Deregulated cellular metabolism is a hallmark of tumors. Cancer cells increase glucose and glutamine flux to provide energy needs and macromolecular synthesis demands. Several studies have been ...focused on the importance of glycolysis and pentose phosphate pathway. However, a neglected but very important branch of glucose metabolism is the hexosamine biosynthesis pathway (HBP). The HBP is a branch of the glucose metabolic pathway that consumes ∼2–5% of the total glucose, generating UDP-GlcNAc as the end product. UDP-GlcNAc is the donor substrate used in multiple glycosylation reactions. Thus, HBP links the altered metabolism with aberrant glycosylation providing a mechanism for cancer cells to sense and respond to microenvironment changes. Here, we investigate the changes of glucose metabolism during epithelial mesenchymal transition (EMT) and the role of O-GlcNAcylation in this process. We show that A549 cells increase glucose uptake during EMT, but instead of increasing the glycolysis and pentose phosphate pathway, the glucose is shunted through the HBP. The activation of HBP induces an aberrant cell surface glycosylation and O-GlcNAcylation. The cell surface glycans display an increase of sialylation α2–6, poly-LacNAc, and fucosylation, all known epitopes found in different tumor models. In addition, modulation of O-GlcNAc levels was demonstrated to be important during the EMT process. Taken together, our results indicate that EMT is an applicable model to study metabolic and glycophenotype changes during carcinogenesis, suggesting that cell glycosylation senses metabolic changes and modulates cell plasticity.
To investigate the associations between the 2 main components of metabolic acidosis (unmeasured anions UA and hyperchloremia) with serum albumin and intact parathormone (iPTH) in patients with ...advanced chronic kidney disease.
Cross-sectional study with advanced chronic kidney disease patients (estimated glomerular filtration rate <30 mL/minute/1.73 m(2)) not receiving phosphate binders, alkali therapy, or vitamin D analogs. Arterial blood sample was collected for biochemical and blood gas analysis. UA and strong ion difference (SID) were calculated according to quantitative acid-base analysis. Reduced SID was used as a measure of hyperchloremia.
Serum albumin and parathormone (iPTH).
A total of 383 patients were included with a mean age of 64.7 ± 16.3 year and a mean estimated glomerular filtration rate of 19.9 ± 12.1 mL/minute/1.73 m(2). Among patients with metabolic acidosis, 45.7% had metabolic acidosis exclusively because of UA and 53.7% had a hyperchloremic component (either mixed metabolic acidosis or pure hyperchloremic metabolic acidosis). Considering the main acid-base status determinants, only UA had a significant correlation with serum albumin (r = -0.278, P < .001). There was no correlation between serum albumin and SID (r = 0.083, P = .156). This is in opposition to serum iPTH, where there was no correlation with UA (r = 0.082, P = .114), but an inverse correlation between iPTH and SID was observed (r = -0.228, P < .001). Multiple linear regressions with all acid-base determinants confirmed these findings.
Our data brings further knowledge on the associations between metabolic acidosis with bone disorders and nutritional status, suggesting that the two main metabolic acidosis components (UA and hyperchloremia) have different effects on serum parathormone and serum albumin.
Most well studied as proteins that restrain the p53 tumor suppressor protein, MDM2 and MDMX have rich lives outside of their relationship to p53. There is much to learn about how these two proteins ...are regulated and how they can function in cells that lack p53. Regulation of MDM2 and MDMX, which takes place at the level of transcription, post-transcription, and protein modification, can be very intricate and is context-dependent. Equally complex are the myriad roles that these two proteins play in cells that lack wild-type p53; while many of these independent outcomes are consistent with oncogenic transformation, in some settings their functions could also be tumor suppressive. Since numerous small molecules that affect MDM2 and MDMX have been developed for therapeutic outcomes, most if not all designed to prevent their restraint of p53, it will be essential to understand how these diverse molecules might affect the p53-independent activities of MDM2 and MDMX.
A lack of control over blood loss can have catastrophic implications, including death. Although several hemostatic medications have been employed to reduce bleeding, a vast majority of them are ...ineffective, expensive, or pose health risks to the patient. To overcome these constraints, chitosan-polyethylene glycol (CS-PEG) hemostatic gels loaded with ethanolic extract of Jatropha mollissima sap (EES) were prepared and their hemostatic, physicochemical, and cytotoxic properties were evaluated. The gels were produced by mixing CS with PEG (an external plasticizer) and EES. The phytochemical analysis revealed a significant concentration of total polyphenols and tannins content in the extract and catechin was identified as one of the key compounds of EES. Infrared spectroscopy analysis revealed the presence of EES in the gels, as well as the chemical interaction between CS and PEG. The gels were thermally stable between 25 and 37 °C (ambient and human body temperature range), had pseudoplastic deformation behavior (rheological properties preserved after shearing), were simple to inject (compression force 30 N), and were biocompatible. In vivo experiments showed that both CS-PEG-EES gels exhibited greater hemostatic action in preventing tail hemorrhage in Wistar rats, with decreased bleeding time and blood weight compared with unloaded CS-PEG gels (control groups) and Hemostank, a commercial product. However, the gel prepared with acetic acid was more efficient in controlling bleeding. These findings reveal that CS-PEG-EES gels can reduce hemorrhages and are a potent, simple, and safe hemostatic agent.
Recent debates on the number of plant species in the vast lowland rain forests of the Amazon have been based largely on model estimates, neglecting published checklists based on verified voucher ...data. Here we collate taxonomically verified checklists to present a list of seed plant species from lowland Amazon rain forests. Our list comprises 14,003 species, of which 6,727 are trees. These figures are similar to estimates derived from nonparametric ecological models, but they contrast strongly with predictions of much higher tree diversity derived from parametric models. Based on the known proportion of tree species in neotropical lowland rain forest communities as measured in complete plot censuses, and on overall estimates of seed plant diversity in Brazil and in the neotropics in general, it is more likely that tree diversity in the Amazon is closer to the lower estimates derived from nonparametric models. Much remains unknown about Amazonian plant diversity, but this taxonomically verified dataset provides a valid starting point for macroecological and evolutionary studies aimed at understanding the origin, evolution, and ecology of the exceptional biodiversity of Amazonian forests.
Exacerbated inflammatory responses are a hallmark of severe coronavirus disease 2019 (COVID-19). Zileuton (Zi) is a selective inhibitor of 5-lipoxygenase, an enzyme involved in the production of ...several inflammatory/pro-resolving lipid mediators. Herein, we investigated the effect of Zi treatment in a severe acute respiratory syndrome (SARS) model. Mouse hepatitis virus (MHV)3-infected mice treated with Zi significantly improved the clinical score, weight loss, cardiopulmonary function, and survival rates compared with infected untreated animals. The protection observed in Zi-treated mice was associated with a lower inflammatory score, reduced dendritic cell-producing tumor necrosis factor (TNF), and increased neutrophil-producing interleukin (IL)-10 in the lungs three days after infection (dpi). At 5 dpi, the lungs of treated mice showed an increase in Th2-, Treg CD4+-, and Treg CD8+-producing IL-10 and reduced Th1 infiltrating cells. Furthermore, similar results were found upon Zi treatment after SARS-CoV-2 infection in transgenic mice expressing the human angiotensin I-converting enzyme 2 (ACE2) receptor driven by the cytokeratin-18 (K18) gene promoter (K18-hACE2), significantly improving the clinical score, weight loss, and lung inflammatory score compared with untreated animals. Our data suggest that Zi protects against developing severe lung disease during SARS induced by betacoronavirus without affecting the host’s capacity to deal with infection.
It has been recently mathematically demonstrated that the percentage increase in serum creatinine (SCr) can delay acute kidney injury (AKI) diagnosis in patients with previous chronic kidney disease ...(CKD). Based on creatinine (Cr) kinetics, it was suggested a new AKI classification using absolute increase in SCr elevation over specified time periods. However, this classification has not been evaluated in clinical studies.
A prospective cohort study evaluated myocardial infarction patients during the first 7 days of hospital stay with daily SCr measurements. They were classified using Kidney Disease Improving Global Outcomes (KDIGO) and Cr kinetics systems. Both classifications were compared by net reclassification improvement (NRI) and area under the receiver operator characteristic (AuROC) curve regarding hospital mortality.
A total of 584 patients were included, of which 34.1% had previous CKD. Patients had more AKI by KDIGO than by Cr kinetics criteria (25.7 versus 18.0%, P < 0.001) and 81 patients (13.9%) had different AKI severity classification. Patients with AKI by KDIGO criteria and non-AKI by Cr kinetics had higher hospital mortality rates than patients with non-AKI using both classifications adjusted mortality odds ratios (ORs): 4.753; 95% confidence interval (CI): 1.119-9.023, P = 0.014. In patients with previous CKD, NRI analysis was 6.2% favoring Cr kinetics criteria. However, there was no difference using the AuROC curve analysis. In patients with no previous CKD, NRI analysis was 33.0%, favoring KDIGO, and this was in accordance with a better AuROC curve (0.828 versus 0.664, P < 0.05).
AKI classification proposed by a Cr kinetics model can be superior when diagnosing patients with previous CKD. However, KDIGO had a better performance in patients with no previous CKD.
Lisdexamfetamine dimesylate (LDX) is a prodrug that requires conversion to d-amphetamine (d-AMPH) for bioactivity. Treatment with d-AMPH induces hyperlocomotion and is regarded as a putative animal ...model of bipolar mania. Therefore, we sought to determine the behavioral and oxidative stress alterations induced by sub-chronic LDX administration as well as their reversal and prevention by lithium in rats. A significant increment in locomotor behavior was induced by LDX (10 and 30mg/kg). To determine Li effects against LDX-induced alterations, in the reversal protocol rats received LDX (10 or 30mg/kg) or saline for 14days. Between days 8 and 14 animals received Li (47.5mg/kg, i.p.) or saline. In the prevention paradigm, rats were pretreated with Li or saline prior to LDX administration. Glutathione (GSH) levels and lipid peroxidation was determined in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) of rats. Lithium prevented LDX-induced hyperlocomotion at the doses of 10 and 30mg/kg, but only reversed LDX-induced hyperlocomotion at dose of 10mg/kg. In addition, both doses of LDX decreased GSH content (in ST and PFC), while Li was able to reverse and prevent these alterations mainly in the PFC. LDX (10 and 30mg/kg) increased lipid peroxidation which was reversed and prevented by Li. In conclusion, LDX-induced hyperlocomotion along with associated increments in oxidative stress show promise as an alternative animal model of mania.
► Bipolar mania is associated with an increase in dopaminergic neurotransmission. ► Lisdexamfetamine dimesylate is a novel stimulant which enhances dopaminergic tone. ► Chronic lisdexamfetamine treatment induced hyperlocomotion in rats. ► Lisdexamfetamine treatment increased oxidative stress in areas of the rat brain. ► Lithium prevented and reversed lisdexamphetamine-induced hyperlocomotion.
Exercise-based interventions can be a safe alternative to improve and maintain physical and mental health during the aging process. The aim of the present study was to evaluate the effects of a ...12-week training program with Dance Exergames on the mood and functional fitness profile of elderly women.
The sample (n = 22) was divided into Exergames (EG, n = 9, 70.6 ± 1.6 years) and Control Groups (CG, n = 13, 73.6 ± 2.2 years). Evaluations were carried out before and after the interventions. Each participant played, in pairs, the electronic game Dance Central 3, with the XBOX 360 Kinect console (Slim, Microsoft, USA). The EG trained for 12 weeks (24 sessions), with two weekly sessions of 50 min and the CG performed manual activities workshops.
In functional fitness, both exercise training with exergame (EG) and the intervention model for the CG did not produce significant effects regarding interaction (group*time). Mood state presented significant effect of time intervention regarding tension (p = <0.001), depression (p = 0.001), anger (p = 0.030), fatigue (p = 0.001), and mental confusion (p = 0.004).
Twelve weeks of training with a dance exergame (for, EG) and manual activities (for, CG) is enough to promote improvements in the mood state of healthy elderly women. This is an interesting result, as it shows that social interaction is as important a component as improving functional capacity.
After successful invasions in the Caribbean and Mediterranean, lionfish (Pterois spp.) have recently invaded another important biogeographical region —the Brazilian Province. In this article, we ...discuss this new invasion, focusing on a roadmap for urgent mitigation of the problem, as well as focused research and management strategies. The invasion in Brazil is already in the consolidation stage, with 352 individuals recorded so far (2020–2023) along 2766 km of coastline. This includes both juveniles and adults, including egg-bearing females, ranging in length from 9.1 to 38.5 cm. Until now, most of the records in the Brazilian coast occurred in the equatorial southwestern Atlantic (99%), mainly on the Amazon mesophotic reefs (15% of the records), northeastern coast of Brazil (45%), and the Fernando de Noronha Archipelago (41%; an UNESCO World Heritage Site with high endemism rate). These records cover a broad depth range (1–110 m depth), twelve protected areas, eight Brazilian states (Amapá, Pará, Maranhão, Piauí, Ceará, Rio Grande do Norte, Paraíba, and Pernambuco) and multiple habitats (i.e., mangrove estuaries, shallow-water and mesophotic reefs, seagrass beds, artificial reefs, and sandbanks), indicating a rapid and successful invasion process in Brazilian waters. In addition, the lack of local knowledge of rare and/or cryptic native species that are potentially vulnerable to lionfish predation raises concerns regarding the potential overlooked ecological impacts. Thus, we call for an urgent integrated approach with multiple stakeholders and solution-based ecological research, real-time inventories, update of environmental and fishery legislation, participatory monitoring supported by citizen science, and a national and unified plan aimed at decreasing the impact of lionfish invasion. The experience acquired by understanding the invasion process in the Caribbean and Mediterranean will help to establish and prioritize goals for Brazil.
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•Records from 2020 to 2023 (at least 352 animals) show that the lionfish invasion is accelerating.•Lionfish was reported in eight Brazilian states, multiple habitats, and 11 marine protected areas.•Records comprise mature and large lionfish individuals (∼38 cm) never previously detected.•The slow and ineffective actions contribute to a fast uncontrolled scenario and escalation of impacts.•A management plan is needed for controlling the spread of lionfish in the Brazilian coast.
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