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1.
Artículo en Inglés | MEDLINE | ID: mdl-39363148

RESUMEN

The overexpression of ATP-binding cassette (ABC) transporters contributes to the failure of chemotherapies and symbolizes a great challenge in oncology, associated with the adaptation of tumor cells to anticancer drugs such that these transporters become less effective, a mechanism known as multidrug resistance (MDR). The aim of this review is to present the most widely used methodologies for induction and comprehension of in vitro models for detection of multidrug-resistant (MDR) modulators or inhibitors, including biochemical and morphological techniques for chemosensitivity studies. The overexpression of MDR proteins, predominantly, the subfamily glycoprotein-1 (P-gp or ABCB1) multidrug resistance, multidrug resistance-associated protein 1 (MRP1 or ABCCC1), multidrug resistance-associated protein 2 (MRP2 or ABCC2) and cancer resistance protein (ABCG2), in chemotherapy-exposed cancer lines have been established/investigated by several techniques. Amongst these techniques, the most used are (i) colorimetric/fluorescent indirect bioassays, (ii) rhodamine and efflux analysis, (iii) release of 3,30-diethyloxacarbocyanine iodide by fluorescence microscopy and flow cytometry to measure P-gp function and other ABC transporters, (iv) exclusion of calcein-acetoxymethylester, (v) ATPase assays to distinguish types of interaction with ABC transporters, (vi) morphology to detail phenotypic characteristics in transformed cells, (vii) molecular testing of resistance-related proteins (RT-qPCR) and (viii) 2D and 3D models, (ix) organoids, and (x) microfluidic technology. Then, in vitro models for detecting chemotherapy MDR cells to assess innovative therapies to modulate or inhibit tumor cell growth and overcome clinical resistance. It is noteworthy that different therapies including anti-miRNAs, antibody-drug conjugates (to natural products), and epigenetic modifications were also considered as promising alternatives, since currently no anti-MDR therapies are able to improve patient quality of life. Therefore, there is also urgency for new clinical markers of resistance to more reliably reflect in vivo effectiveness of novel antitumor drugs.

2.
Antibiotics (Basel) ; 13(9)2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39335027

RESUMEN

Antimicrobial dosing can be a complex challenge. Although a solid rationale exists for a link between antibiotic exposure and outcome, conflicting data suggest a poor correlation between pharmacokinetic/pharmacodynamic targets and infection control. Different reasons may lead to this discrepancy: poor tissue penetration by ß-lactams due to inflammation and inadequate tissue perfusion; different bacterial response to antibiotics and biofilms; heterogeneity of the host's immune response and drug metabolism; bacterial tolerance and acquisition of resistance during therapy. Consequently, either a fixed dose of antibiotics or a fixed target concentration may be doomed to fail. The role of biomarkers in understanding and monitoring host response to infection is also incompletely defined. Nowadays, with the ever-growing stream of data collected in hospitals, utilizing the most efficient analytical tools may lead to better personalization of therapy. The rise of artificial intelligence and machine learning has allowed large amounts of data to be rapidly accessed and analyzed. These unsupervised learning models can apprehend the data structure and identify homogeneous subgroups, facilitating the individualization of medical interventions. This review aims to discuss the challenges of ß-lactam dosing, focusing on its pharmacodynamics and the new challenges and opportunities arising from integrating machine learning algorithms to personalize patient treatment.

3.
bioRxiv ; 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39314333

RESUMEN

Amyotrophic lateral sclerosis (ALS) is an age-related and fatal neurodegenerative disease characterized by progressive muscle weakness. There is marked heterogeneity in clinical presentation, progression, and pathophysiology with only modest treatments to slow disease progression. Molecular markers that provide insight into this heterogeneity are crucial for clinical management and identification of new therapeutic targets. In a prior muscle miRNA sequencing investigation, we identified altered FGF pathways in ALS muscle, leading us to investigate FGF21. We analyzed human ALS muscle biopsy samples and found a large increase in FGF21 expression with localization to atrophic myofibers and surrounding endomysium. A concomitant increase in FGF21 was detected in ALS spinal cords which correlated with muscle levels. FGF21 was increased in the SOD1G93A mouse beginning in presymptomatic stages. In parallel, there was dysregulation of the co-receptor, ß-Klotho. Plasma FGF21 levels were increased and high levels correlated with slower disease progression, prolonged survival, and increased body mass index. In NSC-34 motor neurons and C2C12 muscle cells expressing SOD1G93A or exposed to oxidative stress, ectopic FGF21 mitigated loss of cell viability. In summary, FGF21 is a novel biomarker in ALS that correlates with slower disease progression and exerts trophic effects under conditions of cellular stress.

4.
Entropy (Basel) ; 26(8)2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39202169

RESUMEN

Bio-energy systems with carbon capture and storage (BECCS) will be essential if countries are to meet the gas emission reduction targets established in the 2015 Paris Agreement. This study seeks to carry out a thermodynamic optimization and analysis of a BECCS technology for a typical Brazilian cogeneration plant. To maximize generated net electrical energy (MWe) and carbon dioxide CO2 capture (Mt/year), this study evaluated six cogeneration systems integrated with a chemical absorption process using MEA. A key performance indicator (gCO2/kWh) was also evaluated. The set of optimal solutions shows that the single regenerator configuration (REG1) resulted in more CO2 capture (51.9% of all CO2 emissions generated by the plant), penalized by 14.9% in the electrical plant's efficiency. On the other hand, the reheated configuration with three regenerators (Reheat3) was less power-penalized (7.41%) but had a lower CO2 capture rate (36.3%). Results showed that if the CO2 capture rates would be higher than 51.9%, the cogeneration system would reach a higher specific emission (gCO2/kWh) than the cogeneration base plant without a carbon capture system, which implies that low capture rates (<51%) in the CCS system guarantee an overall net reduction in greenhouse gas emissions in sugarcane plants for power and ethanol production.

5.
Microorganisms ; 12(8)2024 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-39203547

RESUMEN

Sepsis is among the most frequent diagnoses on admission to the intensive care unit (ICU). A systemic inflammatory response, activated by uncontrolled infection, fosters hypoperfusion and multiorgan failure and often leads to septic shock and mortality. These infections arise from a specific anatomic source, and how the infection foci influence the outcomes is unknown. All patients admitted to the ICU of Hospital de Vila Franca de Xira, between 1 January 2017 and 31 June 2023, were screened for sepsis and categorized according to their infection foci. During the study period, 1296 patients (32.2%) had sepsis on admission. Their mean age was 67.5 ± 15.3 and 58.1% were male; 73.0% had community-acquired infections. The lung was the main focus of infection. Septic shock was present in 37.9% of the patients and was associated with hospital mortality. Severe imbalances were noted in its incidence, and there was lower mortality in lung infections. The hospital-acquired infections had a slightly higher mortality but, after adjustment, this difference was non-significant. Patients with secondary bacteremia had a worse prognosis (one-year adjusted hazard ratio of 1.36, 95% confidence interval 1.06-1.74, p = 0.015), especially those with an isolated non-fermenting Gram-negative infection. Lung, skin, and skin structure infections and peritonitis had a worse prognosis, whilst urinary, biliary tract, and other intra-abdominal infections had a better one-year outcome.

6.
Adv Mater ; : e2402988, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39139015

RESUMEN

The inclusion of hollow channels in tissue-engineered hydrogels is crucial for mimicking the natural physiological conditions and facilitating the delivery of nutrients and oxygen to cells. Although bio-fabrication techniques provide diverse strategies to create these channels, many require sophisticated equipment and time-consuming protocols. Herein, collagenase, a degrading agent for methacrylated gelatin hydrogels, and magnetic nanoparticles (MNPs) are combined and processed into enzymatically active spherical structures using a straightforward oil bath emulsion methodology. The generated microgels are then used to microfabricate channels within biomimetic hydrogels via a novel sculpturing approach that relied on the precise coupling of protein-enzyme pairs (for controlled local degradation) and magnetic actuation (for directional control). Results show that the sculpting velocity can be tailored by adjusting the magnetic field intensity or concentration of MNPs within the microgels. Additionally, varying the magnetic field position or microgel size generated diverse trajectories and channels of different widths. This innovative technology improves the viability of encapsulated cells through enhanced medium transport, outperforming non-sculpted hydrogels and offering new perspectives for hydrogel vascularization and drug/biomolecule administration. Ultimately, this novel concept can help design fully controlled channels in hydrogels or soft materials, even those with complex tortuosity, in a single wireless top-down biocompatible step.

7.
Cureus ; 16(7): e63897, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39099977

RESUMEN

BACKGROUND: Along with population aging, frailty is also increasingly common in the intensive care unit (ICU). However, the impact of frailty on the infection incidence, the risk of multidrug-resistant (MDR) microorganisms, and the potential benefits of broad-spectrum antibiotics are still poorly studied. METHODS: This is a multicentric, prospective, observational study collecting data for 15 consecutive days of all consecutive adult patients admitted in each participating ICU. Exclusion criteria included admission for less than 24 hours or failure to obtain informed consent. The Clinical Frailty Score (CFS) was calculated both by the doctor and by the nurse in charge, and the patient's next of kin. Patients were considered frail if the mean of the three measured scores was ≥5. This is a post hoc analysis of the PALliative MUlticenter Study in Intensive Care (PalMuSIC) study. The Hospital de Vila Franca de Xira Ethics Committee approved the study (approval number: 63). RESULTS: A total of 335 patients from 23 Portuguese ICUs were included. Frailty was diagnosed in 20.9%. More than 60% of the patients had a diagnosis of infection during their ICU stay, either present on admission or hospital-acquired. This included 25 (35.7%) frail and 75 (28.3%) non-frail (p=0.23) patients diagnosed with infection. In 34 patients, MDR microorganisms were isolated, which were more common in frail patients (odds ratio (OR): 2.65, 95% confidence interval (CI): 1.3-5.6, p=0.018). Carbapenems were started in 37 (18.1%) patients, but after adjusting for frailty and severity, no clear mortality benefit of this strategy was noted (odds ratio for ICU mortality: 1.61, 95% confidence interval: 0.49-5.31, p=0.43; odds ratio for hospital mortality: 1.61, 95% confidence interval: 0.61-4.21, p=0.33). CONCLUSION: Frail patients had similar rates of infection to non-frail patients but were more prone to have MDR microorganisms as causative pathogens. The use of empirical therapy with large-spectrum antibiotics should be based on microbiological risk factors and not simply on the host characteristics.

8.
J Strength Cond Res ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39178105

RESUMEN

ABSTRACT: Ribeiro, N, Martinho, DV, Pereira, JR, Rebelo, A, Monasterio, X, Gonzalo-Skok, O, Valente-dos-Santos, J, and Tavares, F. Injury risk in elite young male soccer players: a review on the impact of growth, maturation, and workload. J Strength Cond Res XX(X): 000-000, 2024-The long-term development of young male soccer players involves a prolonged period of significant adjustments, highlighting the importance of studying the complex interaction between dynamic variables, including workload, and inherent elements like growth and maturity. This analysis examines the intricate connections involving the development, maturity, workload, and susceptibility to injuries among adolescent male soccer players. Significantly, these connections become prominent at the peak height velocity (PHV) period, a crucial moment in maturation. Growth rates vary among individuals, and higher rates have been associated with an increased risk of injury in young soccer players, particularly during periods of rapid growth. Identifying possible risk factors and understanding the complex connections between them is crucial to developing specific methods for reducing the risk of injury. Sharing this valuable information with essential stakeholders is crucial for guaranteeing young athletes' comprehensive growth and maturation process. Furthermore, this review emphasizes the immediate need for long-term studies and thorough injury analyses to comprehend better the dynamic interactions that influence injury patterns in young male soccer players. This review will allow practitioners to better understand the main modifiable and nonmodifiable risk factors for injury and provide essential information focusing on practical strategies, facilitating more informed decision making by all stakeholders. The review aims to clarify these complexities and offer crucial insights that can assist in designing and implementing efficient strategies to reduce the risk of injury, specifically for the challenges faced during PHV and within the broader framework of long-term athletic development in young soccer.

9.
ACS Omega ; 9(27): 29516-29528, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-39005809

RESUMEN

A heterogenized Mn(III) porphyrin-based catalyst was prepared for dye degradation. The new Mn(III) complex of 5,15-bis(4-aminophenyl)-10,20-diphenylporphyrin was immobilized, via covalent bond, in chloropropyl silica gel, generating the material (Sil-Cl@MnP) with a loading of 23 µmol manganese porphyrin (MnP) per gram of Sil-Cl. This material was used as a catalyst in degradation reactions of model dyes, a cationic dye [methylene blue (MB)] and an anionic dye (reactive red 120, RR120), using PhI(OAc)2 and H2O2 as oxidants. The oxidation reactions were carried out after the dye reached adsorption/desorption equilibrium with the catalytic material, with a much higher percentage of adsorption being observed for the cationic MB dye (20%) than for the anionic RR120 dye (3%), which may be associated with electrostatic attraction or repulsion effects, respectively, with the negatively charged surface of the silica (zeta potential measurement for Sil-Cl@MnP, ζ = -19.2 mV). In general, there was a higher degradation percentage for MB than for RR120, probably because the size and charge of RR120 would hinder its approach to the MnP active species on the silica surface. With respect to the oxidant, the PhI(OAc)2-based systems showed a higher degradation percentage than those of H2O2. It was observed that the increase in the oxidant concentration promoted a significant increase in the degradation of MB, with a degradation of approximately 65%. The efficiency of the catalyst was also evaluated after successive additions of the oxidant every 2 h, and it can be seen that the catalyst had no loss of efficiency, with a degradation percentage greater than 80% being observed after 8 h of reaction. The phytotoxicity of the products formed in the system was evaluated in a 1:23.5:188 molar ratio Sil-Cl@MnP: MB:PhI(OAc)2 was used. In these studies, phytotoxicity was found for the germination of lettuce seeds when the original solution was used without dilution; however, when diluted (10% V/V), the results were close to the positive and negative controls. Thus, the material obtained proved to be a potential candidate for application in the degradation reactions of environmental pollutants.

10.
EBioMedicine ; 106: 105248, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39018756

RESUMEN

BACKGROUND: The ubiquitin regulatory X (UBX) domain-containing proteins (UBXNs) are putative adaptors for ubiquitin ligases and valosin-containing protein; however, their in vivo physiological functions remain poorly characterised. We recently showed that UBXN3B is essential for activating innate immunity to DNA viruses and controlling DNA/RNA virus infection. Herein, we investigate its role in adaptive immunity. METHODS: We evaluated the antibody responses to multiple viruses and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza in tamoxifen-inducible global and constitutive B cell-specific Ubxn3b knockout mice; quantified various immune populations, B lineage progenitors/precursors, B cell receptor (BCR) signalling and apoptosis by flow cytometry, immunoblotting and immunofluorescence microscopy. We also performed bone marrow transfer, single-cell and bulk RNA sequencing. FINDINGS: Both global and B cell-specific Ubxn3b knockout mice present a marked reduction in small precursor B-II (>60%), immature (>70%) and mature B (>95%) cell numbers. Transfer of wildtype bone marrow to irradiated global Ubxn3b knockouts restores normal B lymphopoiesis, while reverse transplantation does not. The mature B population shrinks rapidly with apoptosis and higher pro and activated caspase-3 protein levels were observed following induction of Ubxn3b knockout. Mechanistically, Ubxn3b deficiency leads to impaired pre-BCR signalling and cell cycle arrest. Ubxn3b knockout mice are highly vulnerable to respiratory viruses, with increased viral loads and prolonged immunopathology in the lung, and reduced production of virus-specific IgM/IgG. INTERPRETATION: UBXN3B is essential for B lymphopoiesis by maintaining constitutive pre-BCR signalling and cell survival in a cell-intrinsic manner. FUNDING: United States National Institutes of Health grants, R01AI132526 and R21AI155820.


Asunto(s)
Linfocitos B , Linfopoyesis , Ratones Noqueados , Animales , Linfopoyesis/genética , Ratones , Linfocitos B/inmunología , Linfocitos B/metabolismo , COVID-19/inmunología , SARS-CoV-2/fisiología , Transducción de Señal , Apoptosis , Receptores de Antígenos de Linfocitos B/metabolismo , Humanos
11.
JHEP Rep ; 6(7): 101069, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38966234

RESUMEN

Background & Aims: The lymphatic system plays crucial roles in maintaining fluid balance and immune regulation. Studying the liver lymphatics has been considered challenging, as common lymphatic endothelial cell (LyEC) markers are expressed by other liver cells. Additionally, isolation of sufficient numbers of LyECs has been challenging because of their extremely low abundance (<0.01% of entire liver cell population) in a normal liver. Methods: Potential LyEC markers was identified using our published single-cell RNA sequencing (scRNA-seq) dataset (GSE147581) in mouse livers. Interleukin-7 (IL7) promoter-driven green fluorescent protein knock-in heterozygous mice were used for the validation of IL7 expression in LyECs in the liver, for the development of liver LyEC isolation protocol, and generating liver ischemia/reperfusion (I/R) injury. Scanning electron microscopy was used for the structural analysis of LyECs. Changes in LyEC phenotypes in livers of mice with I/R were determined by RNA-seq analysis. Results: Through scRNA-seq analysis, we have identified IL7 as an exclusive marker for liver LyECs, with no overlap with other liver cell types. Based on IL7 expression in liver LyECs, we have established an LyEC isolation method and observed distinct cell surface structures of LyECs with fenestrae and cellular pores (ranging from 100 to 400 nm in diameter). Furthermore, we identified LyEC genes that undergo alterations during I/R liver injuries. Conclusions: This study not only identified IL7 as an exclusively expressed gene in liver LyECs, but also enhanced our understanding of LyEC structures and demonstrated transcriptomic changes in injured livers. Impact and implications: Understanding the lymphatic system in the liver is challenging because of the absence of specific markers for liver LyEC. This study has identified IL7 as a reliable marker for LyECs, enabling the development of an effective method for their isolation, elucidating their unique cell surface structure, and identifying LyEC genes that undergo changes during liver damage. The development of IL7 antibodies for detecting it in human liver specimens will further advance our understanding of the liver lymphatic system in the future.

12.
J Hazard Mater ; 477: 135324, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39068890

RESUMEN

Plastic pollution poses a significant threat to marine ecosystems. Microfibres from fabrics have become the most prevalent shape of microplastic found in the marine environment. The northern krill (Meganyctiphanes norvegica) is the most abundant euphausiid species in the northern hemisphere, playing a crucial role in various pelagic ecosystems. Anthropogenic microparticles in northern krill was assessed for the first time in samples collected in the Azores on two occasions - April 2019 (n = 480) and April 2023 (n = 480). Analysis of all individuals revealed 533 anthropogenic particles, with an average abundance of 0.56 ± 0.14 items per individual and, no significant differences between years. Microfibres were the most common shape (94.8 %), with the remaining items being fragments (5.2 %), and blue and black were the predominant colours. MicroFourier transform infrared spectroscopy analysis (µFTIR) of 22.1 % of the total number of particles, showed that they were mainly cellulosic (65.3 %) - either natural or semisynthetic - followed by polyester (7.6 %). Our finding of microplastics in the northern krill raises important questions due to its crucial role in marine food webs. The intake of anthropogenic particles, particularly those that are 100 % synthetic, suggests that the northern krill may act as a transfer vector of these pollutants to higher trophic levels.


Asunto(s)
Euphausiacea , Cadena Alimentaria , Animales , Azores , Contaminantes Químicos del Agua/análisis , Microplásticos/análisis , Monitoreo del Ambiente
13.
J Clin Invest ; 134(16)2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38916955

RESUMEN

Neutrophil infiltration occurs in a variety of liver diseases, but it is unclear how neutrophils and hepatocytes interact. Neutrophils generally use granule proteases to digest phagocytosed bacteria and foreign substances or neutralize them in neutrophil extracellular traps. In certain pathological states, granule proteases play a destructive role against the host as well. More recently, nondestructive actions of neutrophil granule proteins have been reported, such as modulation of tissue remodeling and metabolism. Here, we report a completely different mechanism by which neutrophils act nondestructively, by inserting granules directly into hepatocytes. Specifically, elastase-containing granules were transferred to hepatocytes where elastase selectively degraded intracellular calcium channels to reduce cell proliferation without cytotoxicity. In response, hepatocytes increased expression of Serpin E2 and A3, which inhibited elastase activity. Elastase insertion was seen in patient specimens of alcohol-associated hepatitis, and the relationship between elastase-mediated ITPR2 degradation and reduced cell proliferation was confirmed in mouse models. Moreover, neutrophils from patients with alcohol-associated hepatitis were more prone to degranulation and more potent in reducing calcium channel expression than neutrophils from healthy individuals. This nondestructive and reversible action on hepatocytes defines a previously unrecognized role for neutrophils in the transient regulation of epithelial calcium signaling mechanisms.


Asunto(s)
Señalización del Calcio , Hepatitis Alcohólica , Hepatocitos , Neutrófilos , Elastasa Pancreática , Humanos , Neutrófilos/metabolismo , Neutrófilos/patología , Animales , Ratones , Hepatocitos/metabolismo , Hepatocitos/patología , Hepatitis Alcohólica/metabolismo , Hepatitis Alcohólica/patología , Hepatitis Alcohólica/genética , Elastasa Pancreática/metabolismo , Masculino , Proliferación Celular , Canales de Calcio/metabolismo , Canales de Calcio/genética , Femenino
14.
Metab Brain Dis ; 39(5): 915-928, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38836947

RESUMEN

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease globally, with a fast-growing prevalence. The etiology of PD exhibits a multifactorial complex nature and remains challenging. Herein, we described clinical, molecular, and integrative bioinformatics findings from a Brazilian female affected by Early-Onset PD (EOPD) harboring a recurrent homozygous pathogenic deletion in the parkin RBR E3 ubiquitin protein ligase gene (PRKN; NM_004562.3:c.155delA; p.Asn52Metfs*29; rs754809877), along with a novel heterozygous variant in the synaptojanin 1 gene (SYNJ1; NM_003895.3:c.62G > T; p.Cys21Phe; rs1486511197) found by Whole Exome Sequencing. Uncommon or unreported PRKN-related clinical features in the patient include cognitive decline, auditory and visual hallucinations, REM sleep disorder, and depression, previously observed in SYNJ1-related conditions. Moreover, PRKN interacts with endophilin A1, which is a major binding partner of SYNJ1. This protein plays a pivotal role in regulating the dynamics of synaptic vesicles, particularly in the context of endocytosis and recycling processes. Altogether, our comprehensive analyses underscore a potential synergistic effect between the PRKN and SYNJ1 variants over the pathogenesis of EOPD.


Asunto(s)
Enfermedad de Parkinson , Ubiquitina-Proteína Ligasas , Humanos , Enfermedad de Parkinson/genética , Femenino , Ubiquitina-Proteína Ligasas/genética , Adulto , Edad de Inicio , Proteínas del Tejido Nervioso/genética , Monoéster Fosfórico Hidrolasas
15.
JCI Insight ; 9(14)2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38888971

RESUMEN

A defining feature of systemic lupus erythematosus (SLE) is loss of tolerance to self-DNA, and deficiency of DNASE1L3, the main enzyme responsible for chromatin degradation in blood, is also associated with SLE. This association can be found in an ultrarare population of pediatric patients with DNASE1L3 deficiency who develop SLE, adult patients with loss-of-function variants of DNASE1L3 who are at a higher risk for SLE, and patients with sporadic SLE who have neutralizing autoantibodies against DNASE1L3. To mitigate the pathogenic effects of inherited and acquired DNASE1L3 deficiencies, we engineered a long-acting enzyme biologic with dual DNASE1/DNASE1L3 activity that is resistant to DNASE1 and DNASE1L3 inhibitors. Notably, we found that the biologic prevented the development of lupus in Dnase1-/-Dnase1L3-/- double-knockout mice and rescued animals from death in pristane-induced lupus. Finally, we confirmed that the human isoform of the enzyme biologic was not recognized by autoantibodies in SLE and efficiently degraded genomic and mitochondrial cell-free DNA, as well as microparticle DNA, in SLE plasma. Our findings suggest that autoimmune diseases characterized by aberrant DNA accumulation, such as SLE, can be effectively treated with a replacement DNASE tailored to bypass pathogenic mechanisms, both genetic and acquired, that restrict DNASE1L3 activity.


Asunto(s)
Autoinmunidad , Desoxirribonucleasa I , Modelos Animales de Enfermedad , Endodesoxirribonucleasas , Lupus Eritematoso Sistémico , Ratones Noqueados , Animales , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/genética , Ratones , Endodesoxirribonucleasas/genética , Endodesoxirribonucleasas/metabolismo , Humanos , Desoxirribonucleasa I/metabolismo , Desoxirribonucleasa I/genética , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Femenino
16.
Mar Drugs ; 22(6)2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38921565

RESUMEN

The microalgae Chlorella vulgaris and Tetraselmis chui are valued for their nutrient-rich content, including lipids and polyunsaturated fatty acids (PUFA). However, little is known about how storage and processing affect their lipid quality. This study aimed to assess the impact of domestic storage and cooking practices in dried biomass of C. vulgaris and T. chui. Four conditions were tested: control (newly opened package), light (storage at room temperature and daily light regimen for three weeks), frozen (storage in the freezer at -20 °C for three weeks), and heated (three cycles of 90 min at 100 °C). Lipid extracts were analyzed by GC-MS and LC-MS, and antioxidant activity through DPPH and ABTS radical scavenging assays. Tested storage conditions promoted a decrease in fatty acid content and in diacyl/lyso lipid species ratios of phospholipid (PC/LPC, PE/LPE) and betaine lipids (DGTS/MGTS). Lipid extracts from light treatment showed the lowest antioxidant activity in C. vulgaris (ABTS, IC40: 104.9; DPPH, IC20: 187.9 ± 15.0), while heat affected the antioxidant activity of T. chui (ABTS, IC40: 88.5 ± 2.8; DPPH, IC20 209.4 ± 10.9). These findings underscore the impact of managing storage and processing conditions to optimize the nutritional and functional benefits of C. vulgaris and T. chui in food and feed applications.


Asunto(s)
Antioxidantes , Chlorella vulgaris , Microalgas , Antioxidantes/farmacología , Chlorella vulgaris/química , Microalgas/química , Lípidos , Almacenamiento de Alimentos , Ácidos Grasos/análisis , Culinaria
17.
Sci Total Environ ; 945: 173932, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38880133

RESUMEN

Bio-electrochemical systems (BESs) have recently been proposed as an efficient treatment technology to remove organic micropollutants from water treatment plants. In this study, we aimed to differentiate between sorption, electrochemical transport/degradation, and biodegradation. Using electro-active microorganisms and electrodes, we investigated organic micropollutant removal at environmentally relevant concentrations, clarifying the roles of sorption and electrochemical and biological degradation. The role of anodic biofilms on the removal of 10 relevant organic micropollutants was studied by performing separate sorption experiments on carbon-based electrodes (graphite felt, graphite rod, graphite granules, and granular activated carbon) and electrochemical degradation experiments at two different electrode potentials (-0.3 and 0 V). Granular activated carbon showed the highest sorption of micropollutants; applying a potential to graphite felt electrodes increased organic micropollutant removal. Removal efficiencies >80 % were obtained for all micropollutants at high anode potentials (+0.955 V), indicating that the studied compounds were more susceptible to oxidation than to reduction. All organic micropollutants showed removal when under bio-electrochemical conditions, ranging from low (e.g. metformin, 9.3 %) to exceptionally high removal efficiencies (e.g. sulfamethoxazole, 99.5 %). The lower removal observed under bio-electrochemical conditions when compared to only electrochemical conditions indicated that sorption to the electrode is key to guarantee high electrochemical degradation. The detection of transformation products of chloridazon and metformin indicated that (bio)-electrochemical degradation occurred. This study confirms that BES can treat some organic micropollutants through several mechanisms, which merits further investigation.


Asunto(s)
Biodegradación Ambiental , Técnicas Electroquímicas , Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/análisis , Eliminación de Residuos Líquidos/métodos , Biopelículas , Electrodos , Purificación del Agua/métodos , Adsorción
18.
Cureus ; 16(4): e57705, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38711707

RESUMEN

The worldwide mass vaccination campaign against COVID-19 has been the largest one ever undertaken. Although the short-term safety profile of the different vaccines has been well established, neuroinflammatory complications have been described, including rare cases of acute demyelinating inflammatory polyneuropathy. We report a 63-year-old man who presented to the emergency department with proximal muscle weakness and paresthesia. He had received the first dose of the AZD1222 SARS-CoV-2 vaccine (Oxford, AstraZeneca) two weeks before presentation. The diagnosis of Guillain-Barré syndrome (GBS) was confirmed by clinical features, cerebrospinal fluid analysis, and electromyography. On the second hospital day, progression to flaccid tetraplegia, cranial nerve involvement, and respiratory failure, requiring invasive mechanical ventilation, were noted, and he was admitted to the intensive care unit. Despite the prompt diagnosis and immunosuppressive treatment initiation, the patient was left with severe disability. Although the COVID-19 vaccination was generally safe and socially beneficial, individual adverse reactions, including neuroinflammatory severe complications, may occur.

19.
Int J Sports Physiol Perform ; 19(7): 696-704, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38772546

RESUMEN

PURPOSE: This cohort study aimed to investigate the relationship between subjective (wellness and internal training load [ITL]) and objective (neuromuscular fatigue) monitoring markers and performance aspects (reception quality [RQ] and attack efficiency [AE]) in professional female volleyball players. METHODS: The study was conducted over an 8-week period during the final mesocycle of the competitive phase. A total of 24 training sessions and 10 matches were included in the analysis. Subjective measures of wellness and ITL were assessed, and neuromuscular fatigue was evaluated using countermovement-jump (CMJ) height. RQ and AE were determined based on game statistics. RESULTS: The study found a positive relationship between wellness and RQ, particularly affecting outside hitters and liberos. ITL showed a positive association with AE, primarily impacting outside hitters, opposite hitters, and middle blockers. Additionally, ITL demonstrated a negative correlation with RQ, mainly affecting outside hitters and liberos. CMJ performance was associated with AE, where a decrease in CMJ height was linked to reduced AE. CONCLUSIONS: The findings highlight the importance of considering players' wellness scores in training and match strategies for different positions. Careful management of training loads, considering both physical and technical demands, is crucial for optimizing performance outcomes. Monitoring neuromuscular fatigue, as indicated by CMJ performance, is particularly relevant for outside hitters, opposite hitters, and middle blockers involved in attack actions. Coaches, trainers, and sports practitioners can use these insights to develop position-specific training protocols and implement effective strategies for maintaining or improving performance metrics under various stressors.


Asunto(s)
Rendimiento Atlético , Fatiga Muscular , Voleibol , Humanos , Femenino , Voleibol/fisiología , Rendimiento Atlético/fisiología , Fatiga Muscular/fisiología , Adulto Joven , Acondicionamiento Físico Humano/métodos , Conducta Competitiva/fisiología , Adulto , Estado de Salud , Estudios de Cohortes
20.
J Clin Med ; 13(10)2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38792453

RESUMEN

Background/Objective: To ensure that implants are able to support prosthetic rehabilitation, a stable and functional union between the bone and the implant surface is crucial to its stability and success. To increase bone volume and density and excel bone-implant contact, a novel drilling method, called osseodensification (OD), was performed. To assess the effectiveness of the osseodensification drilling protocol versus the conventional surgical technique on implant stability. Methods: Bone Level Tapered Straumann implants were placed side-by-side with both OD and subtractive conventional drilling (SD) in 90 patients from CESPU-Famalicão clinical unit. IT was measured using a manual torque wrench, and the Implant stability quotient (ISQ) value was registered using the Osstell® IDX. Results: According to the multifactorial ANOVA, there were statistically significant differences in the mean IT values due to the arch only (F(1.270) = 4.702, p-value = 0.031 < 0.05). Regarding the length of the implant, there were statistically significant differences in the mean IT in the OD group (p = 0.041), with significantly lower mean IT values for the Regular implants compared to the Long. With respect to the arch, the analyses of the overall ISQ values showed an upward trend in both groups in the maxilla and mandible. High levels of IT also showed high ISQ values, which represent good indicators of primary stability. Conclusions: OD does not have a negative influence on osseointegration compared to conventional subtractive osteotomy.

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