Search

Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is one of the most important neglected diseases in Latin America. The limited use of the current nitro-derivative-based chemotherapy highlights the need for alternative drugs and the identification of their molecular targets. In this study, we investigated the trypanocidal effect of the sesquiterpene lactone dehydroleucodine (DhL) and its derivatives, focusing on the antioxidative defense of the parasites. DhL and two derivatives, at lesser extent, displayed antiproliferative effect on the parasites. This effect was blocked by the reducing agent glutathione (GSH). Treated parasites exhibited increased intracellular ROS concentration and trypanothione synthetase activity, accompanied by mitochondrial swelling. Although molecular dynamics studies predicted that GSH would not interact with DhL, 1H-NMR analysis confirmed that GSH could protect parasites by interacting with the lactone. When parasites overexpressing mitochondrial tryparedoxin peroxidase were incubated with DhL, its effect was attenuated. Overexpression of cytosolic tryparedoxin peroxidase also provided some protection against DhL. These findings suggest that DhL induces oxidative imbalance in T. cruzi, offering new insights into potential drug targets against this parasite. [ABSTRACT FROM AUTHOR]

Water contamination with dyes such as rhodamine B (RhB) affects living organisms and ecosystems. Heterogeneous photocatalysis has been successfully employed in RhB degradation. In this work, different Bi2WO6 (BWO)-carbonaceous material nanocomposites (NCs) were synthesized using simple and environmentally friendly procedures and applied as photocatalysts for the visible degradation of RhB. The decoration of BWO with nitrogen-doped graphene (NG) and NG functionalized with citric acid (FNG) enhanced the photocatalytic activity of NCs. The synthesis and performance of NG-BWO and FNG-BWO catalysts have no precedent. RhB and other dyes (methylene blue, crystal violet, and methyl orange) were used to test the activity of BWO NCs under low-power white LEDs irradiation. The 1.25FNG-BWO (1.25% FNG content) photocatalyst achieved the highest activity toward RhB degradation among the other prepared NCs, attaining 100% in 150 min with 19 W white LEDs, which is comparable to the activity reported in other studies using similar NCs and high-power (300–500 W) xenon and tungsten lamps, also representing a considerable energy saving of the process. The photoelectrochemical assays figured out that diffusion phenomena are responsible for RhB degradation rate using BWO NCs, and that the photocurrent changes are related mainly to their Eg. Photocatalytic cycles corroborated the high stability of 1.25FNG-BWO. Besides, holes (h+) and superoxides ( O 2 ∙ - ) are the main oxidizing species of RhB, and the mechanism of charge transfer and RhB photodegradation using 1.25FNG-BWO was postulated. [ABSTRACT FROM AUTHOR]

Many military veterans who experienced blast-related traumatic brain injuries in the conflicts in Iraq and Afghanistan currently suffer from chronic cognitive and mental health problems that include depression and post-traumatic stress disorder (PTSD). Male rats exposed to repetitive low-level blast develop cognitive and PTSD-related behavioral traits that are present for more than 1 year after exposure. We previously reported that a group II metabotropic receptor (mGluR2/3) antagonist reversed blast-induced behavioral traits. In this report, we explored mGluR2/3 expression following blast exposure in male rats. Western blotting revealed that mGluR2 protein (but not mGluR3) was increased in all brain regions studied (anterior cortex, hippocampus, and amygdala) at 43 or 52 weeks after blast exposure but not at 2 weeks or 6 weeks. mGluR2 RNA was elevated at 52 weeks while mGluR3 was not. Immunohistochemical staining revealed no changes in the principally presynaptic localization of mGluR2 by blast exposure. Administering the mGluR2/3 antagonist LY341495 after behavioral traits had emerged rapidly reversed blast-induced effects on novel object recognition and cued fear responses 10 months following blast exposure. These studies support alterations in mGluR2 receptors as a key pathophysiological event following blast exposure and provide further support for group II metabotropic receptors as therapeutic targets in the neurobehavioral effects that follow blast injury. [ABSTRACT FROM AUTHOR]

The fabrication of cathodes with carbonized Agave tequilana bagasse for Li–S batteries is performed for the first time. Three porous carbonaceous structures are developed and studied to elucidate the best carbon textural properties in terms of their surface area and pore size distribution: hierarchical porosity, highly microporous, and nonporous material, for sulfur hosting in Li–S cathodes. N2 physorption, scanning electron microscopy, infrared spectroscopy, and potentiometric titrations analysis are performed to determine the textural, morphology, and physicochemical properties. The fabricated coin cells, CR2032, with cathodes made of mesoporous carbons, display a high discharge current (≈1600 mAh g−1), superior performance, and cyclability up to 250 cycles. The performance of batteries is found to be strongly influenced by surface area and pore size of the carbon materials. The carbonized tequila bagasse hosting sulfur can be very useful to fabricate cathodes for Li–S batteries with high initial capacity and cycling stability. [ABSTRACT FROM AUTHOR]

In this study, hybrid polyacrylic acid and Schizochytrium sp. microalgae (PAA/Schizo) microgels were synthesized by inverse emulsion assisted by ultrasound using the cell wall fraction as crosslinker. Physicochemical characterization of PAA/Schizo microgels revealed polymeric spherical particles (288 ± 39 nm) and were deemed stable and negatively charged. The produced microgels are not inherently toxic as cell viability was sustained above 80% when mice splenocytes were exposed to concentrations ranging 10–900 µg/mL. PAA/Schizo microgels were evaluated as antigen delivery nanovehicle by adsorbing bovine serum albumin (BSA); with a loading efficiency of 72% and loading capacity of 362 µg/mg. Overall, intranasally-immunized BALB/c mice showed null IgG or IgA responses against PAA/Schizo microgel-BSA, whereas soluble BSA induced significant humoral responses in systemic and mucosal compartments. Splenocytes proliferation assay upon BSA stimulus revealed positive CD4+ T cells-proliferation response in PAA/Schizo microgels-BSA group. Thus, PAA/Schizo microgels constitute functional antigen delivery vehicles of simple and ecofriendly synthesis. Moreover, the use of cell wall fraction as cross-linker agent provides an alternative use for the generation of high-value products using residual algae biomass from the oil industry. Our data suggests that the PAA/Schizo microgels are potential antigen delivery vehicles for immunotherapy development. [ABSTRACT FROM AUTHOR]

Introduction: Molecular responses in the brains of persons with mild cognitive impairment (MCI), the earliest transitional state between normal aging and early Alzheimer's disease (AD), are poorly understood. Methods: We examined AD‐related neuropathology and transcriptome changes in the neocortex of individuals with MCI relative to controls and temporal responses to the mild hypoxia in mouse brains. Results: Subsets of vascular early response to hypoxia genes were upregulated in MCI prior to the buildup of AD neuropathology. Early activation of pro‐angiogenic hypoxia‐inducible factor signaling in response to mild hypoxia was detected in mouse brains similar to those that were altered in MCI. Protracted responses to hypoxia were characterized by activation of phosphoinositide 3‐kinase (PI3K)‐protein kinase B (Akt)‐the mammalian target of rapamycin (mTOR) pathways in brain microvessel isolates. Discussion: These findings suggest that cerebrovascular remodeling is an important antecedent to the development of dementia and a component of the homeostatic response to reduced oxygen tension in aging prior to the onset of AD. [ABSTRACT FROM AUTHOR]

Introduction: Use of complementary and alternative medicine (CAM) therapies had been described in patients with disabling, chronic and painful conditions; these characteristics define the majority of vascular surgery (VS) entities. A lack of disclosure about CAM use from patients has been universally cited and may impact effective patient–doctor communication. Our primary objective was to describe CAM use, modalities, perceived benefits, safety, and associated factors among adult patients attending a VS outpatient clinic; we additionally explored patient's attitudes about CAM disclosure with their primary vascular surgeon. Methods: This cross-sectional study invited 223 consecutive outpatients to an interview where the ICAM-Q (International Complementary and Alternative Medicine Questionnaire) and the PDRQ-9 (Patient-Doctor Relationship Questionnaire-9 items) were applied. In addition, sociodemographics, vascular disease and treatment-related information, comorbidity, and disease severity characteristics were obtained. Appropriated statistics was used; multiple logistic regression analysis identified factors associated to CAM use. All statistical tests were two-sided, and a p value ≤ 0.05 was considered significant. IRB approval was obtained. Results: Patients recruited were primary females (69%) and had a median age of 65 years (54–75). Most frequent vascular diagnoses were chronic venous insufficiency (36.2%) and peripheral artery disease (26%). There were 104 (46.6%) patients who referred CAM use, primarily self-helped practices (96%), and use of herbal, vitamins, or homeopathic medicines (23.7%). Overall, the majority of the patients perceived CAM modalities helpful and 94.6% denied any adverse event. Female sex (OR: 1.768, 95% CI: 0.997–3.135, p = 0.051) and hospitalization during the previous year (OR: 3.173, 95% CI: 1.492–6.748, p = 0.003) were associated to CAM use. The majority of the patients (77%) agreed about CAM disclosure with their primary vascular surgeon; meanwhile, among CAM users, up to 54.9% did not disclose it, and their main reasons were "Doctor didn't ask" (32%) and "I consider it unnecessary" (16%). The patient–doctor relationship was rated by the patients with high scores. Conclusions: CAM use is frequent and perceived as safe and beneficial among VS outpatients; nonetheless, patients do not disclose CAM use with their primary vascular surgeons, and a wide range of reasons are given by the patients that prevent effective and open communication. [ABSTRACT FROM AUTHOR]

Chagas disease is one of the most important vector-borne diseases in Latin America. Studying the biological parameters of each vector species or subspecies contributes to our understanding of their epidemiologic importance. The aim of our study was to compare the biological parameters and start to estimate the vectorial capacity of Triatoma protracta protracta Ryckman, T. p. nahuatlae Ryckman, and their laboratory hybrids. Specifically, we estimated nine biological parameters to increase knowledge about the potential role of triatomine hybrids in the transmission of T. cruzi to reservoir hosts. Nine biological parameters related to the lifecycle, feeding and defecation patterns, number of females, fecundity, and egg eclosion rates in cohorts of T. p. protracta, T. p. nahuatlae, and their hybrids were evaluated and compared. Eight parameters (exception: number of laid eggs) indicated that T. p. nahuatlae was a potentially effective vector of T. cruzi. Our results showed that the hybrid cohorts had better fitness and could potentially have higher vectorial capacity than the parental cohorts. The outstanding characteristics of the hybrids found in our study could lead to an increase in the epidemiologic risks caused by transmission of T. cruzi to humans. [ABSTRACT FROM AUTHOR]

Chronic mental health problems are common among military veterans who sustained blast-related traumatic brain injuries. The reasons for this association remain unexplained. Male rats exposed to repetitive low-level blast overpressure (BOP) exposures exhibit chronic cognitive and post-traumatic stress disorder (PTSD)-related traits that develop in a delayed fashion. We examined blast-induced alterations on the transcriptome in four brain areas (anterior cortex, hippocampus, amygdala, and cerebellum) across the time frame over which the PTSD-related behavioral phenotype develops. When analyzed at 6 weeks or 12 months after blast exposure, relatively few differentially expressed genes (DEGs) were found. However, longitudinal analysis of amygdala, hippocampus, and anterior cortex between 6 weeks and 12 months revealed blast-specific DEG patterns. Six DEGs (hyaluronan and proteoglycan link protein 1 [Hapln1], glutamate metabotropic receptor 2 [Grm2], purinergic receptor P2y12 [P2ry12], C-C chemokine receptor type 5 [Ccr5], phenazine biosynthesis-like protein domain containing 1 [Pbld1], and cadherin related 23 [Cdh23]) were found altered in all three brain regions in blast-exposed animals. Pathway enrichment analysis using all DEGs or those uniquely changed revealed different transcription patterns in blast versus sham. In particular, the amygdala in blast-exposed animals had a unique set of enriched pathways related to stress responses, oxidative phosphorylation, and mitochondrial dysfunction. Upstream analysis implicated tumor necrosis factor (TNF)α signaling in blast-related effects in amygdala and anterior cortex. Eukaryotic initiating factor eIF4E (EIF4e), an upstream regulator of P2ry12 and Ccr5, was predicted to be activated in the amygdala. Quantitative polymerase chain reaction (qPCR) validated longitudinal changes in two TNFα regulated genes (cathepsin B [Ctsb], Hapln1), P2ry12, and Grm2. These studies have implications for understanding how blast injury damages the brain and implicates inflammation as a potential therapeutic target.

Tauopathies are a heterogeneous group of neurodegenerative disorders that are clinically and pathologically distinct from Alzheimer's disease (AD) having tau inclusions in neurons and/or glia as their most prominent neuropathological feature. BCI-838 (MGS00210) is a group II metabotropic glutamate receptor (mGluR2/3) antagonist pro-drug. Previously, we reported that orally administered BCI-838 improved learning behavior and reduced anxiety in Dutch (APP E693Q ) transgenic mice, a model of the pathological accumulation of Aβ oligomers found in AD. Herein, we investigated effects of BCI-838 on PS19 male mice that express the tauopathy mutation MAPT P301S associated with human frontotemporal lobar degeneration (FTLD). These mice develop an aging-related tauopathy without amyloid accumulation. Mice were divided into three experimental groups: (1) non-transgenic wild type mice treated with vehicle, (2) PS19 mice treated with vehicle and (3) PS19 mice treated with 5 mg/kg BCI-838. Groups of 10-13 mice were utilized. Vehicle or BCI-838 was administered by oral gavage for 4 weeks. Behavioral testing consisting of a novel object recognition task was conducted after drug administration. Two studies were performed beginning treatment of mice at 3 or 7 months of age. One month of BCI-838 treatment rescued deficits in recognition memory in PS19 mice whether treatment was begun at 3 or 7 months of age. These studies extend the potential utility of BCI-838 to neurodegenerative conditions that have tauopathy as their underlying basis. They also suggest an mGluR2/3 dependent mechanism as a basis for the behavioral deficits in PS19 mice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Introduction: Molecular responses in the brains of persons with mild cognitive impairment (MCI), the earliest transitional state between normal aging and early Alzheimer's disease (AD), are poorly understood., Methods: We examined AD-related neuropathology and transcriptome changes in the neocortex of individuals with MCI relative to controls and temporal responses to the mild hypoxia in mouse brains., Results: Subsets of vascular early response to hypoxia genes were upregulated in MCI prior to the buildup of AD neuropathology. Early activation of pro-angiogenic hypoxia-inducible factor signaling in response to mild hypoxia was detected in mouse brains similar to those that were altered in MCI. Protracted responses to hypoxia were characterized by activation of phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt)-the mammalian target of rapamycin (mTOR) pathways in brain microvessel isolates., Discussion: These findings suggest that cerebrovascular remodeling is an important antecedent to the development of dementia and a component of the homeostatic response to reduced oxygen tension in aging prior to the onset of AD., (© 2021 the Alzheimer's Association.)

Background: Cranioplasty is the used method in neurosurgery for repairing cranial bone defects. In our environment, the most widely used material is cryopreserved autologous bone (ABCp)., Objective: A retrospective observational study was proposed in order to analyze complications in patients who underwent decompressive craniectomy for brain trauma, with subsequent cranioplasty with ABCp., Method: Patients who underwent cranioplasties with consecutive ABCp performed at our institution over a four-year period (2016-2019) with subsequent follow-up were included, collecting multiple variables in relation to the appearance of complications., Results: 113 cranioplasties were performed, of which 85.8% (n = 97) were performed with ABCp. Mainly with frontotemporoparietal bone defect (94.84%) performed late (> 3 months) in 91.76%. The complication rate was 16.49%, the most significant being the infection of the surgical site (n = 8, 8.24%), the presence of intracranial hematoma (n = 3, 3.09%) and the reabsorption of the autologous bone (n = 2, 2.06%), meriting surgical management in nine of them (9.27%)., Conclusions: ABCp is a valid and safe option, which meets the basic characteristics to consider it the ideal material, with an acceptable rate of complications, biocompatible, with osteogenic potential, adequate protection of the brain and decrease in surgery costs., (Copyright: © 2022 Permanyer.)