pigment content determination, chlorophyll fluorescence image analysis and gas-exchange parameter measurements revealed a progressive impairment of the photosynthetic machinery at increasing Ni concentrations in the solution. Regarding biochemical mechanisms involved in antioxidative defence and metal binding, antioxidative enzyme (ascorbate peroxidase, APX; catalase, CAT; guaiacol peroxidase, GPX; superoxide dismutase, SOD) activity, polyamine (PA) content, polyamine oxidase (PAO) activity and organic acid (OA) content were differently affected by Ni concentration in the growth solution. A role for GPX, SOD, PAs, and oxalic and citric acid in Ni detoxification is suggested. These results can contribute to elucidate the tolerance mechanisms carried out by plants when facing environmentally relevant Ni concentrations and to identify some traits characterising the physiological and biochemical responses of Amaranthus plants to the presence and bioaccumulation of Ni.