Conditioned Medium From Reactive Astrocytes Inhibits Proliferation, Resistance, and Migration of p53-Mutant Glioblastoma Spheroid Through GLI-1 Downregulation.

Glioblastoma (GBM) aggressiveness is partly driven by the reactivation of signaling pathways such as Sonic hedgehog (SHH) and the interaction with its microenvironment. SHH pathway activation is one of the phenomena behind the glial transformation in response to tumor growth. The reactivation of the SHH signaling cascade during GBM-astrocyte interaction is highly relevant to understanding the mechanisms used by the tumor to modulate the adjacent stroma. The role of reactive astrocytes considering SHH signaling during GBM progression is investigated using a 3D in vitro model. T98G GBM spheroids displayed significant downregulation of SHH (61.4 ± 9.3%), GLI-1 (6.5 ± 3.7%), Ki-67 (33.7 ± 8.1%), and mutant MTp53 (21.3 ± 10.6%) compared to the CONTROL group when incubated with conditioned medium of reactive astrocytes (CM-AST). The SHH pathway inhibitor, GANT-61, significantly reduced previous markers (SHH = 43.0 ± 12.1%; GLI-1 = 9.5 ± 3.4%; Ki-67 = 31.9 ± 4.6%; MTp53 = 6.5 ± 7.5%) compared to the CONTROL, and a synergistic effect could be observed between GANT-61 and CM-AST. The volume (2.0 ± 0.2 × 107 µm³), cell viability (80.4 ± 3.2%), and migration (41 ± 10%) of GBM spheroids were significantly reduced in the presence of GANT-61 and CM-AST when compared to CM-AST after 72 h (volume = 2.3 ± 0.4 × 107 µm³; viability = 92.2 ± 6.5%; migration = 102.5 ± 14.6%). Results demonstrated that factors released by reactive astrocytes promoted a neuroprotective effect preventing GBM progression using a 3D in vitro model potentiated by SHH pathway inhibition.

Environmental exposure to metal(loid)s and hypertensive disorders of pregnancy: A systematic review.

BACKGROUND: Environmental exposure to metal(loid)s has been associated with adverse effects on human health, but the systemic repercussion of these elements on the development of hypertensive disorders of pregnancy (HDP) is still poorly understood. OBJECTIVE: To summarize evidence published about the influence of environmental exposure to aluminum, arsenic, barium, cadmium, lead, strontium and mercury on the development of HDP. METHODS: We conducted a systematic literature review according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The search strategy was validated by the Peer Review of Electronic Search Strategies. We searched for articles published up to February 2023 in seven databases without language restriction. Two researchers conducted the steps for selection, data extraction and evaluation of the methodological quality of the instruments for epidemiological studies of the Joanna Briggs Institute. Any disagreements were resolved by a third researcher. RESULTS: We obtained 5076 records, of which 37 articles met the inclusion criteria moderate to high methodological quality. Single exposure to metal(loid)s was predominant, and the leading biological matrix analyzed to detect the concentrations from exposure was maternal blood. Lead was the metal investigated the most, and had the largest number of studies showing positive association with HDP. In relation to the other metal(loid)s, higher levels were found in women with HDP in comparison with healthy women, but the finding of a cause-effect relationship was inconsistent. CONCLUSIONS: Although we found evidence of harmful effects of the metal(loid)s studied on human health, the results were inconclusive with regard to HDP. Longitudinal studies that consider prospective investigation, adjustment of confounding factors and the interference of other contaminants in the exacerbation of oxidative stress in women from the preconception phase to the puerperal period should be encouraged.

Metabolic Syndrome and Positive Frailty Screening: A Cross-Sectional Study with Community-Dwelling Older Adults.

Background: Metabolic Syndrome is a set of disorders that characterized by the association of three or more risk factors, like the obesity central, dyslipidemia, borderline blood pressure, hyperglycemia, and the increase of triglycerides. However, these factors also can be associated with pathophysiology of frailty. Objectives: verifying whether the metabolic syndrome is associated to the positive frailty screening in the older people. Design: Cross-sectional study. Participants: 443 older people living in Rio Branco, Brazil. Setting: Data collection was carried out in two stages: a personal interview and blood collection. Measurements: The diagnosis of metabolic syndrome was based on the criteria of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults. The frailty screening was performed using subjective questions validated in a previous study. Descriptive statistics and multinomial logistic regression were used for data analyses. Results: There was a predominance of female older people (69.07%), aged between 60 and 79 years (87.13%), with an income greater than or equal to one minimum wage (72.09%), no cognitive decline (75.94%) and depressive symptoms (63.31%), independent for BADL (86.46%) and dependent for IADL (51.69%). From the total sample, 56.88% of the older people were identified as frail, 34.09% pre-frail and 9.03% non frail. The prevalence of metabolic syndrome was 51.69%. After adjusting by the independent variables, an association between metabolic syndrome and pre-frailty was observed, and older people with metabolic syndrome were more likely to be prefrail (RRR=2.36; 95%CI=1.08-5.18). Conclusion: The metabolic syndrome was associated to the increase chance of screening for prefrailty in the older people evaluated, which reinforces the needy to establish preventive measures in relation to the metabolic syndrome to avoid frailty in the older people.

Effect of hospitalisation on the rate of surgical site infection in dogs with Penrose drains.

OBJECTIVES: The aim of this study is to retrospectively report complication and infection rates associated with the use of Penrose drains in a large population of dogs; and to compare complication and infection rates of dogs hospitalised for maintenance of their Penrose drains with those that were discharged home with their drains in place. MATERIALS AND METHODS: We performed a retrospective search of medical records from 2014 to 2022 for dogs that had a Penrose drain placed into a wound in one institution. Our population was sub-divided into dogs discharged home with a drain in place; dogs discharged only after drain removal; and dogs recovered part of the time in hospital and part at home (with the drain in situ). Postoperative complications were graded using the Clavien-Dindo scale. RESULTS: Two hundred and eight dogs were included. The overall complication rate was 40.9% (85/208), with most complications considered minor. The overall infection rate was 16.9% (35/207). Dogs discharged home with the drain in situ <24 hours after surgery (n=136) had similar complication (39.0%) and infection (16.2%) rates to dogs kept hospitalised for drain care (n=50, 42.9%, 18.4%) and dogs kept hospitalised for >24 hours but discharged with the drain in situ (n=18, 50.0%, 22.2%). CLINICAL SIGNIFICANCE: Our study results show no significant influence on the complication or infection rates between dogs that were hospitalised for drain care and those discharged home with drains in situ within 24 hours of surgery.

Effects of long-term exposure to MST-312 on lung cancer cells tumorigenesis: Role of SHH/GLI-1 axis.

Replicative immortality is a key feature of cancer cells and it is maintained by the expression of telomerase, a promising target of novel therapies. Long-term telomerase inhibition can induce resistance, but the mechanisms underlying this process remain unclear. The Sonic hedgehog pathway (SHH) is an embryogenic pathway involved in tumorigenesis and modulates the transcription of telomerase. We evaluated the effects of long-term treatment of the telomerase inhibitor MST-312 in morphology, proliferation, resistance, and in the SHH pathway molecules expression levels in lung cancer cells. Cells treated for 12 weeks with MST-312 showed changes in morphology, such as spindle-shaped cells, and a shift in the distribution of F-ACTIN from cortical to diffuse. Treatment also significantly reduced cells' efficiency to form spheroids and their clonogenic potential, independently of the cell cycle and telomeric DNA content. Moreover, GLI-1 expression levels were significantly reduced after 12 weeks of MST-312 treatment, indicating a possible inhibition of this signaling axis in the SHH pathway, without hindering NANOG and OCT4 expression. Here, we described a novel implication of long-term treatment with MST-312 functionally and molecularly, shedding new light on the molecular mechanisms of this drug in vitro.

GANT-61 Induces Autophagy and Apoptosis in Glioblastoma Cells despite their heterogeneity.

Glioblastoma (GBM) is the most common adult primary tumor of the CNS characterized by rapid growth and diffuse invasiveness into the brain parenchyma. The GBM resistance to chemotherapeutic drugs may be due to the presence of cancer stem cells (CSCs). The CSCs activate the same molecular pathways as healthy stem cells such as WNT, Sonic hedgehog (SHH), and Notch. Mutations or deregulations of those pathways play a key role in the proliferation and differentiation of their surrounding environment, leading to tumorigenesis. Here we investigated the effect of SHH signaling pathway inhibition in human GBM cells by using GANT-61, considering stem cell phenotype, cell proliferation, and cell death. Our results demonstrated that GANT-61 induces apoptosis and autophagy in GBM cells, by increasing the expression of LC3 II and cleaved caspase 3 and 9. Moreover, we observed that SHH signaling plays a crucial role in CSC phenotype maintenance, being also involved in the epithelial-mesenchymal transition (EMT) phenotype. We also noted that SHH pathway modulation can regulate cell proliferation as revealed through the analysis of Ki-67 and c-MYC expressions. We concluded that SHH signaling pathway inhibition may be a promising therapeutic approach to treat patients suffering from GBM refractory to traditional treatments.

Cyclopamine sensitizes glioblastoma cells to temozolomide treatment through Sonic hedgehog pathway.

AIM: Glioblastoma is an extremely aggressive glioma, resistant to radio and chemotherapy usually performed with temozolomide. One of the main reasons for glioblastoma resistance to conventional therapies is due to the presence of cancer stem-like cells. These cells could recapitulate some signaling pathways important for embryonic development, such as Sonic hedgehog. Here, we investigated if the inhibitor of the Sonic hedgehog pathway, cyclopamine, could potentiate the temozolomide effect in cancer stem-like cells and glioblastoma cell lines in vitro. MAIN METHODS: The viability of glioblastoma cells exposed to cyclopamine and temozolomide treatment was evaluated by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay while the induction of apoptosis was assessed by western blot. The stemness properties of glioma cells were verified by clonogenic and differentiation assay and the expression of stem cell markers were measured by fluorescence microscopy and western blot. KEY FINDINGS: The glioblastoma viability was reduced by cyclopamine treatment. Cyclopamine potentiated temozolomide treatment in glioblastoma cell lines by inducing apoptosis through activation of caspase-3 cleaved. Conversely, the combined treatment of cyclopamine and temozolomide potentiated the stemness properties of glioblastoma cells by inducing the expression of SOX-2 and OCT-4. SIGNIFICANCE: Cyclopamine plays an effect on glioblastoma cell lines but also sensibilize them to temozolomide treatment. Thus, first-line treatment with Sonic hedgehog inhibitor followed by temozolomide could be used as a new therapeutic strategy for glioblastoma patients.

Neuromechanisms of SARS-CoV-2: A Review.

Recent studies have suggested the neuroinvasive potential of severe acute respiratory coronavirus 2 (SARS-CoV-2). Notably, neuroinvasiveness might be involved in the pathophysiology of coronavirus disease 2019 (COVID-19). Some studies have demonstrated that synapse-connected routes may enable coronaviruses to access the central nervous system (CNS). However, evidence related to the presence of SARS-CoV-2 in the CNS, its direct impact on the CNS, and the contribution to symptoms suffered, remain sparse. Here, we review the current literature that indicates that SARS-CoV-2 can invade the nervous system. We also describe the neural circuits that are potentially affected by the virus and their possible role in the progress of COVID-19. In addition, we propose several strategies to understand, diagnose, and treat the neurological symptoms of COVID-19.

Secondary glioblastoma metastasis outside the central nervous system in a young HIV-infected patient.

Glioblastoma is the most common adult primary brain tumor that occurs in the central nervous system and is characterized by rapid growth and diffuse invasiveness with respect to the adjacent brain parenchyma, which renders surgical resection inefficient. Although it is a highly infiltrative tumor, it is rarely disseminated beyond the central nervous system, wherein extracranial metastasis is a unique but rare manifestation of this kind of tumor. It is very common for acquired immunodeficiency syndrome (AIDS) patients to be infected with the human immunodeficiency virus (HIV), which suggests that a possible association between HIV infection and tumor development exists. In this paper, we present a new case of a young patient's HIV-associated glioblastoma, with glioblastoma metastasis within the T9 vertebral body and lymph nodes in the anterior neck tissue. Initially, the patient was diagnosed with a grade III plastic astrocytoma. The patient lived a normal life for a year while being treated with temozolomide, radiotherapy, and highly active antiretroviral therapy. However, the tumor quickly evolved into a glioblastoma. We believe that the drastic progression of the tumor from a grade III anaplastic astrocytoma to a metastatic glioblastoma is due to the HIV infection that the patient had acquired, which contributed to a weakened immune system, thus accelerating progression of the cancer.

Use of an Extract of Annona muricata Linn to Prevent High-Fat Diet Induced Metabolic Disorders in C57BL/6 Mice.

Annona muricata Linn, commonly known as graviola, is one of the most popular plants used in Brazil for weight loss. The aim of this study is to evaluate the therapeutic effects of three different doses (50 mg/kg, 100 mg/kg, and 150 mg/kg) of aqueous graviola leaf extract (AGE) supplemented by oral gavage, on obese C57BL/6 mice. Food intake, body weight, an oral glucose tolerance test (OGTT), an insulin sensitivity test, quantification of adipose tissue cytokines, weight of fat pads, and serum biochemical and histological analyses of the liver, pancreas, and epididymal adipose tissue were measured. AGE had an anti-inflammatory effect by increasing IL-10 at doses of 50 and 100 mg/kg. Regarding the cholesterol profile, there was a significant decrease in LDL-cholesterol levels in the AGE 150 group, and VLDL-cholesterol and triglycerides in the AGE 100 and 150 groups. There was an increase in HDL cholesterol in the AGE 150 group. The extract was able to reduce the adipocyte area of the epididymal adipose tissue in the AGE 100 and 150 groups. According to the histological analysis of the liver and pancreas, no significant difference was found among the groups. There were no significant effects of AGE on OGTT and serum fasting glucose concentration. However, the extract was effective in improving glucose tolerance in the AGE 150 group.

Glioblastoma Therapy in the Age of Molecular Medicine.

Glioblastoma (GBM) is the most common and fatal primary malignant brain tumor. Despite advances in the understanding of the biology of gliomas, little has changed in the treatment of these tumors in the past decade. Phase III clinical trials showed no benefit for the use of bevacizumab in newly diagnosed patients, leading to a renewed search for new antiangiogenic drugs, as well as immunotherapeutic approaches, including checkpoint inhibitors, chimeric antigen receptor T cells, and intracerebral CpG-oligodeoxynucleotides. The emerging role of infiltrating microglia and macrophages, and of metabolic alterations, is also being taken into account in preclinical research and drug development. In this review, we discuss progress in the search for new therapeutic strategies, particularly approaches focusing on the tumor microenvironment.

A highlight on Sonic hedgehog pathway.

Hedgehog (Hh) signaling pathway plays an essential role during vertebrate embryonic development and tumorigenesis. It is already known that Sonic hedgehog (Shh) pathway is important for the evolution of radio and chemo-resistance of several types of tumors. Most of the brain tumors are resistant to chemotherapeutic drugs, consequently, they have a poor prognosis. So, a better knowledge of the Shh pathway opens an opportunity for targeted therapies against brain tumors considering a multi-factorial molecular overview. Therefore, emerging studies are being conducted in order to find new inhibitors for Shh signaling pathway, which could be safely used in clinical trials. Shh can signal through a canonical and non-canonical way, and it also has important points of interaction with other pathways during brain tumorigenesis. So, a better knowledge of Shh signaling pathway opens an avenue of possibilities for the treatment of not only for brain tumors but also for other types of cancers. In this review, we will also highlight some clinical trials that use the Shh pathway as a target for treating brain cancer.

Interaction strength between different grazers and macroalgae mediated by ocean acidification over warming gradients.

Since the past century, rising CO2 levels have led to global changes (ocean warming and acidification) with subsequent effects on marine ecosystems and organisms. Macroalgae-herbivore interactions have a main role in the regulation of marine community structure (top-down control). Gradients of warming prompt complex non-linear effects on organism metabolism, cascading into altered trophic interactions and community dynamics. However, not much is known on how will acidification and grazer assemblage composition shape these effects. Within this context, we aimed to assess the combined effects of warming gradients and acidification on macroalgae-herbivore interactions, using three cosmopolitan species, abundant in the Iberian Peninsula and closely associated in nature: the amphipod Melita palmata, the gastropod Gibbula umbilicalis, and the green macroalga Ulva rigida. Under two CO2 treatments (ΔCO2 ≃ 450 µatm) across a temperature gradient (13.5, 16.6, 19.9 and 22.1 °C), two mesocosm experiments were performed to assess grazer consumption rates and macroalgae-herbivore interaction, respectively. Warming (Experiment I and II) and acidification (Experiment II) prompted negative effects in grazer's survival and species-specific differences in consumption rates. M. palmata was shown to be the stronger grazer per biomass (but not per capita), and also the most affected by climate stressors. Macroalgae-herbivore interaction strength was markedly shaped by the temperature gradient, while simultaneous acidification lowered thermal optimal threshold. In the near future, warming and acidification are likely to strengthen top-down control, but further increases in disturbances may lead to bottom-up regulated communities. Finally, our results suggest that grazer assemblage composition may modulate future macroalgae-herbivore interactions.

The risks of introduction of the Amazonian palm Euterpe oleracea in the Atlantic rainforest.

The introduction of a species may alter ecological processes of native populations, such as pollination and dispersal patterns, leading to changes in population structure. When the introduced and the native species are congeners, interference in pollination can also lead to hybridization. We aimed to understand the ecological aspects of Euterpe oleracea introduction in the Atlantic forest and the possible consequences for the conservation of the native congener Euterpe edulis. We analysed the population structure of palm populations, including hybrids, and observed the interaction with frugivorous birds of both palm species after E. oleracea introduction. We observed that E. edulis had significantly lower density and a smaller number of seedlings when occurring with E. oleracea. Native and introduced Euterpe species shared nine frugivorous bird species. E. oleracea and hybrids had dispersed outside the original planting area. Consequently, the risks of introduction of E. oleracea may mostly be related to the disruption of interactions between E. edulis and frugivorous birds and the spontaneous production of hybrids. Finally, the cultivation of E. oleracea and hybrids in Atlantic rainforest could affect the conservation of the already endangered E. edulis.

The risks of introduction of the Amazonian palm Euterpe oleracea in the Atlantic rainforest / Os riscos da introdução da palmeira amazônica Euterpe oleracea na Floresta Atlântica

Abstract The introduction of a species may alter ecological processes of native populations, such as pollination and dispersal patterns, leading to changes in population structure. When the introduced and the native species are congeners, interference in pollination can also lead to hybridization. We aimed to understand the ecological aspects of Euterpe oleracea introduction in the Atlantic forest and the possible consequences for the conservation of the native congener Euterpe edulis. We analysed the population structure of palm populations, including hybrids, and observed the interaction with frugivorous birds of both palm species after E. oleracea introduction. We observed that E. edulis had significantly lower density and a smaller number of seedlings when occurring with E. oleracea. Native and introduced Euterpe species shared nine frugivorous bird species. E. oleracea and hybrids had dispersed outside the original planting area. Consequently, the risks of introduction of E. oleracea may mostly be related to the disruption of interactions between E. edulis and frugivorous birds and the spontaneous production of hybrids. Finally, the cultivation of E. oleracea and hybrids in Atlantic rainforest could affect the conservation of the already endangered E. edulis.

Resumo A introdução de uma espécie pode alterar processos ecológicos de populações nativas, tais como padrões de polinização e dispersão, levando a mudanças na estrutura populacional. Quando espécies introduzidas e nativas são congêneres, a interferência na polinização pode levar também à hibridização. Nossos objetivos foram entender os aspectos ecológicos da introdução de Euterpe oleracea na Floresta Atlântica e as possíveis consequências sobre a conservação da congênere nativa Euterpe edulis. Para isso, analisamos a estrutura populacional, incluindo híbridos, e observamos a interação de aves frugívoras com ambas as espécies de palmeira após a introdução de E. oleracea. Observamos que E. edulis apresentou densidade total e número de plântulas menores quando coocorrente com E. oleracea. As palmeiras congenéricas compartilharam nove espécies de aves frugívoras. E. oleracea e híbridos foram dispersos além da área original de plantio. Consequentemente, os riscos da introdução de E. oleracea podem estar principalmente relacionados com o possível deslocamento de interações entre E. edulis e aves frugívoras e com a produção de híbridos. Desta forma, o cultivo de E. oleracea e híbridos podem afetar a conservação da já ameaçada E. edulis.

Impacts of climate and land use changes on the hydrological and erosion processes of two contrasting Mediterranean catchments.

The impacts of climate and land use changes on streamflow and sediment export were evaluated for a humid (São Lourenço) and a dry (Guadalupe) Mediterranean catchment, using the SWAT model. SWAT was able to produce viable streamflow and sediment export simulations for both catchments, which provided a baseline for investigating climate and land use changes under the A1B and B1 emission scenarios for 2071-2100. Compared to the baseline scenario (1971-2000), climate change scenarios showed a decrease in annual rainfall for both catchments (humid: -12%; dry: -8%), together with strong increases in rainfall during winter. Land use changes were derived from a socio-economic storyline in which traditional agriculture is replaced by more profitable land uses (i.e. corn and commercial forestry at the humid site; sunflower at the dry site). Climate change projections showed a decrease in streamflow for both catchments, whereas sediment export decreased only for the São Lourenço catchment. Land use changes resulted in an increase in streamflow, but the erosive response differed between catchments. The combination of climate and land use change scenarios led to a reduction in streamflow for both catchments, suggesting a domain of the climatic response. As for sediments, contrasting results were observed for the humid (A1B: -29%; B1: -22%) and dry catchment (A1B: +222%; B1: +5%), which is mainly due to differences in the present-day and forecasted vegetation types. The results highlight the importance of climate-induced land-use change impacts, which could be similar to or more severe than the direct impacts of climate change alone.

Activated Microglia-Induced Deficits in Excitatory Synapses Through IL-1ß: Implications for Cognitive Impairment in Sepsis.

Recent clinical studies have shown that sepsis survivors may develop long-term cognitive impairments. The cellular and molecular mechanisms involved in these events are not well understood. This study investigated synaptic deficits in sepsis and the involvement of glial cells in this process. Septic animals showed memory impairment and reduced numbers of hippocampal and cortical excitatory synapses, identified by synaptophysin/PSD-95 co-localization, 9 days after disease onset. The behavioral deficits and synaptophysin/PSD-95 co-localization were rescued to normal levels within 30 days post-sepsis. Septic mice presented activation of microglia and reactive astrogliosis, which are hallmarks of brain injury and could be involved in the associated synaptic deficits. We treated neuronal cultures with conditioned medium derived from cultured astrocytes (ACM) and microglia (MCM) that were either non-stimulated or stimulated with lipopolysaccharide (LPS) to investigate the molecular mechanisms underlying synaptic deficits in sepsis. ACM and MCM increased the number of synapses between cortical neurons in vitro, and these effects were antagonized by LPS stimulation. LPS-MCM reduced the number of synapses by 50%, but LPS-ACM increased the number of synapses by 500%. Analysis of the composition of these conditioned media revealed increased levels of IL-1ß in LPS-MCM. Furthermore, inhibition of IL-1ß signaling through the addition of a soluble IL-1ß receptor antagonist (IL-1 Ra) fully prevented the synaptic deficit induced by LPS-MCM. These results suggest that sepsis induces a transient synaptic deficit associated with memory impairments mediated by IL-1ß secreted by activated microglia.

LPA-primed astrocytes induce axonal outgrowth of cortical progenitors by activating PKA signaling pathways and modulating extracellular matrix proteins.

Lysophosphatidic acid (LPA) is one of the main membrane-derived lysophospholipids, inducing diverse cellular responses like cell proliferation, cell death inhibition, and cytoskeletal rearrangement, and thus is important in many biological processes. In the central nervous system (CNS), post-mitotic neurons release LPA extracellularly whereas astrocytes do not. Astrocytes play a key role in brain development and pathology, producing various cytokines, chemokines, growth factors, and extracellular matrix (ECM) components that act as molecular coordinators of neuron-glia communication. However, many molecular mechanisms underlying these events remain unclear-in particular, how the multifaceted interplay between the signaling pathways regulated by lysophospholipids is integrated in the complex nature of the CNS. Previously we showed that LPA-primed astrocytes induce neuronal commitment by activating LPA1-LPA2 receptors. Further, we revealed that these events were mediated by modulation and organization of laminin levels by astrocytes, through the induction of the epidermal growth factor receptor (EGFR) signaling pathway and the activation of the mitogen-activated protein (MAP) kinase (MAPK) cascade in response to LPA (Spohr et al., 2008, 2011). In the present work, we aimed to answer whether LPA affects astrocytic production and rearrangement of fibronectin, and to investigate the mechanisms involved in neuronal differentiation and maturation of cortical neurons induced by LPA-primed astrocytes. We show that PKA activation is required for LPA-primed astrocytes to induce neurite outgrowth and neuronal maturation and to rearrange and enhance the production of fibronectin and laminin. We propose a potential mechanism by which neurons and astrocytes communicate, as well as how such interactions drive cellular events such as neurite outgrowth, cell fate commitment, and maturation.

Gliomas and the vascular fragility of the blood brain barrier.

Astrocytes, members of the glial family, interact through the exchange of soluble factors or by directly contacting neurons and other brain cells, such as microglia and endothelial cells. Astrocytic projections interact with vessels and act as additional elements of the Blood Brain Barrier (BBB). By mechanisms not fully understood, astrocytes can undergo oncogenic transformation and give rise to gliomas. The tumors take advantage of the BBB to ensure survival and continuous growth. A glioma can develop into a very aggressive tumor, the glioblastoma (GBM), characterized by a highly heterogeneous cell population (including tumor stem cells), extensive proliferation and migration. Nevertheless, gliomas can also give rise to slow growing tumors and in both cases, the afflux of blood, via BBB is crucial. Glioma cells migrate to different regions of the brain guided by the extension of blood vessels, colonizing the healthy adjacent tissue. In the clinical context, GBM can lead to tumor-derived seizures, which represent a challenge to patients and clinicians, since drugs used for its treatment must be able to cross the BBB. Uncontrolled and fast growth also leads to the disruption of the chimeric and fragile vessels in the tumor mass resulting in peritumoral edema. Although hormonal therapy is currently used to control the edema, it is not always efficient. In this review we comment the points cited above, considering the importance of the BBB and the concerns that arise when this barrier is affected.

Natural regeneration of the herbaceous community in a semiarid region in Northeastern Brazil.

This study aimed to describe and compare the interannual changes in the diversity and population structure of herbaceous plants in an anthropogenic area that has been regenerating for 15 years and to identify the similarities and differences in the biological attributes of the community compared with the characteristics of a regenerating conserved area. In total, 105 plots measuring 1 m(2) were established. In each plot, the herbaceous plants were identified, and their height and stem diameter were measured for two consecutive years. The herbaceous flora of the anthropogenic area was represented by 86 species in 70 genera and 27 families, and there were no significant differences in the average richness between years. The conserved area was represented by 71 species in 63 genera and 35 families, and there was a significant difference in the total richness between areas and between years, except when comparing the richness between the conserved area and the anthropogenic area during the second year. Considering both the anthropogenic and conserved areas, 123 herbaceous species were listed, and the similarity between areas was 60 %. For the anthropogenic area, the floristic similarity between years was 95 %, and in the fragment of the conserved area, the similarity was 74 %. The diversity and density were significantly different between years and between areas. Given these results, this study suggests that 15 years of natural regeneration for the caatinga is not sufficient to reestablish its native flora with respect to its herbaceous component.