William Borges Domingues

The current study aimed to evaluate the in-vitro toxicity and in-vivo antidiabetic effects of a standardized extract from Eugenia uniflora (E. uniflora) fruit, comparing its efficacy to metformin (Met), a widely used anti-hyperglycemic drug. First, toxicity of the extract was determined by MTT assay in 3T3 cell line and primary astrocyte culture. Then Wistar rats were divided into four groups: I- Control, II- type 2 diabetes mellitus (T2DM), III- T2DM + Met and IV- T2DM + E. uniflora. To induce T2DM, groups II, III and IV received a high fat diet (HFD) for 3 weeks followed by a single intraperitoneal (i.p.) dose of streptozotocin (STZ, 35 mg/kg). Animals of group I received normal diet and vehicle (i.p.). Group III received Met (250 mg/kg) and group IV received E. uniflora (200 mg/kg) intragastric pathway, once a day, throughout all experimental protocol. Animals from the groups I and II received water in the same volume. Results showed that cell viability was not affected. In-vivo, E. uniflora and Met prevented the change in serum levels of glucose, cholesterol, LDL, triglyceride and interleukin-6. Furthermore, extract and Met improved oxidative stress markers and antioxidant enzyme activity in the brain (cerebral cortex, hippocampus, striatum). Furthermore, extract enhanced the downstream insulin signaling pathway, including insulin receptor substrate 1, forkhead box protein O-3a, as well as activated the nuclear factor erythroid 2-related factor 2 in the cerebral cortex. This study indicates that E. uniflora extract may have potential in preventing complications associated with T2DM; nevertheless, additional studies are required to confirm these effects and establish their clinical significance. Graphical Abstract

Alzheimer’s Disease (AD) is characterized by memory decline, dysregulation in cholinergic and purinergic signaling, neuroinflammation, and oxidative stress. Current treatments are limited, highlighting the need for new compounds to prevent or delay AD progression. Thiazolidinones have emerged as promising candidates due to their antioxidant, anti-inflammatory, and anticholinesterase properties. The aim of this study was to evaluate the effects of 3-(3-(diethylamino)propyl)-2-(4-(methylthio)phenyl)thiazolidin-4-one (DS27) in a rat model of scopolamine-induced memory deficits. Male rats were divided into groups: I - Control, II - Scopolamine (SCO) (1 mg/kg), III - SCO and DS27 (5 mg/kg), IV - SCO and DS27 (10 mg/kg), V - SCO and donepezil (5 mg/kg). The animals were treated orally with DS27 or donepezil for seven days. On the 8th day, they underwent the open field test and inhibitory avoidance training, followed by intraperitoneal administration SCO. Twenty-four hours later, an inhibitory avoidance test was conducted. Acetylcholinesterase (AChE) activity, oxidative stress, and inflammatory and purinergic parameters were analyzed in the cerebral cortex, hippocampus, cerebrospinal fluid, serum, lymphocytes, and liver. DS27 prevented memory deficits, alterations in AChE activity, and oxidative damage induced by SCO in brain structures. Additionally, DS27 prevented SCO-induced decrease in IL-10 levels, and increase in IL-6, and TNF-α expression in the cerebral cortex, and normalized ATP and ADP hydrolysis in cerebrospinal fluid and lymphocytes. DS27 did not induce oxidative stress in the liver or alter serum biochemical parameters. These findings suggest that DS27 has significant neuroprotective properties and could be a promising alternative for treating neurodegenerative diseases like AD. Graphical Abstract

Among the spectrum of gliomas, glioblastoma stands out as the most aggressive brain tumor affecting the central nervous system. In addressing this urgent medical challenge, exploring therapeutic alternatives becomes imperative to enhance the patient’s prognosis. In this regard, Butia odorata (BO) fruit emerges as a promising candidate due to its array of bioactive compounds, including flavonoids, phenolic acids, and carotenoids, known for their antioxidant, anti-inflammatory, and antitumor properties. Thus, this study aimed to investigate the impact of standardized hydroalcoholic extract of BO on rat C6 and human U87MG glioma cell lines. Cells were exposed to varying extract concentrations (125–2000 μg/mL) for intervals of 0, 2, 4, 6, 24, 48, or 72 h. Then, cell viability, proliferation, colony formation, redox equilibrium parameters, cell migration, and the relative mRNA expression of genes related to gliomagenesis were evaluated. Our findings revealed a reduction in viability, proliferation, colony formation, reactive oxygen species, and nitrite levels in both glioma cell lines upon exposure to the extract. Conversely, an increase in sulfhydryl content and the activity of superoxide dismutase and catalase were observed in both glioma cell lines. No significant changes in viability and proliferation were observed in astrocytes. Furthermore, in the C6 cells only, the BO extract reduced the migration and downregulated the relative mRNA expression of matrix metalloproteinase-2, O6-methylguanine-DNA methyltransferase, nuclear factor-kappa B, interleukin-6 genes, and upregulated caspase-3 gene. These results underscore the promising anti-glioma potential of BO extract, attributed to its diverse bioactive composition.

Natural products offer promising potential for the development of new therapies for Alzheimer's disease (AD). Blackberry fruits are rich in phytochemical compounds capable of modulating pathways involved in neuroprotection. Additionally, drug repurposing and repositioning could also accelerate the development of news treatments for AD. In light of the reduced brain glucose metabolism in AD, an alternative approach has been the use of the drug metformin. Thus, the aim of this study was to evaluate the effect of treatment with blackberry extract in a model of AD induced by streptozotocin (STZ) and compare it with metformin treatment. Male rats were divided into groups: I - Control; II - STZ; III - STZ + blackberry extract (100 mg/kg); IV - STZ + blackberry extract (200 mg/kg) and V - STZ + metformin (150 mg/kg). The animals received intracerebroventricular injection of STZ or buffer. Seven days after the surgical procedure, the animals were treated orally with blackberry extract or metformin for 21 days. Blackberry extract and metformin prevented the memory impairment induced by STZ. In animals of group II, an increase in acetylcholinesterase activity, phosphorylated tau protein, IL-6, oxidative damage, and gene expression of GSK-3β and Nrf2 was observed in the hippocampus. STZ induced a decrease in IL-10 levels and down-regulated the gene expression of Akt1, IRS-1 and FOXO3a. Blackberry extract and metformin prevented the alterations in acetylcholinesterase activity, IL-6, GSK3β, Nrf2, and oxidative damage. In conclusion, blackberry extract exhibits multi-target actions in a model of AD, suggesting new therapeutic potentials for this neurodegenerative disease. Graphical Abstract

In the original article, there was an error. The affirmation present in the title do not correspond to the main conclusion of the study. In the body text the all ideas expressed are correct. During the editing process the change of title was requested for this only this section was changed with an error independent of the main text. Thus, the mistake title was published as follows: “Gene and Blood Analysis Reveal That Transfer from Brackish Water to Freshwater Is Less Stressful to the Silverside Odontesthes humensis”. In contrast to that, our results suggest that brackish water (BW) to freshwater (FW) transfer is more stressful to O. humensis than FW–BW transfer. The alteration of a single word of the title solve the problem.A correction has been made to the title:Gene and Blood Analysis Reveal That Transfer from Brackish Water to Freshwater Is More Stressful to the Silverside Odontesthes humensis.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.

This study investigated the effect of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) to restore the cognitive impairment caused by aging in male Wistar rats. Moreover, modulation of neuroplasticity markers, acetylcholinesterase (AChE) activity, and cholesterol levels was performed. Aged rats were intragastrically treated with 4-PSQ (5 mg/kg) for 7 days. Animals were tested in behavioral tasks, and then plasma (to determine cholesterol levels), hippocampus, and cerebral cortex (to determine neural cell adhesion molecule (NCAM) and polysialyltransferase (PST) levels, and AChE activity) were removed. Our findings demonstrated that treatment of aged rats with 4-PSQ restored short-term and long-term memories in the object recognition tests. 4-PSQ treatment did not restore exploratory activity (rearings) but partially restored locomotor activity (crossings) reduced by aging in the open-field test. Moreover, the compound restored the reduction in the NCAM and PST levels, and AChE activity in cerebral structures, as well as the increase in the plasma cholesterol levels, caused by aging in rats. In conclusion, 4-PSQ restored cognitive impairment caused by aging in rats by modulating synaptic plasticity, cholinergic system, and cholesterol levels.

The silverside (Odontesthes humensis) is a very interesting model for toxicological studies due its high sensitivity and need for good water quality. The aim of this study was to evaluate the effects of Roundup on spermatozoa of O. humensis, after acute exposure. The fish were exposed to 0 and 7.8 mg L⁻¹ (a.e.) of glyphosate, respectively. Through computer-assisted sperm analysis, a significant decrease in concentration, total and progressive motility, average path distance, straight line distance, path average velocity, curved line velocity, straight line velocity linearity, wobble, amplitude of lateral head displacement, cross beat frequency, and motility period of silverside spermatozoa exposed to Roundup was observed. Also, increase in membrane fluidity, ROS production and lipid peroxidation and a decrease in the mitochondrial functionality was observed in spermatozoa of Roundup exposed silversides. It was demonstrated that Roundup exposure in a concentration that can be achieve in natural water bodies soon after its application in fields is able to cause losses in several sperm quality parameters, consequently decreasing the fertilization potential of O. humensis spermatozoa.