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1.
J Neurointerv Surg ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39019504

RESUMO

BACKGROUND: Carotid web (CaW)-related contrast stagnation on digital subtraction angiography (DSA) may be a marker supporting the pathophysiological theory of stasis and thrombosis/embolization. We aim to assess the correlation between DSA hemodynamic parameters with CT angiography (CTA) structural measurements and clinical characteristics. METHODS: Cross-sectional analysis of consecutive patients with CaW who underwent CTA+DSA. DSA-derived hemodynamic parameters were calculated based on a region of interest at the carotid bulb (time-density curves; TDC). The correlation between duration of contrast stagnation with CaW structural features and with clinical characteristics was evaluated with a mixed effects model. RESULTS: Sixty patients of mean±SD age 52.2±10.3 years were included, of whom 38 (63.3%) were women, 51 (85%) were black, and 59 (98.3%) had symptomatic lesions. The median CaW base was 2.46 mm (range 1.95-3.76), length 2.7 mm (range 2.15-3.96), thickness (length/base) 1.05 (IQR 0.81-1.36), caudal angle 31.93° (IQR 22.35-43.58), mean±SD distal angle 66.91±15.84°, pocket area 1.62 mm² (0.96-1.62), and pocket perimeter 6.03±2.6 mm. The TDC consistently showed an initial fast decay from the peak concentration followed by a plateau with a negative exponential pattern. The median stagnation time from peak density to 80% contrast clearance was 2.91 s (range 1.81-4.94). No significant associations were observed between the stagnation time and CaW CTA structural measurements (length/base/thickness, caudal and cranial angles web surface angles, web pocket area/perimeter) or clinical characteristics. CONCLUSIONS: A negative exponential pattern in the DSA contrast clearance of the CaW pocket was observed. There were no morphological or clinical features clearly associated with the duration of contrast stagnation on DSA. The hemodynamic disruption caused by CaW and its thrombotic risk may not be appropriately measured by contrast stagnation time.

2.
Sci Total Environ ; : 174745, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39032754

RESUMO

Harmful cyanobacterial blooms will be more intense and frequent in the future, contaminating surface waters with cyanotoxins and posing a threat to communities heavily reliant on surface water usage for crop irrigation. Constructed wetlands (CWs) are proposed to ensure safe crop irrigation, but more research is needed before implementation. The present study operated 28 mesocosms in continuous mode mimicking horizontal sub-surface flow CWs. Mesocosms were fed with synthetic lake water and spiked periodically with two cyanotoxins, microcystin-LR (MC-LR) and cylindrospermopsin (CYN), at environmentally relevant cyanotoxins concentrations (10 µg L-1). The influence of various design factors, including plant species, porous media, and seasonality, was explored. The mesocosms achieved maximum MC-LR and CYN mass removal rates of 95 % and 98 %, respectively. CYN removal is reported for the first time in CWs mimicking horizontal sub-surface flow CWs. Planted mesocosms consistently outperformed unplanted mesocosms, with Phragmites australis exhibiting superior cyanotoxin mass removal compared to Juncus effusus. Considering evapotranspiration, J. effusus yielded the least cyanotoxin-concentrated effluent due to the lower water losses in comparison with P. australis. Using the P-kC* model, different scaling-up scenarios for future piloting were calculated and discussed. Additionally, bacterial community structure was analyzed through correlation matrices and differential taxa analyses, offering valuable insights into their removal of cyanotoxins. Nevertheless, attempts to validate microcystin-LR biotransformation via the known mlrA gene degradation pathway were unfruitful, indicating alternative enzymatic degradation pathways occurring in such complex CW systems. Further investigation into the precise molecular mechanisms of removal and the identification of transformation products is needed for the comprehensive understanding of cyanotoxin mitigation in CW. This study points towards the feasibility of horizontal sub-surface flow CWs to be employed to control cyanotoxins in irrigation or recreational waters.

3.
Interv Neuroradiol ; : 15910199241262844, 2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39034141

RESUMO

BACKGROUND: The eThrombolysis in Cerebral Infarction (eTICI) score has been validated in proximal large artery occlusion (pLAOs). Despite the growing number of distal medium vessel occlusions (DMVOs) mechanical thrombectomies (MT) and the widespread utilization of the eTICI scoring system, its reliability and standardization for more distal occlusions have not been validated. We aim to evaluate the interrater reliability of eTICI scores in primary DMVOs. METHODS: This was a retrospective analysis of a prospectively maintained database for consecutive patients with pLAO and DMVO MT at a single comprehensive stroke center from 2015 to 2022. Two fellowship-trained neurointerventionalists blindly/independently assessed digital subtraction angiograms for final eTICI, followed by consensus reads for discrepancies. RESULTS: 59 DMVO of 2248 thrombectomies [M3:29(50%)/M4:1(2%)/A1:3(5%)/A2:12(22%)/A3: 5(9%)/P1:7(12%)/P2:1(2%)] and 124 pLAOs of 308 thrombectomies [i-ICA:13(11%)/MCA-M1: 111(90%)] were included. The distribution of final eTICI scores was comparable between pLAO vs DMVOs (p = 0.82). The pLAO final eTICI score assessment between two readers demonstrated moderate reliability with a kappa0.77 (95%CI: 0.67-0.88), while the DMVO eTICI score assessment exhibited almost-perfect agreement with kappa 0.94 (95%CI: 0.90-0.99). The agreement between the consensus read and the original report in DMVOs was 0.86 (95% CI: 0.71-1.00) while for pLAO it was 0.83(95% CI: 0.76-0.90). The performance of eTICI was comparable amongst different DMVO territories as well as for distal vs. very distal occlusions. CONCLUSION: eTICI score exhibited comparable performance for DMVO as compared to pLAO strokes. Further studies investigating DMVO eTICI grading and clinical outcomes are warranted.

4.
Mar Drugs ; 22(6)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38921579

RESUMO

Bioprospecting the secondary metabolism of underexplored Actinomycetota taxa is a prolific route to uncover novel chemistry. In this work, we report the isolation, structure elucidation, and bioactivity screening of cellulamides A and B (1 and 2), two novel linear peptides obtained from the culture of the macroalga-associated Cellulosimicrobium funkei CT-R177. The host of this microorganism, the Chlorophyta Codium tomentosum, was collected in the northern Portuguese coast and, in the scope of a bioprospecting study focused on its associated actinobacterial community, strain CT-R177 was isolated, taxonomically identified, and screened for the production of antimicrobial and anticancer compounds. Dereplication of a crude extract of this strain using LC-HRMS(/MS) analysis unveiled a putative novel natural product, cellulamide A (1), that was isolated following mass spectrometry-guided fractionation. An additional analog, cellulamide B (2) was obtained during the chromatographic process and chemically characterized. The chemical structures of the novel linear peptides, including their absolute configurations, were elucidated using a combination of HRMS, 1D/2D NMR spectroscopy, and Marfey's analysis. Cellulamide A (1) was subjected to a set of bioactivity screenings, but no significant biological activity was observed. The cellulamides represent the first family of natural products reported from the Actinomycetota genus Cellulosimicrobium, showcasing not only the potential of less-explored taxa but also of host-associated marine strains for novel chemistry discovery.


Assuntos
Peptídeos , Humanos , Peptídeos/química , Peptídeos/farmacologia , Peptídeos/isolamento & purificação , Actinobacteria/química , Actinobacteria/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Organismos Aquáticos , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Linhagem Celular Tumoral , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação
5.
Nat Microbiol ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862603

RESUMO

Dimethylsulfoniopropionate (DMSP) is an abundant marine organosulfur compound with roles in stress protection, chemotaxis, nutrient and sulfur cycling and climate regulation. Here we report the discovery of a bifunctional DMSP biosynthesis enzyme, DsyGD, in the transamination pathway of the rhizobacterium Gynuella sunshinyii and some filamentous cyanobacteria not previously known to produce DMSP. DsyGD produces DMSP through its N-terminal DsyG methylthiohydroxybutyrate S-methyltransferase and C-terminal DsyD dimethylsulfoniohydroxybutyrate decarboxylase domains. Phylogenetically distinct DsyG-like proteins, termed DSYE, with methylthiohydroxybutyrate S-methyltransferase activity were found in diverse and environmentally abundant algae, comprising a mix of low, high and previously unknown DMSP producers. Algae containing DSYE, particularly bloom-forming Pelagophyceae species, were globally more abundant DMSP producers than those with previously described DMSP synthesis genes. This work greatly increases the number and diversity of predicted DMSP-producing organisms and highlights the importance of Pelagophyceae and other DSYE-containing algae in global DMSP production and sulfur cycling.

6.
Sci Total Environ ; 946: 174273, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-38925380

RESUMO

This comprehensive scientific review evaluates the effectiveness of nature-based solutions (NBS) in reducing antibiotics (ABs), combating antimicrobial resistance (AMR), and controlling pathogens in various aquatic environments at different river catchment levels. It covers conventional and innovative treatment wetland configurations for wastewater treatment to reduce pollutant discharge into the aquatic ecosystems as well as exploring how river restoration and saltmarshes can enhance pollutant removal. Through the analysis of experimental studies and case examples, the review shows NBS's potential for providing sustainable and cost-effective solutions to improve the health of aquatic ecosystems. It also evaluates the use of diagnostic indicators to predict NBS effectiveness in removing specific pollutants such as ABs and AMR. The review concludes that NBS are feasible for addressing the new challenges stemming from human activities such as the presence of ABs, AMR and pathogens, contributing to a better understanding of NBS, highlighting success stories, addressing knowledge gaps, and providing recommendations for future research and implementation.


Assuntos
Antibacterianos , Ecossistema , Áreas Alagadas , Resistência Microbiana a Medicamentos , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/análise , Águas Residuárias/microbiologia , Rios/microbiologia , Rios/química
7.
Anal Chim Acta ; 1311: 342657, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38816150

RESUMO

BACKGROUND: The latest chromatographic retention models are capable of accurately describe the dependencies of retention over a wide range of experimental conditions. By using a suitable conversion, these models can be transformed into equations expressing the optimization criteria as function of multiples variables. Even though that theoretical models significantly reduce the experimental requirements for optimizations, these models have been barely used. Instead, most optimizations rely on empirical exploration of the relationships between criterions and variables. There is a need for a strategy to reduce the required number of experiments in multivariated optimization of separations, and Fundamental Models offer a clear opportunity for addressing it. RESULTS: A Fundamental Model is used to give the simultaneous dependence of chromatographic retention of seven ionizable pesticides on the three variables: solvent composition, temperature and pH (w, T, pH). Based on few experiments, the 10 parameters required to predict the chromatographic retention of those compounds, taken as model analytes, can be obtained. Two mathematical treatments to convert retentions into resolutions between pairs are used: one considering extracolumn dispersions and other neglecting these contributions. Using the Overlapped Resolutions Maps, extended to four dimensions, two optimal conditions can be found for the two different mathematical conversions. Chromatographic conditions were empirically evaluated obtaining the best results for the optimization considering extracolumn dispersions, proving that this condition is a true optimal. It was demonstrated that any small shift in any of the variables from this true optimal leads to a loss in resolution. SIGNIFICANCE: Fundamental Models describing chromatographic retention as a simultaneous function of multiple variables are nowadays very accurate. In this work is demonstrated that these models are useful not only to predict retentions, but also to optimize separations, even in the more challenging mode: isocratic, isothermal and iso-pH. However, the success in the optimization procedure depends also on the proper definition of the mathematical conversion of the Fundamental Models into optimization criteria.

8.
J Hypertens ; 42(7): 1173-1183, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38690885

RESUMO

OBJECTIVE: To evaluate the effectiveness of a nutritional strategy based on two components and adapted for the public health system on blood pressure, cardiometabolic features, self-care, qualify of life and diet quality in individuals with hypertension. METHODS: NUPRESS was an open-label, parallel-group, superiority randomized controlled clinical trial in which participants at least 21 years with hypertension and poorly controlled blood pressure were randomly assigned (1 : 1 allocation ratio) to either an individualized dietary prescription according to nutritional guidelines (control group, n  = 205); or a two-component nutrition strategy, including a goal-directed nutritional counseling and mindfulness techniques (NUPRESS [intervention] group, n  = 205). Primary outcomes were SBP (mmHg) after 24 weeks of follow up and blood pressure control, defined as either having SBP more than 140 mmHg at baseline and achieving 140 mmHg or less after follow-up or having SBP 140 mmHg or less at baseline and reducing the frequency of antihypertensive drugs in use after follow-up. RESULTS: In total, 410 participants were randomized and submitted to an intention-to-treat analysis regarding primary outcomes. Both groups decreased blood pressure, but after adjusting for baseline values, there was no significant difference between them on SBP [intervention-control difference: -0.03 (-3.01; 2.94); P  = 0.98] nor blood pressure control [odds ratio 1.27 (0.82; 1.97); P  = 0.28]. No differences between groups were also detected regarding secondary and tertiary outcomes. CONCLUSION: There was no difference between a two-component nutritional strategy and an established dietary intervention on blood pressure in participants with hypertension.


Assuntos
Pressão Sanguínea , Hipertensão , Humanos , Hipertensão/dietoterapia , Hipertensão/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Adulto , Saúde Pública , Anti-Hipertensivos/uso terapêutico
9.
Stroke ; 55(6): 1489-1497, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38787927

RESUMO

BACKGROUND: Endovascular treatment (EVT) is part of the usual care for proximal vessel occlusion strokes. However, the safety and effectiveness of EVT for distal medium vessel occlusions remain unclear. We sought to compare the clinical outcomes of EVT to medical management (MM) for isolated distal medium vessel occlusions. METHODS: This is a retrospective analysis of prospectively collected data from seven comprehensive stroke centers. Patients were included if they had isolated distal medium vessel occlusion strokes due to middle cerebral artery M3/M4, anterior cerebral artery A2/A3, or posterior cerebral artery P1/P2 segments. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included 90-day good (mRS score, 0-2) and excellent (mRS score, 0-1) outcomes. Safety measures included symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: A total of 321 patients were included in the analysis (EVT, 179; MM, 142; 40.8% treated with intravenous thrombolysis). In the inverse probability of treatment weighting model, there were no significant differences between EVT and MM in terms of the overall degree of disability (mRS ordinal shift; adjusted odds ratio [aOR], 1.25 [95% CI, 0.95-1.64]; P=0.110), rates of good (mRS score, 0-2; aOR, 1.32 [95% CI, 0.97-1.80]; P=0.075) and excellent (aOR, 1.32 [95% CI, 0.94-1.85]; P=0.098) outcomes, or mortality (aOR, 1.20 [95% CI, 0.78-1.85]; P=0.395) at 90 days. The multivariable regression model showed similar findings. Moreover, there was no difference between EVT and MM in rates of symptomatic intracranial hemorrhage in the multivariable regression model (aOR, 0.57 [95% CI, 0.21-1.58]; P=0.277), but the inverse probability of treatment weighting model showed a lower likelihood of symptomatic intracranial hemorrhage (aOR, 0.46 [95% CI, 0.24-0.85]; P=0.013) in the EVT group. CONCLUSIONS: This multicenter study failed to demonstrate any significant outcome differences among patients with isolated distal medium vessel occlusions treated with EVT versus MM. These findings reinforce clinical equipoise. Randomized clinical trials are ongoing and will provide more definite evidence.


Assuntos
Procedimentos Endovasculares , Humanos , Masculino , Feminino , Procedimentos Endovasculares/métodos , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Idoso de 80 Anos ou mais , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/cirurgia , Terapia Trombolítica/métodos , Infarto da Artéria Cerebral Média/cirurgia , AVC Isquêmico/cirurgia , AVC Isquêmico/terapia
10.
Antibiotics (Basel) ; 13(5)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38786156

RESUMO

Bacterial infections and resistance to antibiotic drugs represent the highest challenges to public health. The search for new and promising compounds with anti-bacterial activity is a very urgent matter. To promote the development of platforms enabling the discovery of compounds with anti-bacterial activity, Fourier-Transform Mid-Infrared (FT-MIR) spectroscopy coupled with machine learning algorithms was used to predict the impact of compounds extracted from Cynara cardunculus against Escherichia coli. According to the plant tissues (seeds, dry and fresh leaves, and flowers) and the solvents used (ethanol, methanol, acetone, ethyl acetate, and water), compounds with different compositions concerning the phenol content and antioxidant and antimicrobial activities were obtained. A principal component analysis of the spectra allowed us to discriminate compounds that inhibited E. coli growth according to the conventional assay. The supervised classification models enabled the prediction of the compounds' impact on E. coli growth, showing the following values for accuracy: 94% for partial least squares-discriminant analysis; 89% for support vector machine; 72% for k-nearest neighbors; and 100% for a backpropagation network. According to the results, the integration of FT-MIR spectroscopy with machine learning presents a high potential to promote the discovery of new compounds with antibacterial activity, thereby streamlining the drug exploratory process.

11.
Sci Transl Med ; 16(747): eadl4497, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748771

RESUMO

Endovascular interventions are increasingly becoming the preferred approach for treating strokes and cerebral artery diseases. These procedures rely on sophisticated angiographical imaging guidance, which encounters challenges because of limited contrast and spatial resolution. Achieving a more precise visualization of the underlying arterial pathology and neurovascular implants is crucial for accurate procedural decision-making. In a human study involving 32 patients, we introduced the clinical application of a miniaturized endovascular neuro optical coherence tomography (nOCT) imaging probe. This technology was designed to navigate the tortuous paths of the cerebrovascular circulation and to offer high-resolution imaging in situ. The nOCT probe is compatible with standard neurovascular microcatheters, integrating with the procedural workflow used in clinical routine. Equipped with a miniaturized optical fiber and a distal lens, the probe illuminates the tissue and collects the backscattered, near-infrared light. While rotating the fiber and the lens at high speed, the probe is rapidly retracted, creating a spiral-shaped light pattern to comprehensively capture the arterial wall and implanted devices. Using nOCT, we demonstrated volumetric microscopy of cerebral arteries in patients undergoing endovascular procedures. We imaged the anterior and posterior circulation of the brain, including distal segments of the internal carotid and middle-cerebral arteries, as well as the vertebral, basilar, and posterior cerebral arteries. We captured a broad spectrum of neurovascular pathologies, such as brain aneurysms, ischemic stroke, arterial stenoses, dissections, and intracranial atherosclerotic disease. nOCT offered artifact-free, high-resolution visualizations of intracranial artery pathology and neurovascular devices.


Assuntos
Artérias Cerebrais , Tomografia de Coerência Óptica , Tomografia de Coerência Óptica/métodos , Humanos , Artérias Cerebrais/diagnóstico por imagem , Microscopia/métodos , Miniaturização , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/métodos
12.
Mil Med ; 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38771104

RESUMO

INTRODUCTION: During the novel coronavirus disease 2019 pandemic, health care workers experienced facial problems from prolonged use of N95 masks, including skin irritation, pigmentation changes, and contact dermatitis. We assessed the use of hydrocolloid dressing versus dimethicone cream to prevent skin breakdown among military health care workers while wearing an N95. MATERIALS AND METHODS: Participants were recruited using convenience and snowball sampling in this nonblinded, randomized, cross-over study with 2 active treatments, hydrocolloid dressing and dimethicone cream, across 3 time points. The skin was assessed using photographs and subepidermal moisture scanner (SEM). N95 seal integrity was assessed using qualitative fit test. Institutional review board approval was obtained from the Madigan Army Medical Center Institutional Review Board. RESULTS: Among the 73 participants, wearing an N95 alone versus with dimethicone cream or hydrocolloid dressing caused more adverse skin reactions. There were no significant differences in qualitative fit test failure rate between groups. Participants experienced minimal to no dizziness, loss of energy/tiredness/fatigue, claustrophobia, shortness of breath, difficulty breathing, and dry or itchy eyes. For all interventions, wearing an N95 did not interfere with participants' concentration, verbal communication, hearing, vision, and, importantly, delivery of care. CONCLUSIONS: Using a skin protectant with an N95 may prevent adverse skin reactions while preserving health care workers' ability to safely and competently care for patients in routine and pandemic conditions.

13.
J Neurointerv Surg ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38782568

RESUMO

BACKGROUND: Early identification of intracranial atherosclerotic disease (ICAD) may impact the management of patients undergoing mechanical thrombectomy (MT). We sought to develop and validate a scoring system for pre-thrombectomy diagnosis of ICAD in anterior circulation large vessel/distal medium vessel occlusion strokes (LVOs/DMVOs). METHODS: Retrospective analysis of two prospectively maintained comprehensive stroke center databases including patients with anterior circulation occlusions spanning 2010-22 (development cohort) and 2018-22 (validation cohort). ICAD cases were matched for age and sex (1:1) to non-ICAD controls. RESULTS: Of 2870 MTs within the study period, 348 patients were included in the development cohort: 174 anterior circulation ICAD (6% of 2870 MTs) and 174 controls. Multivariable analysis ß coefficients led to a 20 point scale: absence of atrial fibrillation (5); vascular risk factor burden (1) for each of hypertension, diabetes, smoking, and hyperlipidemia; multifocal single artery stenoses on CT angiography (3); absence of territorial cortical infarct (3); presence of borderzone infarct (3); or ipsilateral carotid siphon calcification (2). The validation cohort comprised 56 ICAD patients (4.1% of 1359 MTs): 56 controls. Area under the receiver operating characteristic curve was 0.88 (0.84-0.91) and 0.82 (0.73-0.89) in the development and validation cohorts, respectively. Calibration slope and intercept showed a good fit for the development cohort although with overestimated risk for the validation cohort. After intercept adjustment, the overestimation was corrected (intercept 0, 95% CI -0.5 to -0.5; slope 0.8, 95% CI 0.5 to 1.1). In the full cohort (n=414), ≥11 points showed the best performance for distinguishing ICAD from non-ICAD, with 0.71 (95% CI 0.65 to 0.78) sensitivity and 0.82 (95% CI 0.77 to 0.87) specificity, and 3.92 (95% CI 2.92 to 5.28) positive and 0.35 (95% CI 0.28 to 0.44) negative likelihood ratio. Scores ≥12 showed 90% specificity and 63% sensitivity. CONCLUSION: The proposed scoring system for preprocedural diagnosis of ICAD LVOs and DMVOs presented satisfactory discrimination and calibration based on clinical and non-invasive radiological data.

14.
Biotechnol Bioeng ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760962

RESUMO

To robustly discover and explore phytocompounds, it is necessary to evaluate the interrelationships between the plant species, plant tissue, and the extraction process on the extract composition and to predict its cytotoxicity. The present work evaluated how Fourier Transform InfraRed spectroscopy can acquire the molecular profile of aqueous and ethanol-based extracts obtained from leaves, seeds, and flowers of Cynara Cardunculus, and ethanol-based extracts from Matricaria chamomilla flowers, as well the impact of these extracts on the viability of mammalian cells. The extract molecular profile enabled to predict the extraction yield, and how the plant species, plant tissue, and extraction process affected the extract's relative composition. The molecular profile obtained from the culture media of cells exposed to extracts enabled to capture its impact on cells metabolism, at a higher sensitivity than the conventional assay used to determine the cell viability. Furthermore, it was possible to detect specific impacts on the cell's metabolism according to plant species, plant tissue, and extraction process. Since spectra were acquired on small volumes of samples (25 µL), after a simple dehydration step, and based on a plate with 96 wells, the method can be applied in a rapid, simple, high-throughput, and economic mode, consequently promoting the discovery of phytocompounds.

15.
Toxics ; 12(4)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38668486

RESUMO

Acute intoxication with organophosphorus (OP) cholinesterase inhibitors can produce seizures that rapidly progress to life-threatening status epilepticus. Significant research effort has been focused on investigating the involvement of muscarinic acetylcholine receptors (mAChRs) in OP-induced seizure activity. In contrast, there has been far less attention on nicotinic AChRs (nAChRs) in this context. Here, we address this data gap using a combination of in vitro and in vivo models. Pharmacological antagonism and genetic deletion of α4, but not α7, nAChR subunits prevented or significantly attenuated OP-induced electrical spike activity in acute hippocampal slices and seizure activity in mice, indicating that α4 nAChR activation is necessary for neuronal hyperexcitability triggered by acute OP exposures. These findings not only suggest that therapeutic strategies for inhibiting the α4 nAChR subunit warrant further investigation as prophylactic and immediate treatments for acute OP-induced seizures, but also provide mechanistic insight into the role of the nicotinic cholinergic system in seizure generation.

16.
Front Pharmacol ; 15: 1347485, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38576493

RESUMO

Bioprospecting actinobacterial secondary metabolism from untapped marine sources may lead to the discovery of biotechnologically-relevant compounds. While studying the diversity and bioactive potential of Actinomycetota associated with Codium tomentosum, a green seaweed collected in the northern Portuguese cost, strain CT-F61, identified as Streptomyces violaceoruber, was isolated. Its extracts displayed a strong anticancer activity on breast carcinoma T-47D and colorectal carcinoma HCT116 cells, being effective as well against a panel of human and fish pathogenic bacteria. Following a bioactivity-guided isolation pipeline, a new analogue of the red-pigmented family of the antibiotics prodigiosins, decylprodigiosin (1), was identified and chemically characterized. Despite this family of natural products being well-known for a long time, we report a new analogue and the first evidence for prodigiosins being produced by a seaweed-associated actinomycete.

17.
Sci Total Environ ; 929: 172590, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38642746

RESUMO

Harmful cyanobacterial blooms have increased globally, releasing hazardous cyanotoxins that threaten the safety of water resources. Constructed wetlands (CWs) are a nature-based and low-cost solution to purify and remove cyanotoxins from water. However, bio-mechanistic understanding of the biotransformation processes expected to drive cyanotoxin removal in such systems is poor, and primarily focused on bacteria. Thus, the present study aimed at exploring the fungal contribution to microcystin-LR and cylindrospermopsin biodegradation in CWs. Based on CW mesocosms, two experimental approaches were taken: a) amplicon sequencing studies were conducted to investigate the involvement of the fungal community; and b) CW fungal isolates were tested for their microcystin-LR and cylindrospermopsin degradation capabilities. The data uncovered effects of seasonality (spring or summer), cyanotoxin exposure, vegetation (unplanted, Juncus effusus or Phragmites australis) and substratum (sand or gravel) on the fungal community structure. Additionally, the arbuscular mycorrhizal fungus Rhizophagus and the endophyte Myrmecridium showed positive correlations with cyanotoxin removal. Fungal isolates revealed microcystin-LR-removal potentials of approximately 25 % in in vitro biodegradation experiments, while the extracellular chemical fingerprint of the cultures suggested a potential intracellular metabolization. The results from this study may help us understand the fungal contribution to cyanotoxin removal, as well as their ecology in CWs.


Assuntos
Biodegradação Ambiental , Fungos , Microcistinas , Áreas Alagadas , Microcistinas/metabolismo , Fungos/metabolismo , Toxinas Bacterianas/metabolismo , Alcaloides/metabolismo , Toxinas de Cianobactérias , Toxinas Marinhas/metabolismo , Poluentes Químicos da Água/metabolismo , Eliminação de Resíduos Líquidos/métodos , Uracila/análogos & derivados , Uracila/metabolismo
18.
J Neurointerv Surg ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38479798

RESUMO

BACKGROUND: Fast and complete reperfusion in endovascular therapy (EVT) for ischemic stroke leads to superior clinical outcomes. The effect of changing the technical approach following initially unsuccessful passes remains undetermined. OBJECTIVE: To evaluate the association between early changes to the EVT approach and reperfusion. METHODS: Multicenter retrospective analysis of prospectively collected data for patients who underwent EVT for intracranial internal carotid artery, middle cerebral artery (M1/M2), or basilar artery occlusions. Changes in EVT technique after one or two failed passes with stent retriever (SR), contact aspiration (CA), or a combined technique (CT) were compared with repeating the previous strategy. The primary outcome was complete/near-complete reperfusion, defined as an expanded Thrombolysis in Cerebral Infarction (eTICI) of 2c-3, following the second and third passes. RESULTS: Among 2968 included patients, median age was 66 years and 52% were men. Changing from SR to CA on the second or third pass was not observed to influence the rates of eTICI 2c-3, whereas changing from SR to CT after two failed passes was associated with higher chances of eTICI 2c-3 (OR=5.3, 95% CI 1.9 to 14.6). Changing from CA to CT was associated with higher eTICI 2c-3 chances after one (OR=2.9, 95% CI 1.6 to 5.5) or two (OR=2.7, 95% CI 1.0 to 7.4) failed CA passes, while switching to SR was not significantly associated with reperfusion. Following one or two failed CT passes, switching to SR was not associated with different reperfusion rates, but changing to CA after two failed CT passes was associated with lower chances of eTICI 2c-3 (OR=0.3, 95% CI 0.1 to 0.9). Rates of functional independence were similar. CONCLUSIONS: Early changes in EVT strategies were associated with higher reperfusion and should be contemplated following failed attempts with stand-alone CA or SR.

19.
Phys Chem Chem Phys ; 26(9): 7865-7876, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38376442

RESUMO

Carotenoids are very effectively delivered by albumin to adipocytes. The uptake of carotenoids to the cells occurs in the form of self-aggregates that localize in the vicinity of the adipocyte membrane, as shown by high spatial resolution Raman spectroscopy. The binding of carotenoids to albumin and the mechanism of their transport were elucidated with the help of chiroptical spectroscopies, in tandem with molecular docking and molecular dynamics simulations. In particular, apart from the recognized high affinity pocket of albumin that binds a carotenoid monomer in domain I, we have identified a hydrophobic periphery area in domain IIIB that loosely bounds the self-aggregated carotenoid in aqueous media and enables its easy detachment in hydrophobic environments. This explains the effectiveness of albumins as nanocarriers of carotenoids to adipocytes in vitro.


Assuntos
Albuminas , Carotenoides , Carotenoides/química , Simulação de Acoplamento Molecular , Transporte Biológico , Adipócitos/metabolismo , Análise Espectral Raman/métodos
20.
J Hazard Mater ; 468: 133739, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38401210

RESUMO

Feast-famine (FF) regimes improved the removal of recalcitrant pharmaceuticals in moving bed biofilm reactors (MBBRs), but the optimal FF cycle remained unresolved. The effects of FF cycle time on the removal of bulk substrates (organic carbon and nitrogen) and trace pharmaceuticals by MBBR are systematically evaluated in this study. The feast to famine ratio was fixed to 1:2 to keep the same loading rate, but the time for the FF cycles varied from 18 h to 288 h. The MBBR adapted to the longest FF cycle time (288 h equaling 48 × HRT) resulted in significantly higher degradation rates (up to +183%) for 12 out of 28 pharmaceuticals than a continuously fed (non-FF) reactor. However, other FF cycle times (18, 36, 72 and 144 h) only showed a significant up-regulation for 2-3 pharmaceuticals compared to the non-FF reactor. Enantioselective degradation of metoprolol and propranolol occurred in the second phase of a two phase degradation, which was different for the longer FF cycle time. N-oxidation and N-demethylation pathways of tramadol and venlafaxine differed across the FF cycle time suggestin the FF cycle time varied the predominant transformation pathways of pharmaceuticals. The abundance of bacteria in the biofilms varied considerably between different FF cycle times, which possibly caused the biofilm to remove more recalcitrant bulk organic C and pharmaceuticals under long cycle times.


Assuntos
Eliminação de Resíduos Líquidos , Águas Residuárias , Biofilmes , Estereoisomerismo , Reatores Biológicos , Preparações Farmacêuticas
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