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1.
Curr Issues Mol Biol ; 46(8): 8726-8740, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39194732

RESUMEN

This study aimed to evaluate the efficacy of the ethanolic extract of Anadenanthera colubrina in modulating the immune response in the Experimental Autoimmune Encephalomyelitis (EAE) model. The ethanolic extract of the dried bark was analyzed by ESI (+) Orbitrap-MS to obtain a metabolite profile, demonstrating a wide variety of polyphenols, such as flavonoids and phenolic acids. Various parameters were evaluated, such as clinical signs, cytokines, cellular profile, and histopathology in the central nervous system (CNS). The ethanolic extract of A. colubrina demonstrated significant positive effects attenuating the clinical signs and pathological processes associated with EAE. The beneficial effects of the extract treatment were evidenced by reduced levels of pro-inflammatory cytokines, such as IL1ß, IL-6, IL-12, TNF, IFN-γ, and a notable decrease in several cell profiles, including CD8+, CD4+, CD4+IFN-γ, CD4+IL-17+, CD11c+MHC-II+, CD11+CD80+, and CD11+CD86+ in the CNS. In addition, histological analysis revealed fewer inflammatory infiltrates and demyelination sites in the spinal cord of mice treated with the extract compared to the control model group. These results showed, for the first time, that the ethanolic extract of A. colubrina exerts a modulatory effect on inflammatory processes, improving clinical signs in EAE, in the acute phase of the disease, which could be further explored as a possible therapeutic alternative.

2.
Curr Top Med Chem ; 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39136508

RESUMEN

BACKGROUND: This study investigates the potential of eleven 1H-1,2,3-triazol-1,4-naphthoquinone conjugates as virulence factor inhibitors (like Pyocyanin) and their affinity for PhzM, a crucial enzyme for Pyocyanin biosynthesis in Pseudomonas aeruginosa infections. METHODS: A straightforward synthetic pathway enabled the production of these compounds, which were characterized and structurally confirmed through spectroscopic analyses. Evaluation of their impact on PhzM thermal stability identified promising candidates for PhzM binders. RESULTS: Concentration-response behavior elucidated their binding affinity, revealing them as the first reported micromolar affinity ligands for PhzM. Structure-activity relationship analysis emphasized the role of specific molecular moieties in binding affinity modulation, paving the way for future advanced inhibitors' development. CONCLUSION: These findings highlight the potential of naphthoquinone-triazole derivatives as leads for novel therapeutics against P. aeruginosa infections.

4.
Biodivers Data J ; 12: e125727, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38948134

RESUMEN

Background: The investigation of Agaricales diversity in the Antarctica is limited, with only seven genera reported for the region. Galerina stands out as the genus with the highest species diversity, including 12 species in Antarctica. This research reports the presence of G.marginata in the region, providing the first complete morphological description for the specimen developing in Antarctica. Sampling was conducted during the Austral summer of 2022/2023 as part of the XLI Brazilian Antarctic Operation in Point Smellie, Byers Peninsula, Livingston Island, South Shetland Archipelago, Antarctica. Phylogenetic relationships reconstructed by Maximum Likelihood demonstrate that G.marginata forms a monophyletic clade with over 60% bootstrap support in most branches. The isolate in this study was found to be internal to the main cluster. Evolutionary reconstructions using the Maximum Likelihood method indicate that the branches correspond to the Antarctic isolate being an internal clade within the marginata group. Recording fungal populations in polar regions offers information about their adaptation and survival in inhospitable environments. Understanding the species' distribution in Antarctica encourages future investigations into its ecology and interactions with other organisms. Here, data are presented to establish an initial foundation for monitoring the G.marginata population in Antarctica and assessing the potential impacts of climate change on its development and survival in the forthcoming years. New information: We report the third occurrence of Galerinamarginata (Batsch) Kühner in Antarctica and provide, for the first time, a comprehensive morphological description of an individual of the species for the Antarctic continent, accompanied by phylogenetic analyses and comprehensive discussions regarding its diversity and global distribution.

5.
Anim Reprod ; 21(2): e20230095, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39021494

RESUMEN

Tadalafil, a potent phosphodiesterase inhibitor 5 (PDE-5), is commonly used for the management of erectile dysfunction. However, its therapeutic potential extends beyond this indication. This study aimed to investigate the impact of tadalafil on the recovery of testicular parenchyma in male Wistar rats exposed to testicular thermal stress. Fifty-four Wistar rats were subjected to testicular thermal stress and randomly assigned to receive either tadalafil treatment (TAD) or no treatment (control). TAD was administered intraperitoneally at a dose of either 0.9 mg/kg or 1.8 mg/kg. Biometric parameters, histopathological assessment of the testis, serum testosterone levels, oxidative stress, and interleukin levels were evaluated on days 7, 15, and 30 after thermal shock. The animals were euthanized at the end of each experimental period, and samples were collected. TAD treatment maintained testicular weight and reduced the testicular degenerative process up to day 7 post-injury. However, despite TAD therapy, serum testosterone levels were decreased in the treated groups at days 7 and 15 post-thermal stress. TAD also decreased TNF-α and NO levels at different doses but had no effect on IL-6. The treatment with TAD after heat shock demonstrated anti-inflammatory and antioxidant properties but did not prevent the aggravation of testicular lesions in subsequent periods, even with the systematic reduction in TNF-α and NO levels. Therefore, this selective PDE-5 inhibitor, at the dosages used, did not have a positive impact on testosterone levels during the post-thermal stress period, which could compromise the resumption of the spermatogenic process.

6.
Acta Med Port ; 2024 Jul 15.
Artículo en Portugués | MEDLINE | ID: mdl-39008637

RESUMEN

Cytomegalovirus (CMV) is a type of double-stranded deoxyribonucleic acid virus belonging to the herpesviridae family. Following a primary infection, the virus becomes latent in various types of white blood cells. Cytomegalovirus infection can remain latent or become active, especially in immunocompromised individuals, such as those undergoing hematopoietic stem cell transplantation (HSCT), where CMV reactivation can occur. In this context, CMV infection is common and associated with high rates of morbidity and mortality. Pneumonia is one of the most serious complications, with mortality rates exceeding 50%. Additionally, even in the absence of organ-specific disease, CMV infection is related to increased mortality unrelated to hematologic neoplasm recurrence. Given the frequency and severity of this infection in HSCT patients, it is crucial to implement effective strategies for monitoring, prevention, and treatment. This guideline was developed to identify patient groups that benefit from a systematic approach to CMV infection and to define the most appropriate strategy for each group. Monitoring CMV viral load in peripheral blood is crucial, especially in patients at moderate to high risk of active infection. Primary prophylaxis with letermovir (an antiviral drug) is recommended to reduce the incidence of active infection, especially in high-risk patients. Secondary prophylaxis with valganciclovir (antiviral drug) is recommended after an episode of active infection, while preemptive and disease treatment is based on monitoring viral load and clinical response. The aim of this guideline is to improve the approach to CMV infection in HSCT patients, ensuring an effective and safe preventive and therapeutic approach.


O vírus citomegálico (CMV) é um tipo de vírus de ácido desoxirribonucleico de dupla cadeia que pertence à família herpesviridae. Após uma infeção primária, o vírus torna-se latente em vários tipos de glóbulos brancos. A infeção por CMV pode permanecer latente ou tornar-se ativa, especialmente em indivíduos imunodeprimidos, como aqueles submetidos a transplantes de células progenitoras hematopoiéticas (TPH), onde a reativação do CMV pode ocorrer. Neste contexto, a infeção por CMV é comum e associada a elevadas taxas de morbilidade e mortalidade. A pneumonite é uma das complicações mais graves, com taxas de mortalidade superiores a 50%. Além disso, mesmo na ausência de doença específica do órgão, a infeção por CMV está relacionada com um aumento da mortalidade não relacionada com a recidiva da neoplasia hematológica. Dada a frequência e gravidade desta infeção em doentes submetidos a TPH, é crucial implementar estratégias eficazes de monitorização, prevenção e tratamento. Este protocolo foi desenvolvido para identificar os grupos de doentes que se beneficiam de uma abordagem sistematizada para a infeção por CMV e definir a estratégia mais adequada para cada grupo. A monitorização da carga viral de CMV no sangue periférico é fundamental, especialmente em doentes com risco moderado a elevado de infeção ativa. A profilaxia primária com letermovir (fármaco antiviral) é recomendada para reduzir a incidência de infeção ativa, especialmente em doentes com alto risco. A profilaxia secundária com valganciclovir (fármaco antiviral) é recomendada após um episódio de infeção ativa, enquanto o tratamento de antecipação e de doença é baseado na monitorização da carga viral e na resposta clínica. Este protocolo visa melhorar a abordagem da infeção por CMV em doentes submetidos a TPH, garantindo uma abordagem preventiva e terapêutica eficaz e segura.

7.
Am J Hematol ; 99(9): 1768-1777, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38884175

RESUMEN

Crovalimab is a novel C5 complement inhibitor that enables rapid and sustained C5 inhibition with subcutaneous, low-volume self-administration every 4 weeks. COMMODORE 2 (NCT04434092) is a global, randomized, open-label, multicenter, phase 3 trial evaluating the non-inferiority of crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria not previously treated with C5 inhibition. C5 inhibitor-naive patients with lactate dehydrogenase (LDH) ≥2 × upper limit of normal (ULN) were randomized 2:1 to crovalimab or eculizumab. Co-primary efficacy endpoints were proportion of patients with hemolysis control (centrally assessed LDH ≤1.5 × ULN) and proportion with transfusion avoidance. Secondary efficacy endpoints were proportions of patients with breakthrough hemolysis, stabilized hemoglobin, and change in FACIT-Fatigue score. The primary treatment period was 24 weeks. Two hundred and four patients were randomized (135 crovalimab; 69 eculizumab). Crovalimab was non-inferior to eculizumab in the co-primary endpoints of hemolysis control (79.3% vs. 79.0%; odds ratio, 1.0 [95% CI, 0.6, 1.8]) and transfusion avoidance (65.7% vs. 68.1%; weighted difference, -2.8 [-15.7, 11.1]), and in the secondary efficacy endpoints of breakthrough hemolysis (10.4% vs. 14.5%; weighted difference, -3.9 [-14.8, 5.3]) and hemoglobin stabilization (63.4% vs. 60.9%; weighted difference, 2.2 [-11.4, 16.3]). A clinically meaningful improvement in FACIT-Fatigue score occurred in both arms. Complete terminal complement activity inhibition was generally maintained with crovalimab. The safety profiles of crovalimab and eculizumab were similar with no meningococcal infections. Most patients who switched from eculizumab to crovalimab after the primary treatment period preferred crovalimab. These data demonstrate the positive benefit-risk profile of crovalimab.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Inactivadores del Complemento , Hemoglobinuria Paroxística , Humanos , Hemoglobinuria Paroxística/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Adulto , Inactivadores del Complemento/uso terapéutico , Inactivadores del Complemento/efectos adversos , Hemólisis/efectos de los fármacos , Complemento C5/antagonistas & inhibidores , Anciano
8.
Appetite ; 201: 107581, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38945368

RESUMEN

The Mediterranean Diet has been recognized as one of the healthiest and most sustainable dietary patterns and is flavor rich due to the use of different seasonings, such as aromatic plants, in dish confection. Based on the hypotheses that: 1) gustatory function will affect food choices; 2) seasoning flavors may be differently accepted according to individuals' gustatory functions; the aim of the present study was to assess the association between taste sensitivity and/or preference with Mediterranean Diet adherence and seasoning consumption. A total of 383 adults (18-59 years old; 198 female, 185 male) from North Alentejo region of Portugal were enrolled in this study, with 291 (145 female and 146 male) also evaluated for gustatory function. Recognition thresholds were obtained for four tastes (sweet, sour, salty, and bitter) and astringency, as well as preference level for the highest concentration of each stimulus tested. A validated Food Frequency Questionnaire was filled out, and MD adherence was extrapolated from the answers of the Food Frequency Questionnaire according to the Mediterranean Diet Adherence Screener (MEDAS) score. In total, 20.8% of the individuals presented low, 58.2% medium, and 21.0% high adherence. Adherence was higher in women than men and in older individuals than younger adults. Adherence to the Mediterranean Diet was positively correlated with aromatic plants consumption but not spices. Seasonings were associated with gustatory function, and the cluster with higher consumption presented higher preferences for bitter and salty tastes. Total sodium intake was also higher in this cluster, suggesting that these individuals prefer stronger oral sensations. In conclusion, this study shows that MD adherence is not high, even in regions with rural characteristics. The observed association of MD and seasoning intake with gustatory function do underline the usefulness of this information in strategies aimed at promoting healthy and sustainable eating patterns.


Asunto(s)
Dieta Mediterránea , Preferencias Alimentarias , Gusto , Humanos , Femenino , Masculino , Adulto , Portugal , Dieta Mediterránea/estadística & datos numéricos , Persona de Mediana Edad , Adulto Joven , Adolescente , Cooperación del Paciente/estadística & datos numéricos , Encuestas y Cuestionarios , Conducta Alimentaria/psicología , Umbral Gustativo/fisiología
9.
Rev Soc Bras Med Trop ; 57: e007062024, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38896655

RESUMEN

BACKGROUND: Pressatia choti is a common sand fly found in the Atlantic Forest of Brazil, which is suspected to be involved in the transmission of Leishmania braziliensis. Herein, we aimed to establish a Pr. choti laboratory colony. METHODS: Wild-caught female sand flies were blood fed on hamsters and maintained under controlled conditions (temperature: 26 °C; relative humidity: 70%). RESULTS: Of the 301 collected female sandflies, 288 were identified as Pr. choti. The life cycle duration ranged from 31 to 56 days. CONCLUSIONS: We successfully established a Pr. choti colony, whose biological parameters were similar to those of other neotropical sand flies.


Asunto(s)
Insectos Vectores , Leishmania braziliensis , Psychodidae , Animales , Psychodidae/clasificación , Psychodidae/parasitología , Femenino , Insectos Vectores/clasificación , Insectos Vectores/parasitología , Brasil , Cricetinae
10.
Curr Med Chem ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38877863

RESUMEN

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.

11.
J Mol Model ; 30(6): 183, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38782773

RESUMEN

CONTEXT: The activation of C-H bonds is a fundamental process in synthetic organic chemistry, which enables their replacement by highly reactive functional groups. Coordination compounds serve as effective catalysts for this purpose, as they facilitate chemical transformations by interacting with C-H bonds. A comprehensive understanding of the mechanism of activation of this type of bond lays the foundation for the development of efficient protocols for cross-coupling reactions. We explored the activation of C(sp2)-H bonds in 1-Phenyl-4-vinyl-1H-1,2,3-triazole derivatives with CH3, OCH3, and NO2 substituents in the para position of the phenyl ring, using palladium acetate as catalyst. The studied reaction is the first step for subsequent conjugation of the triazoles with naphthoquinones in a Heck-type reaction to create a C-C bond. The basic nitrogen atoms of the 1,2,3-triazole coordinate preferentially with the cationic palladium center to form an activated species. A concerted proton transfer from the terminal vinyl carbon to one of the acetate ligands with low activation energy is the main step for the C(sp2)-H activation. This study offers significant mechanistic insights for enhancing the effectiveness of C(sp2)-H activation protocols in organic synthesis. METHODS: All calculations were performed using the Gaussian 09 software package and density functional theory (DFT). The structures of all reaction path components were fully optimized using the CAM-B3LYP functional with the Def2-SVP basis set. The optimized geometries were analyzed by computing the second-order Hessian matrix to confirm that the corresponding minimum or transition state was located. To account for solvent effects, the Polarizable Continuum Model of the Integral Equation Formalism (IEFPCM) with water as the solvent was used.

12.
Curr Sports Med Rep ; 23(5): 199-206, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38709946

RESUMEN

ABSTRACT: Breath-hold divers, also known as freedivers, are at risk of specific injuries that are unique from those of surface swimmers and compressed air divers. Using peer-reviewed scientific research and expert opinion, we created a guide for medical providers managing breath-hold diving injuries in the field. Hypoxia induced by prolonged apnea and increased oxygen uptake can result in an impaired mental state that can manifest as involuntary movements or full loss of consciousness. Negative pressure barotrauma secondary to airspace collapse can lead to edema and/or hemorrhage. Positive pressure barotrauma secondary to overexpansion of airspaces can result in gas embolism or air entry into tissues and organs. Inert gas loading into tissues from prolonged deep dives or repetitive shallow dives with short surface intervals can lead to decompression sickness. Inert gas narcosis at depth is commonly described as an altered state similar to that experienced by compressed air divers. Asymptomatic cardiac arrhythmias are common during apnea, normally reversing shortly after normal ventilation resumes. The methods of glossopharyngeal breathing (insufflation and exsufflation) can add to the risk of pulmonary overinflation barotrauma or loss of consciousness from decreased cardiac preload. This guide also includes information for medical providers who are tasked with providing medical support at an organized breath-hold diving event with a list of suggested equipment to facilitate diagnosis and treatment outside of the hospital setting.


Asunto(s)
Barotrauma , Contencion de la Respiración , Enfermedad de Descompresión , Buceo , Humanos , Buceo/lesiones , Buceo/efectos adversos , Barotrauma/etiología , Barotrauma/diagnóstico , Enfermedad de Descompresión/terapia , Enfermedad de Descompresión/etiología , Enfermedad de Descompresión/diagnóstico , Hipoxia/etiología , Narcosis por Gas Inerte/etiología , Narcosis por Gas Inerte/diagnóstico
13.
Environ Monit Assess ; 196(6): 540, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38733434

RESUMEN

X-ray fluorescence is a fast, cost-effective, and eco-friendly method for elemental analyses. Portable X-ray fluorescence spectrometers (pXRF) have proven instrumental in detecting metals across diverse matrices, including plants. However, sample preparation and measurement procedures need to be standardized for each instrument. This study examined sample preparation methods and predictive capabilities for nickel (Ni) concentrations in various plants using pXRF, employing empirical calibration based on inductively coupled plasma optical emission spectroscopy (ICP-OES) Ni data. The evaluation involved 300 plant samples of 14 species with variable of Ni accumulation. Various dwell times (30, 60, 90, 120, 300 s) and sample masses (0.5, 1.0, 1.5, 2.0 g) were tested. Calibration models were developed through empirical and correction factor approaches. The results showed that the use of 1.0 g of sample (0.14 g cm-2) and a dwell time of 60 s for the study conditions were appropriate for detection by pXRF. Ni concentrations determined by ICP-OES were highly correlated (R2 = 0.94) with those measured by the pXRF instrument. Therefore, pXRF can provide reliable detection of Ni in plant samples, avoiding the digestion of samples and reducing the decision-making time in environmental management.


Asunto(s)
Monitoreo del Ambiente , Níquel , Plantas , Espectrometría por Rayos X , Níquel/análisis , Monitoreo del Ambiente/métodos , Monitoreo del Ambiente/instrumentación , Espectrometría por Rayos X/métodos , Plantas/química , Contaminantes del Suelo/análisis
14.
Chemosphere ; 361: 142355, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38768787

RESUMEN

As global effects of water scarcity raise concerns and environmental regulations evolve, contemporary wastewater treatment plants (WWTPs) face the challenge of effectively removing a diverse range of contaminants of emerging concern (CECs) from municipal effluents. This study focuses on the assessment of advanced oxidation processes (AOPs), specifically UV-C/H2O2 and UV-C/Chlorine, for the removal of 14 target CECs in municipal secondary effluent (MSE, spiked with 10 µg L-1 of each CEC) or in the subsequent MSE nanofiltration retentate (NFR, no spiking). Phototreatments were carried out in continuous mode operation, with a hydraulic retention time of 3.4 min, using a tube-in-tube membrane photoreactor. For both wastewater matrices, UV-C photolysis (3.3 kJ L-1) exhibited high efficacy in removing CECs susceptible to photolysis, although lower treatment performance was observed for NFR. In MSE, adding 10 mg L-1 of H2O2 or Cl2 enhanced treatment efficiency, with UV-C/H2O2 outperforming UV-C/Chlorine. Both UV-C/AOPs eliminated the chronic toxicity of MSE toward Chlorella vulgaris. In the NFR, not only was the degradation of target CECs diminished, but chronic toxicity to C. vulgaris persisted after both UV-C/AOPs, with UV-C/Chlorine increasing toxicity due to potential toxic by-products. Nanofiltration permeate (NFP) exhibited low CECs and microbial content. A single chlorine addition effectively controlled Escherichia coli regrowth for 3 days, proving NFP potential for safe reuse in crop irrigation (<1 CFU/100 mL for E. coli; <1 mg L-1 for free chlorine). These findings provide valuable insights into the applications and limitations of UV-C/H2O2 and UV-C/Chlorine for distinct wastewater treatment scenarios.


Asunto(s)
Cloro , Filtración , Peróxido de Hidrógeno , Fotólisis , Rayos Ultravioleta , Eliminación de Residuos Líquidos , Aguas Residuales , Contaminantes Químicos del Agua , Peróxido de Hidrógeno/química , Aguas Residuales/química , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/análisis , Eliminación de Residuos Líquidos/métodos , Cloro/química , Filtración/métodos , Purificación del Agua/métodos , Chlorella vulgaris/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Oxidación-Reducción
15.
Curr Res Microb Sci ; 6: 100242, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38799088

RESUMEN

Mucormycosis is a severe fungal infection that demands immediate and decisive intervention upon suspicion. The causative agents of mucormycosis exhibit inherent resistance to echinocandins and voriconazole, and their in vitro susceptibility to terbinafine is highly variable and species-specific. Considering these factors and the limitations of currently available antifungal therapies, the identification of novel antifungals with potent activity against mucormycosis is of paramount importance. This study aims to identify compounds from the MMV Pathogen Box® presenting antifungal activity against selected mucormycosis agents and to evaluate their potential synergistic effects when combined with antifungal drugs. A screening of the Pathogen Box® compounds was conducted, isolated or in combination with sub-inhibitory concentrations of amphotericin B, isavuconazole or posaconazole, against a Rhizopus oryzae strain. Hits from the screenings were further evaluated against eight Mucoralean strains for minimal inhibitory and fungicidal concentration determinations and to confirm synergistic interactions using the checkerboard method. Ultrastructural studies were performed using scanning electron microscopy. MMV675968 exhibited fungicidal activity against a R. oryzae strain. All but one Rhizopus spp. strains presented MIC ≤ 1 µg/mL, with a geometric mean of 0.78 µg/mL observed across all isolates for this compound, which did not change significantly the cellular structure of this fungus. The combination screening with antifungal drugs revealed six additional compounds potentially active against the R. oryzae strain, two of them demonstrated proven synergism through the checkerboard assay. This first study with the MMV Pathogen Box® and Zigomycetes highlights promising new treatment options for mucormycosis in the future.

16.
ACS Omega ; 9(20): 21948-21963, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38799368

RESUMEN

Due to the growth in the number of patients and the complexity involved in anticancer therapies, new therapeutic approaches are urgent and necessary. In this context, compounds containing the selenium atom can be employed in developing new medicines due to their potential therapeutic efficacy and unique modes of action. Furthermore, tellurium, a previously unknown element, has emerged as a promising possibility in chalcogen-containing compounds. In this study, 13 target compounds (9a-i, 10a-c, and 11) were effectively synthesized as potential anticancer agents, employing a CuI-catalyzed Csp-chalcogen bond formation procedure. The developed methodology yielded excellent results, ranging from 30 to 85%, and the compounds were carefully characterized. Eight of these compounds showed promise as potential therapeutic drugs due to their high yields and remarkable selectivity against SCC-9 cells (squamous cell carcinoma). Compound 10a, in particular, demonstrated exceptional selectivity, making it an excellent choice for cancer cell targeting while sparing healthy cells. Furthermore, complementing in silico and molecular docking studies shed light on their physical features and putative modes of action. This research highlights the potential of these compounds in anticancer treatments and lays the way for future drug development efforts.

17.
Gait Posture ; 111: 59-64, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38643633

RESUMEN

BACKGROUND: Different tasks and proxy measurements have been employed to evaluate dynamic balance in older individuals. However, due to inherent limitations, results from most evaluations could hardly be taken as valid measurements of dynamic balance. RESEARCH QUESTION: Is the Equidyn smartphone application-based protocol valid and sensitive for assessment of dynamic balance in older adults? METHODS: Dynamic balance was evaluated in 52 physically active individuals, age range 60-80 years (M = 69.36). The dynamic tasks were one-leg sway either in the mediolateral (ML) or anteroposterior (AP) direction while supported on the contralateral leg, and cyclic sit-to-stand with a narrow support base. These tasks were performed under standardized movement amplitude and rhythm. Outcomes were correlated with unipedal quiet standing. A smartphone was attached to the trunk backside, and a custom-made application (Equidyn) was employed to provide guidance throughout evaluation, timed beeps to pace the movements, and three-dimensional trunk acceleration measurement for balance evaluation. RESULTS: Our data showed (a) that both ML and AP leg sway tasks were sensitive to aging and to direction of leg sway movements; (b) referenced to quiet unipedal stance, moderate/strong correlations for the ML/AP leg sway tasks and moderate correlations for the sit-to-stand task; and (c) moderate/strong correlations between the ML and AP leg sway tasks, and moderate correlations between the sit-to-stand and the two unipedal dynamic tasks in the ML acceleration direction. SIGNIFICANCE: The current results support the conclusion that the Equidyn protocol is a sensitive and valid tool to evaluate dynamic balance in healthy older individuals. The protocol tasks standardized in amplitude and rhythm favor their reproducibility and trunk acceleration data interpretation. As the whole assessment is made through a smartphone application, this dynamic balance evaluation could be made in a low-cost simple way both in the laboratory and clinical settings.


Asunto(s)
Aplicaciones Móviles , Equilibrio Postural , Teléfono Inteligente , Humanos , Anciano , Equilibrio Postural/fisiología , Masculino , Femenino , Anciano de 80 o más Años , Persona de Mediana Edad , Reproducibilidad de los Resultados , Evaluación Geriátrica/métodos
18.
Environ Monit Assess ; 196(5): 481, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38683240

RESUMEN

The continuous expansion of the global vehicle fleet poses a growing threat to environmental quality through heavy metal contamination. In this scenario, monitoring to safeguard public health in urban areas is necessary. Our study involved the collection of 36 street dust and 29 moss samples from roads of a Brazilian metropolis (Recife) with varying traffic intensities as follows: natural reserve (0 vehicles per day), low (< 15,000 vehicles per day), medium (15,000-30,000 vehicles per day), and high (> 30,000 vehicles per day). ICP-AES analysis was performed to determine the concentrations of nine potentially toxic metals (Ba, Cd, Cr, Cu, Mn, Ni, Pb, V, and Zn) to assess the influence of vehicular flow on urban contamination. In the street dust samples, the mean metal concentrations (mg kg-1) exhibited the following order: Ba (503.7) > Mn (303.0) > Zn (144.4) > Cu (95.3) > Cr (56.1) > Pb (34.2) > V (28.7) > Ni (11.3) > Cd (1.5). Conversely, in the moss samples, the metal concentration order was as follows (mg kg-1): Mn (63.8) > Zn (62.5) > Ba (61.0) > Cu (17.7) > Cr (8.0) > V (7.3) > Pb (7.0) > Ni (2.9) > Cd (0.3). Roads with higher traffic volumes exhibited the highest metal enrichments in moss samples for all metals and in dust samples for Cd, Cr, Mn, Ni, and V. However, dust from low-flow roads had higher enrichments for Ba, Cu, and Zn, indicating the influential role of other traffic-related factors in metal deposition. Our findings highlight traffic flow as the predominant source of pollution in urban centers, with both street dust and moss serving as sensitive indicators of metal input attributable to vehicular traffic. These indicators offer valuable insights for urban quality monitoring and pollution control efforts.


Asunto(s)
Ciudades , Polvo , Monitoreo del Ambiente , Metales Pesados , Metales Pesados/análisis , Brasil , Monitoreo del Ambiente/métodos , Polvo/análisis , Contaminantes Ambientales/análisis , Emisiones de Vehículos/análisis , Contaminantes Atmosféricos/análisis
19.
Chemosphere ; 357: 142074, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38657693

RESUMEN

The objective of this study was to assess the photolysis-mediated degradation of malathion in standard and commercial formulations, and to determine the toxicity of these degraded formulations. Degradation tests were carried out with 500 µg L-1 of malathion and repeated three times. The initial and residual toxicity was assessed by using Lactuca sativa seeds for phytotoxicity, Stegomyia aegypti larvae for acute toxicity, and Stegomyia aegypti mosquitoes (cultivated from the larval stage until emergence as mosquitoes) to evaluate the biochemical markers of sublethal concentrations. For the standard formulations the photolytic process efficiently reduced the initial concentration of malathion to levels below the regulatory limits however, the formation of byproducts was revealed by chromatography, which allowed for a more complete proposal of photolytic-mediated malathion degradation route. The degraded formulations inhibited the growth of L. sativa seeds, while only the untreated formulations showed larvicidal activity and mortality. Both formulations slightly inhibited acetylcholinesterase activity in S. aegypti mosquitoes, while the standard formulation decreased and the commercial formulation increased glutathione S-transferase activity. However, there were no significant differences for superoxide dismutase, esterase-α, esterase-ß and lipid peroxidation. These findings indicate that in the absence of the target compound, the presence of byproducts can alter the enzymatic activity. In general, photolysis effectively degrade malathion lower than the legislation values; however, longer treatment times must be evaluated for the commercial formulation.


Asunto(s)
Insecticidas , Larva , Malatión , Fotólisis , Malatión/química , Malatión/toxicidad , Animales , Insecticidas/química , Insecticidas/toxicidad , Insecticidas/farmacología , Larva/efectos de los fármacos , Aedes/efectos de los fármacos , Aedes/crecimiento & desarrollo , Acetilcolinesterasa/metabolismo , Ecotoxicología , Biomarcadores/metabolismo , Lactuca/efectos de los fármacos , Glutatión Transferasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Superóxido Dismutasa/metabolismo
20.
Cells ; 13(6)2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38534317

RESUMEN

Mitochondria provide energy for all cellular processes, including reactions associated with cell cycle progression, DNA damage repair, and cilia formation. Moreover, mitochondria participate in cell fate decisions between death and survival. Nek family members have already been implicated in DNA damage response, cilia formation, cell death, and cell cycle control. Here, we discuss the role of several Nek family members, namely Nek1, Nek4, Nek5, Nek6, and Nek10, which are not exclusively dedicated to cell cycle-related functions, in controlling mitochondrial functions. Specifically, we review the function of these Neks in mitochondrial respiration and dynamics, mtDNA maintenance, stress response, and cell death. Finally, we discuss the interplay of other cell cycle kinases in mitochondrial function and vice versa. Nek1, Nek5, and Nek6 are connected to the stress response, including ROS control, mtDNA repair, autophagy, and apoptosis. Nek4, in turn, seems to be related to mitochondrial dynamics, while Nek10 is involved with mitochondrial metabolism. Here, we propose that the participation of Neks in mitochondrial roles is a new functional axis for the Nek family.


Asunto(s)
Mitocondrias , Proteínas Serina-Treonina Quinasas , Quinasas Relacionadas con NIMA/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Mitocondrias/metabolismo , Homeostasis , ADN Mitocondrial
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