A significant fraction of patients are affected by persistent fear and anxiety. Currently, there are several anxiolytic drug options, however their clinical outcomes do not fully manage the symptoms. ...Here, we evaluated the effects of a bromazepam‑palladium derivative 2-{(7-bromo-2-oxo-1,3-dihydro-2H-1,4-benzodiazepin-5-il)pyridinyl-κ2-N,N}chloropalladium(II), (BMZ)PdCl2, on fear/anxiety and memory-related behavior in mice. For this, female Swiss mice were treated intraperitoneally (i.p.) with saline (NaCl 0.9%) or (BMZ)PdCl2 (0.5, 5.0, or 50 μg/kg). After 30 min, different tests were performed to evaluate anxiety, locomotion, and memory. We also evaluated the acute toxicity of (BMZ)PdCl2 using a cell viability assay (neutral red uptake assay), and whether the drugs mechanism of action involves the γ-aminobutyric acid type A (GABAA) receptor complex by pre-treating animals with flumazenil (1.0 mg/kg, i.p., a competitive antagonist of GABAA-binding site). Our results demonstrate that (BMZ)PdCl2 induces an anxiolytic-like phenotype in the elevated plus-maze test and that this effect can be blocked by flumazenil. Furthermore, there were no behavioral alterations induced by (BMZ)PdCl2, as evaluated in the light-dark box, open field, and step-down passive avoidance tests. In the acute toxicity assay, (BMZ)PdCl2 presented IC50 and LD50 values of 218 ± 60 μg/mL and 780 ± 80 mg/kg, respectively, and GSH category 4. Taken together, our results show that the anxiolytic-like effect of acute treatment with (BMZ)PdCl2 occurs through the modulation of the benzodiazepine site in the GABAA receptor complex. Moreover, we show indications that (BMZ)PdCl2 does not promote sedation and amnesia and presents the same toxicity as the bromazepam prototype.
We evaluated the effects of a bromazepam-palladium complex on fear, anxiety and memory-related behaviors in mice. The results showed that the anxiolytic-like occurs through modulation of the benzodiazepine site in the GABAA receptor complex. There are indications that the complex does not promote sedation, amnesia and toxicity higher than bromazepam. Display omitted
•Palladium-bromazepam complex, (BMZ)PdCl2.•(BMZ)PdCl2 showed an anxiolytic-like effect.•(BMZ)PdCl2 did not affect locomotor activity and memory.•(BMZ)PdCl2 showed similar acute toxicity to bromazepam.
The discovery of disease-specific biomarkers, such as microRNAs (miRNAs), holds the potential to transform the landscape of Amyotrophic Lateral Sclerosis (ALS) by facilitating timely diagnosis, ...monitoring treatment response, and accelerating drug discovery. Such advancement could ultimately improve the quality of life and survival rates for ALS patients. Despite more than a decade of research, no miRNA biomarker candidate has been translated into clinical practice. We conducted a systematic review and meta-analysis to quantitatively synthesize data from original studies that analyzed miRNA expression from liquid biopsies via PCR and compared them to healthy controls. Our analysis encompasses 807 miRNA observations from 31 studies, stratified according to their source tissue. We identified consistently dysregulated miRNAs in serum (hsa-miR-3665, -4530, -4745–5p, −206); blood (hsa-miR-338–3p, -183–5p); cerebrospinal fluid (hsa-miR-34a-3p); plasma (hsa-miR-206); and neural-enriched extracellular vesicles from plasma (hsa-miR-146a-5p, −151a-5p, −10b-5p, −29b-3p, and −4454). The meta-analyses provided further support for the upregulation of hsa-miR-206, hsa-miR-338–3p, hsa-miR-146a-5p and hsa-miR-151a-5p, and downregulation of hsa-miR-183–5p, hsa-miR-10b-5p, hsa-miR-29b-3p, and hsa-miR-4454 as consistent indicators of ALS across independent studies. Our findings provide valuable insights into the current understanding of miRNAs' dysregulated expression in ALS patients and on the researchers’ choices of methodology. This work contributes to the ongoing efforts towards discovering disease-specific biomarkers.
Ethnomedicinal studies in the Amazon community and in the Northeast region of Brazil highlight the use of Libidibia ferrea fruits for the treatment of gastric problems. However, there are no data in ...the literature of this pharmacological activity. Thus, the aim of this paper is to provide a scientific basis for the use of the dry extract of L. ferrea pods (DELfp) for the treatment of peptic ulcers. Phytochemical characterization was performed by HPLC/MS. In vitro antioxidant activity was assessed using DPPH, ABTS, phosphomolybdenum, and superoxide radical scavenging activity. The gastroprotective activity, the ability to stimulate mucus production, the antisecretory activity, and the influence of -SH and NO compounds on the antiulcerogenic activity of DELfp were evaluated. The healing activity was determined by the acetic acid-induced chronic ulcer model. Anti-Helicobacter pylori activity was investigated. HPLC/MS results identified the presence of phenolic compounds, gallic acid and ellagic acid, in DELfp. The extract showed antioxidant activity in vitro. In ulcers induced by absolute ethanol and acidified ethanol, the ED50 values of DELfp were 113 and 185.7 mg/kg, respectively. DELfp (100, 200, and 400 mg/kg) inhibited indomethacin-induced lesions by 66.7, 69.6, and 65.8%, respectively. DELfp (200 mg/kg) reduced gastric secretion and H+ concentration in the gastric contents and showed to be independent of nitric oxide (NO) and dependent on sulfhydryl (-SH) compounds in the protection of the gastric mucosa. In the chronic ulcer model, DELfp reduced the area of the gastric lesion. DELfp also showed anti-H. pylori activity. In conclusion, DELfp showed antioxidant, gastroprotective, healing, and antiulcerogenic activities. The mechanism of these actions seems to be mediated by different pathways and involves the reduction of gastric secretion and H+ concentration, dependence on sulfhydryl compounds, and anti-H. pylori activity. All these actions support the medicinal use of this species in the management of peptic ulcers.
The prediction of biological processes, which involve growth and plant development, is possible via the adjustment of mathematical models. In forest areas, these models assist in management ...practices, silviculture, harvesting, and soil fertility. Diameter, basal area, and height are predictors of volume and biomass estimates in forest stands. This study utilized different non-linear models for estimating biomass and nutrient values in the aerial biomass and roots of an unmanaged eucalypt stand in Cerrado dystrophic soil. It was hypothesized that the models would estimate the nutrients of the aboveground biomass and roots after meeting the selection and validation criteria. By statistical analysis of the parameters and subsequent validation, the Schumacher–Hall model was presented to be the best fit for biomass and nutrients. This result confirmed the ability of different variables, including diameter, basal area, and height, to be predicted. Estimating the nutrient values in the aboveground biomass and roots allowed a better understanding of the quality of the vegetal residues that remained in the soil. For dystrophic soils, which occur in the Cerrado, these estimates become even more relevant.
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•This is the first report of Perkinsus olseni in C. gasar and in Brazil.•Molecular analyses showed that both P. marinus and P. olseni infected C. gasar.•Perkinsus sp. infection ...prevalences were higher among the cultured oysters.•Perkinsus sp. prevalences varied, being maximum in summer and minimum in winter.
Brazilian production of bivalve molluscs is small but expanding, especially in the northeastern region where the native oysters Crassostrea rhizophorae and C. gasar are abundant, and tropical weather promotes their rapid growth. Studies on bivalve pathology are scarce in Brazil, with only a few employing techniques for detecting protozoan pathogens listed by the World Organisation for Animal Health (OIE). In 2008, a Perkinsus sp. was reported for the first time in Brazil, infecting C. rhizophorae oysters from a wild population in Ceará state, NE Brazil. Recently P. marinus was detected in the same oyster species in nearby Paraíba state. These findings highlighted the need to expand knowledge on the presence and impacts of Perkinsus spp. on Brazilian oyster populations. The current investigation evaluated Perkinsus sp. infections among wild and cultured C. gasar mangrove oysters from the estuary of the Rio São Francisco, Sergipe state, NE Brazil. Our results show that Perkinsus sp. infections occurred commonly in oysters of both groups, at prevalences that were frequently higher among cultured oysters. Prevalences varied seasonally, with maximum values during summer (January) of 57% and 80% for wild and cultured oysters respectively, and minimum values during winter (July). Results of DNA sequencing, in situ hybridization assays, and phylogenetic analyses showed dual- and single-pathogen infections by P. marinus and/or P. olseni in the tested oysters.
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