Targeting Myeloperoxidase Ameliorates Gouty Arthritis: A Virtual Screening Success Story.

This study presents a new approach for identifying myeloperoxidase (MPO) inhibitors with strong in vivo efficacy. By combining inhibitor-like rules and structure-based virtual screening, the pipeline achieved a 70% success rate in discovering diverse, nanomolar-potency reversible inhibitors and hypochlorous acid (HOCl) scavengers. Mechanistic analysis identified RL6 as a genuine MPO inhibitor and RL7 as a potent HOCl scavenger. Both compounds effectively suppressed HOCl production in cells and neutrophils, with RL6 showing a superior inhibition of neutrophil extracellular trap release (NETosis). In a gout arthritis mouse model, intraperitoneal RL6 administration reduced edema, peroxidase activity, and IL-1ß levels. RL6 also exhibited oral bioavailability, significantly reducing paw edema when administered orally. This study highlights the efficacy of integrating diverse screening methods to enhance virtual screening success, validating the anti-inflammatory potential of potent inhibitors, and advancing the MPO inhibitor research.

A prospective study of the proteome of equine pre-implantation embryo.

The present study was conducted to investigate the global proteome of 8-day-old equine blastocysts. Follicular dynamics of eight adult mares were monitored by ultrasonography and inseminated 24 h after the detection of a preovulatory follicle. Four expanded blastocysts were recovered, pooled, and subjected to protein extraction and mass spectrometry. Protein identification was conducted based on four database searches (PEAKS, Proteome Discoverer software, SearchGUI software, and PepExplorer). Enrichment analysis was performed using g:Profiler, Panther, and String platforms. After the elimination of identification redundancies among search tools (at three levels, based on identifiers, peptides, and cross-database mapping), 1977 proteins were reliably identified in the samples of equine embryos. Proteomic analysis unveiled robust metabolic activity in the 8-day equine embryo, highlighted by an abundance of proteins engaged in key metabolic pathways like the TCA cycle, ATP biosynthesis, and glycolysis. The prevalence of chaperones among highly abundant proteins suggests that regulation of protein folding, and degradation is a key process during embryo development. These findings pave the way for developing new strategies to improve equine embryo media and optimize in vitro fertilization techniques.

Loss of c-Kit in Endothelial Cells Protects against Hindlimb Ischemia.

BACKGROUND: Critical limb ischemia (CLI) is the end stage of peripheral artery disease (PAD), and around 30% of CLI patients are ineligible for current treatments. The angiogenic benefits of c-Kit have been reported in the ischemia scenario; however, the present study demonstrates the effects of specific endothelial c-Kit signaling in arteriogenesis during hindlimb ischemia. METHODS: We created conditional knockout mouse models that decrease c-Kit (c-Kit VE-Cadherin CreERT2-c-Kit) or its ligand (SCF VE-Cadherin CreERT2-SCF) specifically in endothelial cells (ECs) after tamoxifen treatment. These mice and a control group (wild-type VE-Cadherin CreERT2-WT) were subjected to hindlimb ischemia or aortic crush to evaluate perfusion/arteriogenesis and endothelial barrier permeability, respectively. RESULTS: Our data confirmed the lower gene expression of c-Kit and SCF in the ECs of c-Kit and SCF mice, respectively. In addition, we confirmed the lower percentage of ECs positive for c-Kit in c-Kit mice. Further, we found that c-Kit and SCF mice had better limb perfusion and arteriogenesis compared to WT mice. We also demonstrated that c-Kit and SCF mice had a preserved endothelial barrier after aortic crush compared to WT. CONCLUSIONS: Our data demonstrate the deleterious effects of endothelial SCF/c-Kit signaling on arteriogenesis and endothelial barrier integrity.

Determination of Inhibitory Effect of PKM2 Enzyme and Antitumoral Activity of Novel Coumarin-Naphthoquinone Hybrids.

BACKGROUND: Oral squamous cell carcinoma (OSCC) represents the primary form of oral cancer, posing a significant global health threat. The existing chemotherapy options are accompanied by notable side effects impacting patient treatment adherence. Consequently, the exploration and development of novel substances with enhanced anticancer effects and fewer side effects have become pivotal in the realms of biological and chemical science. OBJECTIVE: This work presents the pioneering examples of naphthoquinone-coumarin hybrids as a new category of highly effective cytotoxic substances targeting oral squamous cell carcinoma (OSCC). METHODS: Given the significance of both naphthoquinones and coumarins as essential pharmacophores/ privileged structures in the quest for anticancer compounds, this study focused on the synthesis and evaluation of novel naphthoquinones/coumarin hybrids against oral squamous cell carcinoma. RESULTS: By several in vitro, in silico, and in vivo approaches, we demonstrated that compound 6e was highly cytotoxic against OSCC cells and several other cancer cell types and was more selective than current chemotherapeutic drugs (carboplatin) and the naphthoquinone lapachol. Furthermore, compound 6e was non-hemolytic and tolerated in vivo at 50 mg/kg with an LD50 of 62.5 mg/kg. Furthermore, compound 6e did not induce apoptosis and cell cycle arrest but led to intracellular vesicle formation with LC3 aggregation in autophagosomes, suggesting an autophagic cell death. Additionally, 6e had a high-affinity potential for PKM2 protein, higher than the known ligands, such as lapachol or shikonin, and was able to inhibit this enzyme activity in vitro. CONCLUSION: We assert that compound 6e shows promise as a potential lead for a novel chemotherapeutic drug targeting OSCC, with potential applicability to other cancer types.

Pharmaceutical innovativeness index: methodological approach for assessing the value of medicines - a case study of oncology drugs.

BACKGROUND: We propose a framework to assess the value of pharmaceutical innovations, with explicit clinical and methodological parameters, based on the therapeutic value and health needs. RESEARCH DESIGN AND METHODS: The study was based on the adaptation of health technology assessment methods documented in the literature, which was applied to a sample of oncological drugs. Difficulties and issues during the application of those tools were identified and addressed to develop a new framework with new and revised domains and clear classification criterion for each domain. Scores were assigned to each level and domain according to their relevance to generate the final score of innovativeness. RESULTS: The Pharmaceutical Innovation Index (PII) includes four domains, two related to clinical and social dimensions - Therapeutic Need and Added Therapeutic Value - and other two about methodological features - Study Design and Quality (risk of bias). The scores combined after assigned to each domain results Index of the Innovativeness of the medicines represents the degree of pharmaceutical innovation. CONCLUSION: This work proposes a transparent methodology with well-defined criteria and script; the algorithm developed with authors' weightings and criteria may be switched to best adjust to other applications, perspective or clinical indications, while keeping the transparency and objectiveness.

Larval and adult morphology of Photuriselliptica Olivier (Coleoptera, Lampyridae) and a Halloweeny case of cave-dwelling firefly larva feeding on bat guano.

The predatory firefly Photuriselliptica is common throughout the Atlantic Forest and has been proposed as a biomonitor due to the species' narrow niche and elevational range. However, the species is only known from adults, and a more effective monitoring of its populations hinges on the lack of knowledge on their immature stages. Recent sampling in ferruginous caves and inserted in other lithologies, on sites in the Atlantic Forest and Cerrado, have led to the capture of firefly larvae later reared to adults in the lab. Firefly larvae have been reported in South American caves before; however, they have only been identified to family due to the adult-biased taxonomy of Lampyridae. Here, we provide an updated diagnosis of Photuriselliptica, describe its immature stages for the first time, and update the distribution of the species. The larvae of Photuriselliptica were observed to interact with guano of several bat species, including that of vampire bats. These observations are consistent with the less specialized feeding preferences of photurine larvae, unlike most other firefly taxa, which specialize in gastropods and earthworms. It is yet unclear whether P.elliptica are cave specialists. However, since its occurrence outside caves remains unknown, protecting cave environments must be considered in conservation strategies for this important biomonitor species.

Air quality modeling in the metropolitan area of São Paulo, Brazil: A review.

Numerous studies have used air quality models to estimate pollutant concentrations in the Metropolitan Area of São Paulo (MASP) by using different inputs and assumptions. Our objectives are to summarize these studies, compare their performance, configurations, and inputs, and recommend areas of further research. We examined 29 air quality modeling studies that focused on ozone (O3) and fine particulate matter (PM2.5) performed over the MASP, published from 2001 to 2023. The California Institute of Technology airshed model (CIT) was the most used offline model, while the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) was the most used online model. Because the main source of air pollution in the MASP is the vehicular fleet, it is commonly used as the only anthropogenic input emissions. Simulation periods were typically the end of winter and during spring, seasons with higher O3 and PM2.5 concentrations. Model performance for hourly ozone is good with half of the studies with Pearson correlation above 0.6 and root mean square error (RMSE) ranging from 7.7 to 27.1 ppb. Fewer studies modeled PM2.5 and their performance is not as good as ozone estimates. Lack of information on emission sources, pollutant measurements, and urban meteorology parameters is the main limitation to perform air quality modeling. Nevertheless, researchers have used measurement campaign data to update emission factors, estimate temporal emission profiles, and estimate volatile organic compounds (VOCs) and aerosol speciation. They also tested different emission spatial disaggregation approaches and transitioned to global meteorological reanalysis with a higher spatial resolution. Areas of research to explore are further evaluation of models' physics and chemical configurations, the impact of climate change on air quality, the use of satellite data, data assimilation techniques, and using model results in health impact studies. This work provides an overview of advancements in air quality modeling within the MASP and offers practical approaches for modeling air quality in other South American cities with limited data, particularly those heavily impacted by vehicle emissions.

Prospective memory instruments for the assessment of children and adolescents: a systematic review.

BACKGROUND: Prospective memory is the ability to engage in an intention to be performed in the future. The main objective of this study was to identify instruments that assess both time-based and event-based prospective memory in children and adolescents and that have the potential to be clinically applicable. METHOD: Three databases (PubMed, Scopus, and PsycINFO) were searched to identify existing PM measures in original articles published until 2022. Literature searches were conducted using the following terms: (prospective memor* OR memor* for intentions) AND (neuropsychological assessment) AND (test* OR instrument* OR questionnaire* OR task*) AND (psychometric properties) AND (child* OR adolescen*). Relevant studies identified in the reference lists were also included in the review. RESULTS: Ten instruments were identified and classified into three categories: (a) test batteries, (b) experimental procedures, and (c) questionnaires. All the instruments identified were described concerning their content and the psychometric properties available. Some of the instruments presented empirical evidence regarding validity and reliability, but no one provided normative data. CONCLUSION: Besides the recent progress regarding studies publishing the development of a variety of novel measures, there are still many limitations surrounding the assessment of PM in the youth population because of the yet incipient psychometric properties presented by the majority of the PM instruments. Recommendations for a gold-standard PM instrument for assessing children and adolescents are provided.

Inflammatory markers changes following acceptance-based behavioral psychotherapy in generalized anxiety disorder patients: Evidence from a randomized controlled trial.

Introduction: Generalized anxiety disorder (GAD) has been associated with elevated levels of C-reactive protein (CRP) and proinflammatory cytokines. Despite robust evidence as an effective treatment for GAD, research on the effects of cognitive-behavioral therapies (CBT) in the inflammatory profile of patients with clinical anxiety has presented mixed results. Objective: The present study aimed to investigate the effect of an acceptance-based behavior therapy (ABBT) on inflammatory biomarkers and their association with anxiety levels in GAD patients in comparison to supportive therapy as an active control. Methods: Peripheral inflammatory biomarkers (CRP, IL-1ß, IL-4, IL-6, IL-10, TNF-α) were measured in 77 GAD patients who participated in a 14-week 10-session randomized clinical trial of group ABBT (experimental, n = 37) or supportive group therapy (ST: active control group, n = 40). Results: The concentrations of IL-1ß decreased in the control group and the concentrations of IL-6 increased in the experimental group from baseline to post-treatment, whereas no difference was identified in IL-4, IL-10, TNF, or CRP. Although anxiety and depression levels decreased in both treatment conditions, no correlation with inflammation markers was found for most clinical and biological variables. A negative correlation between changes in IL-6 and IL-10 and anxiety symptom score changes was identified. Conclusions: The present study results found that a short trial of acceptance-based behavior therapy did not change the proinflammatory profile which may be associated with GAD. Additional research is needed to evaluate the influence of other inflammation-related variables, longer periods of follow-up as well as the effect of supportive therapy on peripheral inflammatory biomarkers in GAD patients.

Seasonal and circadian evaluation of Ageratum conyzoides essential oil and its nematicidal activity against Caenorhabditis elegans.

The aim of this study was to evaluate the circadian and seasonal variation of Ageratum conyzoides essential oil (EO) and its nematicidal effect on the free-living nematode Caenorhabditis elegans as a model for parasitic helminths. For the seasonal study, the plants were collected from January to December 2022, at 6 a.m., and to assess the circadian rhythm, the plants were collected in April (rainy season) and October (dry season), at 6, 9, 12 a.m. and 3 and 6 p.m. The fresh plants were then subjected to hydrodistillation, and their chemical composition was analyzed using gas chromatography coupled with mass spectrometry (GC-MS). The motility test with C. elegans was carried out. The primary constituent of the oils was precocene I (65.97 to 78.42 %, respectively), followed by E-caryophyllene (6.04 to 12.16 %), comprising an average of 79.87 % of the composition throughout the year. The average yields of EOs were slightly higher in the rainy season, at 0.68 %, compared to the dry season, at 0.62 %. High light hours in the rainy season (12 a.m., 0.96 %) and in the dry season (9 a.m., 0.88 %) seem to contribute to higher daily oil yields. It was observed that the variation between the main constituents of A. conyzoides occurs in inverse proportion when analyzing the main classes of compounds present in the oils: chromenes (CH) and sesquiterpene hydrocarbons (SH). And that the month of March had the highest content of E-caryophyllene (12.16 %) when compared to the other months of the year. On the other hand, January and December had the lowest levels of precocene I (65.97 and 66.85 %). The IC50 of the EO of A. conyzoides varied according to the month and time of collection. The EO obtained in January was the most effective against C. elegans, with an IC50 of 0.01 mg/mL. Thus, A. conyzoides EO could be an alternative for nematode control, exhibiting greater efficacy if extracted during specific seasonal periods.

Anti-Obesity Therapeutic Targets Studied In Silico and In Vivo: A Systematic Review.

In the age of information technology and the additional computational search tools and software available, this systematic review aimed to identify potential therapeutic targets for obesity, evaluated in silico and subsequently validated in vivo. The systematic review was initially guided by the research question "What therapeutic targets have been used in in silico analysis for the treatment of obesity?" and structured based on the acronym PECo (P, problem; E, exposure; Co, context). The systematic review protocol was formulated and registered in PROSPERO (CRD42022353808) in accordance with the Preferred Reporting Items Checklist for Systematic Review and Meta-Analysis Protocols (PRISMA-P), and the PRISMA was followed for the systematic review. The studies were selected according to the eligibility criteria, aligned with PECo, in the following databases: PubMed, ScienceDirect, Scopus, Web of Science, BVS, and EMBASE. The search strategy yielded 1142 articles, from which, based on the evaluation criteria, 12 were included in the systematic review. Only seven these articles allowed the identification of both in silico and in vivo reassessed therapeutic targets. Among these targets, five were exclusively experimental, one was exclusively theoretical, and one of the targets presented an experimental portion and a portion obtained by modeling. The predominant methodology used was molecular docking and the most studied target was Human Pancreatic Lipase (HPL) (n = 4). The lack of methodological details resulted in more than 50% of the papers being categorized with an "unclear risk of bias" across eight out of the eleven evaluated criteria. From the current systematic review, it seems evident that integrating in silico methodologies into studies of potential drug targets for the exploration of new therapeutic agents provides an important tool, given the ongoing challenges in controlling obesity.

Efficacy of Continuous Lateral Rotation Therapy in Mechanically Ventilated Critically Ill Adults on Clinical Outcomes.

Background: This PICO-guided systematic review assessed continuous lateral rotation therapy (CLRT) versus conventional position changes in mechanically ventilated critically ill adults, evaluating mortality, intensive care unit (ICU) and hospital stay duration as primary outcomes, and respiratory function, mechanical ventilation duration, pulmonary complications, and adverse events, as secondary outcomes. Methods: A systematic review followed PRISMA criteria (PROSPERO CRD42022384258). Searches spanned databases: MEDLINE/PubMed, EMBASE, Scopus, ScienceDirect, Cochrane, CINAHL and Web of Science, without language or publication year restrictions. Inclusion criteria involved randomized (RCT) and quasi-randomized trials, comparing CLRT (intervention) with conventional position changes (control). Risk of bias and quality of evidence for RCTs were assessed using the Cochrane collaboration and GRADE tools. For the quasi-randomized trials, the ROBINS-I tool was used. Results: In 18 studies with 1.466 participants (intervention, n= 700, 47.7%; control, n= 766, 52.2%), CLRT was predominantly used for prophylactic purposes, with protocols varying from 10 to 24 hours/day. Meta-analysis (16 RCTs) favored CLRT for reduced mechanical ventilation duration (SMD -0.17 days, CI -0.29 to -0.04, p=0.008) and lower nosocomial pneumonia incidence (OR 0.39, CI 0.29 to 0.52, p<0.00001). CLRT showed no significant impact on mortality (OR 1.04, CI 0.80 to 1.34, p= 0.77), ICU stay (SMD -0.11 days, CI -0.25 to 0.02, p= 0.11), hospital stay (SMD -0.10 days, CI -0.31 to 0.11, p= 0.33) and incidence of pressure ulcers (OR 0.73, CI 0,34 to 1.60, p= 0.44). Conclusions: CLRT showed no significant difference in primary outcomes (mortality, ICU, and hospital stay duration) but revealed significant differences in secondary outcomes (consistently reduced nosocomial pneumonia, with a minor effect on MV duration), supported by moderate certainty. Very low certainty for other outcomes highlights the need for current studies in diverse clinical settings and protocols to assess CLRT effectiveness.

Protein fraction from Sesbania virgata (Cav.) Pers. seeds exhibit antioxidant and antifungal activities.

Sesbania virgata (Cav.) Pers. seeds are protein sources with health and environmental benefits. In this research, proteins with lectin activity were identified in a protein fraction from S. virgata seeds (PFLA), as well its antioxidant and antimicrobial potentials, in addition to cytotoxic effects. To obtain PFLA, seed flour was homogenized in Glycine-NaOH (100 mM; pH 9.0; NaCl 150 mM) and precipitated in ammonium sulfate. PFLA concentrates bioactive lectins (32 HU/mL, 480 HU/gFa, 18.862 HU/mgP) and essential amino acids (13.36 g/100g protein). PFLA exerts antioxidant activity, acting as a promising metal chelating agent (~77% of activity). Analyzes of cell culture assay results suggest that antioxidant activity of PFLA may be associated with the recruitment of essential molecules to prevent the metabolic impairment of cells exposed to oxidative stress. PFLA (256 - 512 µg/mL) also exhibits antifungal activity, inhibiting the growth of Aspergillus flavus, Candida albicans, Candida tropicalis and Penicillium citrinum. Cytotoxic analysis indicates a tendency of low interference in the proliferation of 3T3 and HepG2 cells in the range of PFLA concentrations with biological activity. These findings support the notion that PFLA is a promising adjuvant to be applied in current policies on the management of metal ion chelation and fungal infections.

Statine-based peptidomimetic compounds as inhibitors for SARS-CoV-2 main protease (SARS-CoV­2 Mpro).

COVID-19 is a multisystemic disease caused by the SARS-CoV-2 airborne virus, a member of the Coronaviridae family. It has a positive sense single-stranded RNA genome and encodes two non-structural proteins through viral cysteine-proteases processing. Blocking this step is crucial to control virus replication. In this work, we reported the synthesis of 23 statine-based peptidomimetics to determine their ability to inhibit the main protease (Mpro) activity of SARS-CoV-2. Among the 23 peptidomimetics, 15 compounds effectively inhibited Mpro activity by 50% or more, while three compounds (7d, 8e, and 9g) exhibited maximum inhibition above 70% and IC50 < 1 µM. Compounds 7d, 8e, and 9g inhibited roughly 80% of SARS-CoV-2 replication and proved no cytotoxicity. Molecular docking simulations show putative hydrogen bond and hydrophobic interactions between specific amino acids and these inhibitors. Molecular dynamics simulations further confirmed the stability and persisting interactions in Mpro's subsites, exhibiting favorable free energy binding (ΔGbind) values. These findings suggest the statine-based peptidomimetics as potential therapeutic agents against SARS-CoV-2 by targeting Mpro.

Changes in eating habits and lifestyle during the first year of the COVID-19 pandemic across metropolitan regions in Brazil and Germany: A survey-based cross-sectional study.

COVID-19 caused profound societal changes to cope rapidly with the new circumstances. The food market changed its quantity, quality, form, and frequency dynamics. Consequently, food-eating habits and lifestyles like physical exercise likely experienced changes. An online-based survey was conducted between June 2020 and January 2021 in the metropolitan regions of Rhine Ruhr Metropolis (RRM), Greater São Paulo (GSP), other metropolitan regions in São Paulo state (oMRSP), other Brazilian metropolitan regions (oBRMR), and the remaining urban areas in both countries (oUA), representing different contexts of Brazil and Germany. We assessed self-reported changes in physical activity level, diet quality, self-reported eating habits, and buying groceries during the first year of the pandemic. In Germany, indoor and outdoor activities increased for 34% of the respondents, while in Brazil, there was a decrease in physical activity for 50% of the participants. The Healthy Eating Index (HEI) scored higher among Brazilians (16.8) than Germans (15.2) on a 0-29 HEI scale. Increased awareness of healthy and sustainable eating habits was observed in GSP (0.7), oMRSP (0.63), oBRMR (0.7), and oUA (0.68) on a scale from no change (0) to change (1). In RRM, an increase in convenience foods was noticed (0.86). Participants reported discomfort with food purchasing due to hygiene measures and avoided going to the supermarket (0.7 on average in Brazil and 0.58 for females using the same 0-1 scale). Also, food supply at the grocery shops was reported to be often unavailable and in lower quantities. A real-time assessment of self-reported changes in eating habits and lifestyle during the lockdown in 2020 in different contexts is insightful for rethinking strategies to improve conditions in the post-COVID-19 era and prepare for future pandemics.

Synthesis of lignin-based carbon/graphene oxide foam and its application as sensors for ammonia gas detection.

The present study highlights the integration of lignin with graphene oxide (GO) and its reduced form (rGO) as a significant advancement within the bio-based products industry. Lignin-phenol-formaldehyde (LPF) resin is used as a carbon source in polyurethane foams, with the addition of 1 %, 2 %, and 4 % of GO and rGO to produce carbon structures thus producing carbon foams (CFs). Two conversion routes are assessed: (i) direct addition with rGO solution, and (ii) GO reduction by heat treatment. Carbon foams are characterized by thermal, structural, and morphological analysis, alongside an assessment of their electrochemical behavior. The thermal decomposition of samples with GO is like those having rGO, indicating the effective removal of oxygen groups in GO by carbonization. The addition of GO and rGO significantly improved the electrochemical properties of CF, with the GO2% sensors displaying 39 % and 62 % larger electroactive area than control and rGO2% sensors, respectively. Furthermore, there is a significant electron transfer improvement in GO sensors, demonstrating a promising potential for ammonia detection. Detailed structural and performance analysis highlights the significant enhancement in electrochemical properties, paving the way for the development of advanced sensors for gas detection, particularly ammonia, with the prospective market demands for durable, simple, cost-effective, and efficient devices.

Co3O4/activated carbon nanocomposites as electrocatalysts for the oxygen evolution reaction.

The Oxygen Evolution Reaction (OER) is crucial in various processes such as hydrogen production via water splitting. Several electrocatalysts, including metal oxides, have been evaluated to enhance the reaction efficiency. Zeolitic Imidazolate Framework-67 (ZIF-67) has been employed as a precursor to produce Co3O4, showing high OER activity. Additionally, the formation of composites with carbon-based materials improves the activity of these materials. Thus, this work focuses on synthesizing ZIF-67 and commercial activated carbon (AC) composites, which were used as precursors to obtain Co3O4/C electrocatalysts by calculating ZIF-67/CX (X = 10, 30, and 50, the mass percentage of AC). The obtained materials were thoroughly characterized by employing X-ray powder diffraction (XRD), confirming the cobalt oxide structure with a sphere-like morphology as observed in the TEM images. The presence of oxygen vacancies was confirmed by infrared spectroscopy and EPR measurements. The electrocatalytic performance in the OER was investigated by linear sweep voltammetry (LSV), which revealed an overpotential of 325 mV at 10 mA cm-2 and a Tafel slope value of 65.32 mV dec-1 for Co3O4/C10, superior in activity to several previously reported studies in the literature and electrochemical stability of up to 8 hours. The reduced value of charge transfer resistance, high double-layer capacitance, and the presence of Co3+ ions justify the superior performance of the Co3O4/C10 electrocatalyst.

Posterior circulation collaterals as predictors of outcome in basilar artery occlusion: a sub-analysis of the BASICS randomized trial.

Introduction and purpose: Basilar artery occlusion (BAO) is still one of the most devastating neurological conditions associated with high morbidity and mortality. In the present study, we aimed to assess the role of posterior circulation collaterals as predictors of outcome in the BASICS trial and to compare two grading systems (BATMAN score and PC-CS) in terms of prognostic value. Methods: We performed a sub-analysis of the BASICS trial. Baseline clinical and imaging variables were analyzed. For the imaging analysis, baseline CT and CTA were analyzed by a central core lab. Only those patients with good or moderate quality of baseline CTA and with confirmed BAO were included. Multivariable binary logistic regression analysis was used to test the independent association of clinical and imaging characteristics with a favorable outcome at 3 months (defined as a modified Rankin Score of ≤3). ROC curve analysis was used to assess and compare accuracy between the two collateral grading systems. Results: The mean age was 67.0 (±12.5) years, 196 (65.3%) patients were males and the median NIHSS was 21.5 (IQR 11-35). Median NCCT pc-ASPECTS was 10 (IQR10-10) and median collateral scores for BATMAN and PC-CS were 8 (IQR 7-9) and 7 (IQR 6-8) respectively. Collateral scores were associated with favorable outcome at 3 months for both BATMAN and PC-CS but only with a modest accuracy on ROC curve analysis (AUC 0.62, 95% CI [0.55-0.69] and 0.67, 95% CI [0.60-0.74] respectively). Age (OR 0.97, 95% CI [0.95-1.00]), NIHSS (OR 0.91, 95% CI [0.89-0.94]) and collateral score (PC-CS - OR 1.2495% CI [1.02-1.51]) were independently associated with clinical outcome. Conclusion: The two collateral grading systems presented modest prognostic accuracy. Only the PC-CS was independently associated with a favorable outcome at 3 months.

Structural Characterization and Rat Aortic Vascular Reactivity of Bradykinin-Potentiating Peptides (BPPs) from the Snake Venom of Bothrops moojeni from Delta do Parnaíba Region, Brazil.

Snake venoms contain various bradykinin-potentiating peptides (BPPs). First studied for their vasorelaxant properties due to angiotensin converting enzyme (ACE) inhibition, these molecules present a range of binding partners, among them the argininosuccinate synthase (AsS) enzyme. This has renewed interest in their characterization from biological sources and the evaluation of their pharmacological activities. In the present work, the low molecular weight fraction of Bothrops moojeni venom was obtained and BPPs were characterized by mass spectrometry. Eleven BPPs or related peptides were sequenced, and one of them, BPP-Bm01, was new. Interestingly, some oxidized BPPs were detected. The three most abundant peptides were BPP-Bm01, BPP-Bax12, and BPP-13a, and their putative interactions with the AsS enzyme were investigated in silico. A binding cavity for these molecules was predicted, and docking studies allowed their ranking. Three peptides were synthesized and submitted to vasorelaxation assays using rat aortic rings. While all BPPs were active, BPP-Bm01 showed the highest potency in this assay. This work adds further diversity to BPPs from snake venoms and suggests, for the first time, a putative binding pocket for these molecules in the AsS enzyme. This can guide the design of new and more potent AsS activators.