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1.
AME Case Rep ; 8: 111, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39380867

RESUMEN

Background: Multiple myeloma (MM) relapse in the central nervous system (CNS) confers an adverse prognosis, usually occurring in a short period after stem cell transplant and with a short overall survival. Isolated CNS relapse is so rare that there is no current standard treatment. Case Description: We present a 59-year-old male with an isolated CNS MM relapse, who had received autologous stem-cell transplant (ASCT) and thalidomide maintenance 11 years prior. He returned to our clinic with cauda equina syndrome and a nuclear magnetic resonance (NMR) identified a spinal lesion, a lumbar puncture was performed and plasma cells were identified in his cerebrospinal fluid (CSF). He was initially treated with intrathecal (IT) chemotherapy with methotrexate and steroid + radiotherapy and plasma cells disappeared after a few bi-weekly doses. Later on, treatment with pomalidomide/dexamethasone was given for 12 cycles with good clinical response with 80% recovery of his motor function. Conclusions: In this rare case of a very late CNS MM relapse, we demonstrate that IT chemotherapy complemented with a systemic pomalidomide-based treatment is safe and effective. This is particularly important in contexts where newer therapies such as bispecifics, chimeric antigen receptor-T (CAR-T) cells or even daratumumab or selinexor are not widely available. Further clinical experience in this particular scenario will be required to confirm this observation and define overall the best strategy for this rare group of patients.

2.
Heliyon ; 10(16): e36182, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39253194

RESUMEN

A new family of monothiooxalamides derived from 2-aminobenzimidazole was synthesized, and their structures were confirmed by 1H and 13C one-dimensional and 2D NMR experiments (COSY, HSQC, and HMBC). The antioxidant capacity was evaluated by free radical scavenging assays: 1,1-diphenyl-2-picrylhydrazyl (DPPH•), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS•+), ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), and the Fe(II) chelating ability. Our work group has previously reported the synthesis and antioxidant activity of monothiooxalamides derived from 2-aminopyridine (I). In this study, the in vitro hemolytic activity of compounds from the 2-aminopyridine (I) and 2-aminobenzimidazole (II) families was evaluated against human red blood cells (RBCs). The concentration at which monothiooxalamides showed no hemolytic activity was chosen to assess their ability to inhibit free radical-induced membrane damage in human RBCs, acute toxicity in brine shrimp, and in vivo toxicity against Drosophila melanogaster. Compounds with morpholine fragments (1g, 1h, 2g, and 2h) showed time- and concentration-dependent protective effects against radical-induced oxidative hemolysis. Moreover, they had the lowest acute toxicity in the brine shrimp lethality assay and a significant increase in chelating activity compared with the other molecules. In particular, monothiooxalamide 2g showed lower toxicity and can be considered for further biological screening and application trials.

3.
Behav Sci (Basel) ; 14(9)2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39335965

RESUMEN

INTRODUCTION: Emotional regulation, a process that involves detecting and evaluating physiological signals in response to stressful events, is a crucial aspect of preparing students for school and ensuring teachers' effectiveness, stress management, and job satisfaction. METHOD: This research, which adopted a quantitative approach, used a non-experimental comparative and cross-sectional design with a non-probabilistic sample by convenience. The study involved the participation of n = 1321 teachers (n = 125 preschool education; n = 645 primary education; n = 417 secondary education; n = 134 higher education). RESULTS: The results revealed significant differences in the total scores of emotional regulation difficulty between teachers at the higher education level and primary and secondary school teachers, with the latter group showing higher levels of difficulty. DISCUSSION: The findings suggest that the impact of emotional regulation difficulties affects professional performance, highlighting the importance of interventions aimed at improving teachers' self-efficacy, resilience, and emotion regulation to reduce emotional exhaustion. CONCLUSION: From a practical point of view, our findings underline the importance of integrating emotional regulation training into pre-service teacher education and continuous teacher professional development programs. This could improve relational dynamics between students and teachers, fostering an environment conducive to teaching and learning processes.

4.
Sci Total Environ ; 951: 175613, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39168330

RESUMEN

The ubiquity of microplastics (MP) across all ecosystems raises concerns about their potential harm to the environment and living organisms. Sediments are a MP sink, reflecting long-term accumulation and historical anthropogenic impacts. Three 210Pb-dated sediment cores were used to understand the temporal variations of MP abundances (particles kg-1) and fluxes (particles m-2 year-1) within the past century in Estero de Urías Lagoon, an urbanized coastal lagoon in the Mexican Pacific. MP particles, extracted from sediments by density separation (saturated NaCl solution) were counted using a stereomicroscope, under visible and ultraviolet light on Nile red (NR) stained filters. The polymer composition was determined in ∼10 % of the suspected MP particles using Fourier Transform Infrared spectrometry. Fibers (66 to 89 % of the total particles) predominated over fragments (11 to 34 %). Before 1950, no MP particles were detected. Polyethylene terephthalate (PET) was the prevalent synthetic polymer (up to 50 % of the particles), while semisynthetic cellulosic fibers were predominant, underscoring the broader scope of anthropogenic contamination. Suspected MP abundances (NR stained filters) were highest in the core collected at the innermost area, which was attributed to the lagoon's hydrodynamics, since current velocities decrease from the proximal to the distal area to the sea. From the regression between MP fluxes and time elapsed since sediments deposited, the cores showed consistent accelerated increases of MP burial since mid-20th century, most likely because of the increasing availability of plastic products and population growth, with the consequent increment in plastic waste and wastewater releases. Our findings emphasize the growing MP pollution challenges at EUL, which may directly impact subsistence fishing and shrimp aquaculture activities, threatening local livelihoods and food sources; and also highlight the need for improved waste management and pollution control strategies in rapidly industrializing regions, to protect both aquatic ecosystems and human populations dependent on fishing products.

5.
Front Microbiol ; 15: 1409729, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39135877

RESUMEN

Introduction: In recent decades, Caribbean coral reefs have lost many vital marine species due to diseases. The well-documented mass mortality event of the long-spined black sea urchin Diadema antillarum in the early 1980s stands out among these collapses. This die-off killed over 90% of D. antillarum changing the reefscape from coral to algal-dominated. Nearly 40 years later, D. antillarum populations have yet to recover. In early 2022, a new mortality event of D. antillarum was reported along the Caribbean, including Puerto Rico. Methods: This study identifies the gut microbiota changes associated with the D. antillarum during this mortality event. It contrasts them with the bacterial composition of gut samples from healthy individuals collected in 2019 by using 16S rRNA sequencing analyses. Results: Notably, the die-off group's core microbiome resembled bacteria commonly found in the human skin and gut, suggesting potential anthropogenic contamination and wastewater pollution as contributing factors to the 2022 dysbiosis. The animals collected in 2022, especially those with signs of disease, lacked keystone taxa normally found in Diadema including Photobacterium and Propionigenium. Discussion: The association between human microbes and disease stages in the long-spined urchin D. antillarum, especially in relation to anthropogenic contamination, highlights a complex interplay between environmental stressors and marine health. While these microbes might not be the direct cause of death in this species of sea urchins, their presence and proliferation can indicate underlying issues, such as immune depletion due to pollution, habitat destruction, or climate change, that ultimately compromise the health of these marine organisms.

6.
Plants (Basel) ; 13(13)2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38999578

RESUMEN

Disease severity and drought due to climate change present significant challenges to orchard productivity. This study examines the effects of spring inoculation with Pseudomonas syringae pv. syringae (Pss) on sweet cherry plants, cvs. Bing and Santina with varying defense responses, assessing plant growth, physiological variables (water potential, gas exchange, and plant hydraulic conductance), and the levels of abscisic acid (ABA) and salicylic acid (SA) under two summer irrigation levels. Pss inoculation elicited a more pronounced response in 'Santina' compared to 'Bing' at 14 days post-inoculation (dpi), and those plants inoculated with Pss exhibited a slower leaf growth and reduced transpiration compared to control plants during 60 dpi. During differential irrigations, leaf area was reduced 14% and 44% in Pss inoculated plants of 'Bing' and 'Santina' respectively, under well-watered (WW) conditions, without changes in plant water status or gas exchange. Conversely, water-deficit (WD) conditions led to gas exchange limitations and a 43% decrease in plant biomass compared to that under WW conditions, with no differences between inoculation treatments. ABA levels were lower under WW than under WD at 90 dpi, while SA levels were significantly higher in Pss-inoculated plants under WW conditions. These findings underscore the influence on plant growth during summer in sweet cherry cultivars that showed a differential response to Pss inoculations and how the relationship between ABA and SA changes in plant drought level responses.

7.
Children (Basel) ; 11(7)2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39062315

RESUMEN

BACKGROUND: A negative lifestyle has a reported relationship with psychological problems and deteriorated well-being. However, there is little information regarding the mediating role of cardiorespiratory fitness (CRF) in this relationship. OBJECTIVES: The objectives of the present study are twofold: first, to investigate the association between negative lifestyle, physical self-concept (PSC), and depression, and second, to assess the potential mediating role of CRF in this complex relationship. METHODS: This cross-sectional study included 612 schoolchildren aged between 9 and 14 years from the Araucanía region (southern Chile). CRF was measured using the Leger test, and lifestyle, depression, and PSC were measured using validated questionnaires. RESULTS: A negative lifestyle reported an inverse association with PSC (p < 0.001) and a positive association with depression levels (p < 0.001). The mediation analysis showed that CRF was positively related to PSC (p < 0.001) and inversely related to depression (p = 0.001); besides, the indirect effect CRF acted as a partial mediator in the association between a negative lifestyle and PSC (indirect effect = -1.15; SE = 0.01; 95% CI, -1.87, -0.55) and depression levels (indirect effect = 0.22; SE = 0.08; 95% CI, 0.08, 0.38). CONCLUSION: In conclusion, CRF in schoolchildren played a potential mediating role in the association between a negative lifestyle and depression and PSC.

8.
Behav Sci (Basel) ; 14(7)2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-39062377

RESUMEN

BACKGROUND: Little is known about the association between active commuting (i.e., walking or cycling to school) with lifestyle parameters and mental health in youths. The objective of the present study was to investigate the association between mental health problems and symptoms of depression, anxiety, and stress with lifestyle (i.e., food habits, screen time, physical activity, and sleep quality), active commuting, and gender. METHODS: A total of 511 children and adolescents (boys, n = 249; girls, n = 262) aged 10 to 17 years participated in the study. Lifestyle parameters and mental health were evaluated using the Depression Anxiety and Stress Scale (DASS-21). RESULTS: Girls reported higher levels of anxiety (p = 0.001), depression (p = 0.001), and stress (p = 0.001). Mental health problems showed a positive association with gender (girls, ß = 3.06, p < 0.001) and a negative association with food habits (ß = -0.65, p = 0.019). Anxiety was positively associated with gender (ß = 7.88, p < 0.001) and negatively associated with food habits (ß = -0.23, p = 0.019). Gender (girls) and food habits were also associated with symptoms of depression (ß = 2.29, p < 0.001 and ß = -0.27, p = 0.005, respectively). Finally, active commuting was inversely associated with stress (ß = -1.24, p = 0.008), and stress was positively linked to gender (ß = 2.53, p < 0.001). CONCLUSIONS: Active commuting, lifestyle parameters, and gender were associated with mental health in children and adolescents. Moreover, girls reported higher levels of anxiety, symptoms of depression, and stress.

9.
Sci Data ; 11(1): 585, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38839822

RESUMEN

Enhancing rapid phenotyping for key plant traits, such as biomass and nitrogen content, is critical for effectively monitoring crop growth and maximizing yield. Studies have explored the relationship between vegetation indices (VIs) and plant traits using drone imagery. However, there is a gap in the literature regarding data availability, accessible datasets. Based on this context, we conducted a systematic review to retrieve relevant data worldwide on the state of the art in drone-based plant trait assessment. The final dataset consists of 41 peer-reviewed papers with 11,189 observations for 11 major crop species distributed across 13 countries. It focuses on the association of plant traits with VIs at different growth/phenological stages. This dataset provides foundational knowledge on the key VIs to focus for phenotyping key plant traits. In addition, future updates to this dataset may include new open datasets. Our goal is to continually update this dataset, encourage collaboration and data inclusion, and thereby facilitate a more rapid advance of phenotyping for critical plant traits to increase yield gains over time.


Asunto(s)
Productos Agrícolas , Nitrógeno , Nitrógeno/análisis , Fenotipo , Plantas , Biomasa
10.
Plants (Basel) ; 13(10)2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38794433

RESUMEN

Bacterial canker is an important disease of sweet cherry plants mainly caused by Pseudomonas syringae pv. syringae (Pss). Water deficit profoundly impairs the yield of this crop. Nitric oxide (NO) is a molecule that plays an important role in the plant defense mechanisms. To evaluate the protection exerted by NO against Pss infection under normal or water-restricted conditions, sodium nitroprusside (SNP), a NO donor, was applied to sweet cherry plants cv. Lapins, before they were exposed to Pss infection under normal or water-restricted conditions throughout two seasons. Well-watered plants treated with exogenous NO presented a lower susceptibility to Pss. A lower susceptibility to Pss was also induced in plants by water stress and this effect was increased when water stress was accompanied by exogenous NO. The lower susceptibility to Pss induced either by exogenous NO or water stress was accompanied by a decrease in the internal bacterial population. In well-watered plants, exogenous NO increased the stomatal conductance and the net CO2 assimilation. In water-stressed plants, NO induced an increase in the leaf membranes stability and proline content, but not an increase in the CO2 assimilation or the stomatal conductance.

11.
Healthcare (Basel) ; 12(10)2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38786435

RESUMEN

BACKGROUND: A negative lifestyle is reported to be related to cognitive problems. However, there is little information about this in relation to university students. The objective of the present study was to investigate the association between executive functions (EFs) and lifestyle parameters (i.e., physical activity (PA), sleep duration, screen time (ST), and food habits) among Chilean university students. METHODS: This cross-sectional study included a total of 150 university students (94 females and 56 males, aged 21.28 ± 3.15 and 22.18 ± 2.90 years, respectively). Cognitive outcomes were measured using the CogniFit assessment battery. Lifestyle was measured through validated questionnaires. RESULTS: Across the total sample, attention exhibited a positive association with PA h/week (ß: 24.34 95% CI: 12.46 to 36.22, p = 0.001). Additionally, coordination was positively associated with PA h/week (ß: 15.06 95% CI: 0.62 to 29.50, p < 0.041). PA h/week was positively linked with reasoning (ß: 20.34 95% CI: 4.52 to 36.17, p = 0.012) and perception (ß: 13.81 95% CI: 4.14 to 23.49, p = 0.005). Moreover, PA h/week was significantly linked to memory (ß: 23.01 95% CI: 7.62 to 38.40, p = 0.004). In terms of the EFs, PA h/week showed a positive association with cognitive flexibility (ß: 45.60 95% CI: 23.22 to 67.69, p = 0.001). CONCLUSIONS: In conclusion, lifestyle (PA h/week) was positively associated with EFs. Therefore, an increase in PA levels among these students should be a target for community- and university-based interventions in order to promote cognitive development such as attention, coordination, reasoning, perception, memory, and cognitive flexibility.

13.
Org Biomol Chem ; 22(16): 3328-3339, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38584463

RESUMEN

Fullerene C60 and its malonate derivatives, produced via the Bingel-Hirsch reaction, have displayed promising properties against various diseases. These molecules have great therapeutic potential, but their broad use has been limited due to poor aqueous solubility and toxicity caused by accumulation. In this study, we synthesized new malonates and malonamides attached to first- and second-generation polyester dendrons using click chemistry (CuAAC). These dendrons were then linked at C60 through the Bingel-Hirsch reaction, resulting in an amphiphilic system that retains the hydrophobic nature of C60. The dendronized malonate derivatives showed good reaction yields for the Bingel-Hirsch mono-adducts and were easier to work with than the corresponding malonamides. However, the malonamide derivatives, which were obtained through a multistep reaction sequence, showed moderate yields in the Bingel-Hirsch reaction. Surprisingly, removing acetonide protecting groups from dendritic architectures was more challenging than anticipated, likely due to product decomposition. Only the corresponding free malonate derivatives 25 and 26 were obtained, but in a low yield due to decomposition under the reaction conditions. Meanwhile, it was not possible to obtain the corresponding malonamide derivatives 27 and 28. Currently, efforts are being made to improve the production of the desired molecules and to design new synthesis routes that allow direct access to the desired poly-hydroxylated derivatives. These derivatives will be evaluated as multitarget ligands against Alzheimer's disease, through their use as inhibitors of amyloid ß-peptide aggregation, acetylcholinesterase modulators, and antioxidants.

14.
Environ Monit Assess ; 196(5): 422, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38570386

RESUMEN

The exposure to arsenic and mercury in various insect trophic guilds from two mercury mining sites in Mexico was assessed. The two study sites were La Laja (LL) and La Soledad (LS) mines. Additionally, a reference site (LSR) was evaluated for LS. The terrestrial ecosystem was studied at LL, whereas both the terrestrial ecosystem and a stream called El Cedral (EC) were assessed at LS. The study sites are situated in the Biosphere Reserve Sierra Gorda (BRSG). Mercury vapor concentrations were measured with a portable analyzer, and concentrations of arsenic and mercury in environmental and biological samples were determined through atomic absorption spectrophotometry. Both pollutants were detected in all terrestrial ecosystem components (soil, air, leaves, flowers, and insects) from the two mines. The insect trophic guilds exposed included pollinivores, rhizophages, predators, coprophages, and necrophages. In LS, insects accumulated arsenic at levels 29 to 80 times higher than those found in specimens from LSR, and 10 to 46 times higher than those from LL. Similarly, mercury exposure in LS was 13 to 62 times higher than LSR, and 15 to 54 times higher than in LL. The analysis of insect exposure routes indicated potential exposure through air, soil, leaves, flowers, animal prey, carrion, and excrement. Water and sediment from EC exhibited high levels of arsenic and mercury compared to reference values, and predatory aquatic insects were exposed to both pollutants. In conclusion, insects from mercury mining sites in the BRSG are at risk.


Asunto(s)
Arsénico , Contaminantes Ambientales , Mercurio , Animales , Mercurio/análisis , Arsénico/análisis , Ecosistema , Monitoreo del Ambiente , México , Insectos , Contaminantes Ambientales/análisis , Minería , Suelo
16.
Sci Total Environ ; 920: 170609, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38316296

RESUMEN

Spatial and temporal variations of mercury (Hg) concentrations, enrichment, and potential ecological risks were studied in a suite of lead-210 (210Pb) dated sediment cores from 13 Wider Caribbean Region coastal environments. Broad variability of Hg concentrations (19-18761 ng g-1) was observed, encompassing even background levels (38-100 ng g-1). Most Hg concentration profiles exhibited a characteristic upward trend, reaching their peak values in the past two decades. Most of the sediment sections, showing from moderately to very severe Hg enrichment, were found in cores from Havana Bay and Sagua River Estuary (Cuba), Port-au-Prince Bay (Haiti), and Cartagena Bay (Colombia). These were also the most seriously contaminated sites, which can be considered regional Hg 'hotspots'. Both Havana Bay and Port-au-Prince Bay reportedly receive waste from large cities with populations exceeding 2 million inhabitants, and watersheds affected by high erosion rates. The records from the Sagua River Estuary and Cartagena Bay reflected historical Hg contamination associated with chloralkali plants, and these sites are of very high ecological risk. These results constitute a major contribution to the scarce regional data on contaminants in the Wider Caribbean Region and provide reference information to support the evaluation of the effectiveness of the Minamata Convention.

17.
Sci Total Environ ; 916: 170340, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38278249

RESUMEN

Although considered one of the most pristine ecosystems, Antarctica has been largely influenced by human activities during the last 50 years, affecting its unique biodiversity. One of the major global threats to health is the emergence of antibiotic-resistant bacteria that may be actively transferred to wildlife. We cultured and tested for antibiotic resistance in 137 cloacal and fresh fecal samples of several avian and marine mammal species from the Antarctic Peninsula, the most impacted area in Antarctica. Alarmingly, 80 % of the isolates showed antibiotic resistance, either phenotypically or genotypically. Most of the resistant bacteria, such as Enterobacteriaceae and Enterococcus species, are part of local gastrointestinal microbiota. Penguins and pinnipeds harbored a great diversity of antibiotic resistance and must be eligible as sentinels for future studies. These results show that antibiotic resistance has rapidly transferred to bacteria in Antarctic wildlife, which is a global matter of concern.


Asunto(s)
Caniformia , Spheniscidae , Animales , Humanos , Animales Salvajes , Ecosistema , Regiones Antárticas , Farmacorresistencia Microbiana , Bacterias
18.
PeerJ ; 12: e16700, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38188168

RESUMEN

Background: Seagrass meadows, known for providing essential ecosystem services like supporting fishing, coastline protection from erosion, and acting as carbon sinks to mitigate climate change effects, are facing severe degradation. The current deteriorating state can be attributed to the combination of anthropogenic activities, biological factors (i.e., invasive species), and natural forces (i.e., hurricanes). Indeed, the global seagrass cover is diminishing at an alarming mean rate of 7% annually, jeopardizing the health of these vital ecosystems. However, in the Island Municipality of Culebra, Puerto Rico, losses are occurring at a faster pace. For instance, hurricanes have caused over 10% of cover seagrass losses, and the natural recovery of seagrasses across Culebra's coast has been slow due to the low growth rates of native seagrasses (Thalassia testudinum and Syringodium filiforme) and the invasion of the invasive species Halophila stipulacea. Restoration programs are, thus, necessary to revitalize the native seagrass communities and associated fauna while limiting the spread of the invasive species. Methods: Here, we present the results of a seagrass meadow restoration project carried out in Punta Melones (PTM), Culebra, Puerto Rico, in response to the impact of Hurricanes Irma and María during 2017. The restoration technique used was planting propagation units (PUs), each with an area of 900 cm2 of native seagrasses Thalassia testudinum and Syringodium filiforme, planted at a depth between 3.5 and 4.5 m. A total of 688 PUs were planted between August 2021 and August 2023, and a sub-sample of 88 PUs was monitored between August 2021 and April 2023. Results: PUs showed over 95% of the seagrass survived, with Hurricane Fiona causing most of the mortalities potentially due to PUs burial by sediment movement and uplifting by wave energy. The surface area of the planting units increased by approximately 200% (i.e., 2,459 cm2), while seagrass shoot density increased by 168% (i.e., 126 shoots by PU). Additionally, flowering and fruiting were observed in multiple planting units, indicating 1) that the action taken did not adversely affect the PUs units and 2) that the project was successful in revitalizing seagrass populations. The seagrass restoration project achieved remarkable success, primarily attributed to the substantial volume of each PUs. Likely this high volume played a crucial role in facilitating the connection among roots, shoots, and microfauna while providing a higher number of undamaged and active rhizome meristems and short shoots. These factors collectively contributed to the enhanced growth and survivorship of the PUs, ultimately leading to the favorable outcome observed in the seagrass restoration project.


Asunto(s)
Alismatales , Brugmansia , Hydrocharitaceae , Ecosistema , Efectos Antropogénicos , Supuración
19.
Toxins (Basel) ; 16(1)2024 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-38276536

RESUMEN

Ciguatera, a global issue, lacks adequate capacity for ciguatoxin analysis in most affected countries. The Caribbean region, known for its endemic ciguatera and being home to a majority of the global small island developing states, particularly needs established methods for ciguatoxin detection in seafood and the environment. The radioligand receptor binding assay (r-RBA) is among the in vitro bioassays currently used for ciguatoxin analysis; however, similarly to the other chemical-based or bioassays that have been developed, it faces challenges due to limited standards and interlaboratory comparisons. This work presents a single laboratory validation of an r-RBA developed in a Cuban laboratory while characterizing the performance of the liquid scintillation counter instrument as a key external parameter. The results obtained show the assay is precise, accurate and robust, confirming its potential as a routine screening method for the detection and quantification of ciguatoxins. The new method will aid in identifying high-risk ciguatoxic fish in Cuba and the Caribbean region, supporting monitoring and scientific management of ciguatera and the development of early warning systems to enhance food safety and food security, and promote fair trade fisheries.


Asunto(s)
Intoxicación por Ciguatera , Ciguatoxinas , Animales , Ciguatoxinas/análisis , Intoxicación por Ciguatera/diagnóstico , Peces , Unión Proteica , Bioensayo
20.
J Med Chem ; 66(23): 16222-16234, 2023 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-38051546

RESUMEN

Duclauxin (1) from Talaromyces sp. IQ-313 was reported as a putative allosteric modulator of human recombinant protein tyrosine phosphatase 1B (400 amino acids) (hPTP1B1-400), a validated target for the treatment of type II diabetes. Based on these findings, a one-strain-many-compound (OSMAC) experiment on the IQ-313 strain generated derivatives 5a, 6, and 7. Moreover, a one-/two-step semisynthetic approach guided by docking toward hPTP1B1-400 produced 38 analogs, a series (A) incorporating a lactam functionalization at C-1 (8a-15a, 36a, and 37a) and a series (B) containing a lactam at C-1 and an extra unsaturation between C-7 and C-8 (5b, 11b-37b). In vitro evaluation and structure-activity relationship (SAR) analysis revealed that analogs from the B series are up to 10-fold more active than 1 and derivatives from the A series. Furthermore, duclauxin (1) and 36b were assessed for their potential acute toxicity, estimating their LD50 to be higher than 300 mg/kg. Moreover, 36b significantly reduced glycemia in an insulin tolerance test in mice, suggesting that its mechanism of action is through the PTP1B inhibition.


Asunto(s)
Diabetes Mellitus Tipo 2 , Ratones , Humanos , Animales , Diabetes Mellitus Tipo 2/metabolismo , Relación Estructura-Actividad , Lactamas , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Simulación del Acoplamiento Molecular , Proteína Tirosina Fosfatasa no Receptora Tipo 1/metabolismo
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