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1.
Lancet Microbe ; : 100948, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39243797

RESUMO

Although microbiome signatures have been identified in various contexts (ie, pathogenesis of non-communicable diseases and treatment response), qualified microbiome-based biomarkers are currently not in use in clinical practice. The Human Microbiome Action consortium initiated a Delphi survey to establish a consensus on the needs, challenges, and limitations in developing qualified microbiome-based biomarkers. The questionnaire was developed by a scientific committee via literature review and expert interviews. To ensure broad applicability of the results, 307 experts were invited to participate; 114 of them responded to the first round of the survey, 93 of whom completed the second and final round as well. The survey highlighted the experts' confidence in the potential of microbiome-based biomarkers for several indications or pathologies. The paucity of validated analytical methods appears to be the principal factor hindering the qualification of these biomarkers. The survey also showed that clinical implementation of these biomarkers would only be possible if kitted and validated molecular assays with simple interpretation are developed. This initiative serves as a foundation for designing and implementing public-private collaborative projects to overcome the challenges and promote clinical application of microbiome-based biomarkers.

2.
Int J Phytoremediation ; : 1-9, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39277799

RESUMO

The effectiveness of phytoremediation in Cd-contaminated soils is crucial for enhancing nutrient availability and plant tolerance to Cd. We simulated soil contamination with varying textures and fertilization conditions. Two experiments were conducted: one without liming and fertilization and another with soil fertilization for grasses. The soil types used were Oxisol and Entisol, and the grasses tested were Megathyrsus maximus and Urochloa brizantha at three Cd levels: 0 mg kg-1 (Control), 2 mg kg-1 (Low), and 12 mg kg-1 (High). Soil amendments and fertilization did not significantly change Cd availability. Soil chemical attributes were unaffected by Cd contamination but were influenced by fertilization, which kept the pH below optimal levels. Cd availability was higher in more contaminated soils, with Entisol showing greater concentrations than Oxisol. Dry matter production of the grasses decreased with higher contamination, with U. brizantha being more productive than M. maximus in fertilized soils. Cd accumulation was higher in highly contaminated soils, particularly for U. brizantha. The bioconcentration factor was higher in Entisol, while the translocation factor exceeded 1.0 only for M. maximus in low-contamination Oxisol. Fertilization can mitigate Cd contamination effects, with U. brizantha showing greater tolerance and accumulation capacity in fertilized soils.


Grasses, often seen just as cover crops or forages, can play a vital role in mitigating heavy metal pollution, especially Cd. By comparing the growth, Cd accumulation, and tolerance of different grass species in fertilized versus unfertilized soils, we identify optimal strategies to maximize the effectiveness of phytoremediation without compromising soil health and ecological balance. The findings of the study reveal that the response of grasses to fertilization in contaminated soils varies significantly, directly influencing their capacity to phytoremediate Cd. This discovery suggests that customizing fertilizer use, based on the grass species and specific soil conditions, could be crucial for optimizing the removal of Cd from the environment.

3.
Prep Biochem Biotechnol ; : 1-7, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39222362

RESUMO

Proteases are enzymes that hydrolyze peptide bonds present in proteins and peptides. They are widely used for various industrial applications, such as in the detergent, food, and dairy industries. Cheese is one of the most important products of the dairy industry, and the coagulation stage is crucial during the cheese-making process. Enzymatic coagulation is the most common technique utilized for this purpose. Microbial enzymes are frequently used for coagulation due to their advantages in terms of availability, sustainability, quality control, product variety, and compliance with dietary and cultural/religious requirements. In the present study, we identified and subsequently characterized milk coagulant activity from the fungus Pleurotus djamor PLO13, obtained during a solid-state fermentation process, using the agro-industrial residue, wheat bran, as the fermentation medium. Maximum enzyme production and caseinolytic activity occurred 120 h after cultivation. When the enzyme activity against various protease-specific synthetic substrates and inhibitors was analyzed, the enzyme was found to be a serine protease, similar to elastase 2. This elastase-2-like serine protease was able to coagulate pasteurized whole and reconstituted skim milk highly efficiently in the presence and absence of calcium, even at room temperature. The coagulation process was influenced by factors such as temperature, time, and calcium concentration. We demonstrate here, for the first time, an elastase-2-like enzyme in a microorganism and its potential application in the food industry for cheese production.

4.
J Biomed Mater Res B Appl Biomater ; 112(9): e35478, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39223072

RESUMO

Despite the numerous studies on biocompatibility with nano-biomaterials, the biological effects of strontium-substituted HA nanoparticles (nSrHA) need to be better understood. So, we conducted an embryotoxicity test using zebrafish (Danio rerio) according to the OECD 236 guideline, a model that represents a viable alternative that bridges the gap between in vitro and mammalian models. Zebrafish embryos were exposed for 120 h to microspheres containing nSrHA nanoparticles with low and high crystallinity, synthesized at temperatures of 5°C (nSrHA5) and 90°C (nSrHA90). We evaluated lethality, developmental parameters, and reactive oxygen species (ROS) production. The larval behavior was assessed at 168 hpf to determine if the biomaterials affected motor responses and anxiety-like behavior. The results showed that the survival rate decreased significantly for the nSrHA5 group (low crystalline particles), and an increase in ROS was also observed in this group. However, none of the biomaterials caused morphological changes indicative of toxicity during larval development. Additionally, the behavioral tests did not reveal any alterations in all experimental groups, indicating the absence of neurotoxic effects from exposure to the tested biomaterials. These findings provide valuable insights into the biosafety of modified HA-based nanostructured biomaterials, making them a promising strategy for bone tissue repair. As the use of hydroxyapatite-based biomaterials continues to grow, it is crucial to ensure rigorous control over the quality, reliability, and traceability of these materials.


Assuntos
Estrôncio , Peixe-Zebra , Animais , Estrôncio/química , Estrôncio/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Teste de Materiais , Hidroxiapatitas/química , Hidroxiapatitas/farmacologia , Nanoestruturas/química , Larva/efeitos dos fármacos
5.
Int J Pharm ; 665: 124696, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39265853

RESUMO

Advances in gene therapy, exemplified by mRNA vaccines against COVID-19, highlight the importance of lipid nanoparticles (LNPs) for nucleic acid delivery despite challenging storage conditions. Substituting mRNA with pDNA in LNPs may enhance stability and efficacy, yet maintaining LNP stability poses challenges, particularly during freeze-drying. Cryoprotectants offer potential to mitigate destabilization, improving LNP properties and in vivo performance. Here, we evaluated the effects of different concentrations of various cryoprotectants on the freeze-drying process of pDNA-loaded LNPs, assessing their physicochemical characteristics and transfection efficiency. Stability was examined under various storage conditions, confirming biological efficacy post-storage. Our results highlight the role of cryoprotectants in optimizing freeze-drying for the extended shelf life of nucleic acid-loaded LNPs. Trehalose emerged as an efficient cryoprotectant, maintaining LNP stability after the freeze-drying process for up to 2 years, with diameters and transfection efficiency comparable to fresh formulations. These findings demonstrate the optimized concentration of cryoprotectants to sustain LNP stability despite freeze-drying and prolonged storage, providing valuable insights for nucleic acid-based therapies.


Assuntos
Crioprotetores , DNA , Liofilização , Lipídeos , Nanopartículas , Plasmídeos , Transfecção , Trealose , Transfecção/métodos , Nanopartículas/química , Lipídeos/química , Trealose/química , Plasmídeos/administração & dosagem , Crioprotetores/química , DNA/administração & dosagem , DNA/química , Humanos , Estabilidade de Medicamentos , Lipossomos
6.
Inflammopharmacology ; 32(5): 3389-3398, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39126571

RESUMO

Syagrus coronata, a native palm tree in the Caatinga domain, produces fixed oil (ScFO) used therapeutically and dietary by Northeast Brazilian communities. This study evaluated its anti-inflammatory potential of CFA-induced arthritis and its effect on behavioral parameters. In the acute model, ScFO at 25, 50, and 100 mg/kg showed edematogenic effects similar to indomethacin at 4 mg/kg (p > 0.05). In the arthritis model, 100 mg/kg ScFO treatment was comparable to indomethacin (4 mg/kg) (p > 0.05). TNF-α and IL-1ß levels were significantly reduced in ScFO-treated groups at 25, 50, and 100 mg/kg, and the indomethacin group (4 mg/kg) versus the positive control (p > 0.05). Radiographs showed severe soft-tissue swelling and bone deformities in the control group, while the 100 mg/kg ScFO group had few alterations, similar to the indomethacin group. Histopathological analysis revealed intense lymphocytic infiltration in the control group, mild diffuse lymphocytic infiltration in the indomethacin group, and mild lymphoplasmacytic infiltration with focal polymorphonuclear infiltrates in the 100 mg/kg ScFO group. Behavioral analysis showed improved exploratory stimuli in ScFO and indomethacin-treated mice compared to the positive control (p > 0.05). ScFO demonstrated anti-inflammatory effects in both acute and chronic arthritis models, reducing edema and pro-inflammatory cytokines, and improved exploratory behavior due to its analgesic properties.


Assuntos
Anti-Inflamatórios , Artrite Experimental , Adjuvante de Freund , Animais , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Camundongos , Anti-Inflamatórios/farmacologia , Masculino , Óleos de Plantas/farmacologia , Arecaceae/química , Edema/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-1beta/metabolismo , Óleo de Palmeira/farmacologia , Indometacina/farmacologia , Brasil , Relação Dose-Resposta a Droga
7.
Vaccines (Basel) ; 12(8)2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39203974

RESUMO

Cancer patients, prone to severe COVID-19, face immune challenges due to their disease and treatments. Identifying biomarkers, particularly extracellular vesicle (EV)-derived microRNAs (miRNAs), is vital for comprehending their response to COVID-19 vaccination. Therefore, this study aimed to investigate specific EV-miRNAs in the plasma of cancer patients under active treatment who received the COVID-19 booster vaccine. The selected miRNAs (EV-hsa-miR-7-5p, EV-hsa-miR-15b-5p, EV-hsa-miR-24-3p, EV-hsa-miR-145- 5p, and EV-hsa-miR-223-3p) are involved in regulating SARS-CoV-2 spike protein and cytokine release, making them potential biomarkers for vaccination response. The study involved 54 cancer patients. Plasma and serum samples were collected at pre-boost vaccination, and at 3 and 6 months post-boost vaccination. Anti-spike antibody levels were measured. Additionally, RNA was extracted from EVs isolated from plasma and the expression levels of miRNAs were assessed. The results showed a significantly positive antibody response after COVID-19 boost vaccination. The expression levels of EV-hsa-miR-7-5p, EV-hsa-miR-15b-5p, EV-hsa-miR-24-3p, and EV-hsa-miR-223-3p increased significantly after 6 months of COVID-19 booster vaccination. Interestingly, an increased expression of certain EV-hsa-miRNAs was positively correlated. Bioinformatic analysis revealed that these correlated miRNAs play a critical role in regulating the targets present in antiviral responses and cytokine production. These findings suggest that EV-hsa-miR-15b-5p, EV-hsa-miR-24-3p, and EV-hsa-miR-223-3p may be crucial in immune response induced by mRNA vaccines.

8.
Sci Transl Med ; 16(760): eadl0715, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39141698

RESUMO

Extracellular acyl-coenzyme A binding protein [ACBP encoded by diazepam binding inhibitor (DBI)] is a phylogenetically ancient appetite stimulator that is secreted in a nonconventional, autophagy-dependent fashion. Here, we show that low ACBP/DBI plasma concentrations are associated with poor prognosis in patients with anorexia nervosa, a frequent and often intractable eating disorder. In mice, anorexia induced by chronic restraint stress (CRS) is accompanied by a reduction in circulating ACBP/DBI concentrations. We engineered a chemical-genetic system for the secretion of ACBP/DBI through a biotin-activatable, autophagy-independent pathway. In transgenic mice expressing this system in hepatocytes, biotin-induced elevations in plasma ACBP/DBI concentrations prevented anorexia induced by CRS or chemotherapeutic agents including cisplatin, doxorubicin, and paclitaxel. ACBP/DBI reversed the CRS or cisplatin-induced increase in plasma lipocalin-2 concentrations and the hypothalamic activation of anorexigenic melanocortin 4 receptors, for which lipocalin-2 is an agonist. Daily intravenous injections of recombinant ACBP/DBI protein or subcutaneous implantation of osmotic pumps releasing recombinant ACBP/DBI mimicked the orexigenic effects of the chemical-genetic system. In conclusion, the supplementation of extracellular and peripheral ACBP/DBI might constitute a viable strategy for treating anorexia.


Assuntos
Anorexia , Inibidor da Ligação a Diazepam , Animais , Inibidor da Ligação a Diazepam/metabolismo , Anorexia/tratamento farmacológico , Anorexia/metabolismo , Humanos , Camundongos Transgênicos , Camundongos , Anorexia Nervosa/metabolismo , Anorexia Nervosa/tratamento farmacológico , Lipocalina-2/metabolismo , Lipocalina-2/sangue , Hipotálamo/metabolismo , Masculino , Feminino , Camundongos Endogâmicos C57BL , Restrição Física , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos
9.
Vaccine ; 42(25): 126114, 2024 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-39019656

RESUMO

We aimed to characterise vaccine-induced protection against COVID-19 during five waves caused by Variants of Concern (VOCs). This is a nested case-control study of 3,972 HCW primarily vaccinated with CoronaVac (98%) that evaluated symptomatic SARS-CoV-2 breakthrough infections (BI) in almost two-years follow-up until the 3rd Omicron wave. Predictors of protection against SARS-CoV-2 BI were analysed using conditional logistic regression models. We included 1,491 SARS-CoV-2 breakthrough cases, mostly mild, and 2,962 controls. Most participants (90%) had received at least one booster before the onset of the Omicron waves, mainly BNT162b2. A multivariate logistic regression showed that vaccine-induced protection against BI wanes after six months regardless of the number of monovalent booster doses. Additionally, booster dose with BNT162b2 showed a trend for higher protection compared to CoronaVac during the Omicron waves. In conclusion, immunity of monovalent booster doses against SARS-CoV-2 is short-lasting. Individuals previously vaccinated with an inactivated vaccine should receive a BNT162B2 booster dose.


Assuntos
Vacina BNT162 , Vacinas contra COVID-19 , COVID-19 , Pessoal de Saúde , Imunização Secundária , SARS-CoV-2 , Humanos , COVID-19/prevenção & controle , COVID-19/imunologia , Masculino , Pessoal de Saúde/estatística & dados numéricos , Feminino , Pessoa de Meia-Idade , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , SARS-CoV-2/imunologia , Adulto , Estudos de Casos e Controles , Vacina BNT162/imunologia , Vacina BNT162/administração & dosagem , Vacinação , Idoso , Infecções Irruptivas , Vacinas de Produtos Inativados
10.
J Trace Elem Med Biol ; 86: 127499, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39084121

RESUMO

INTRODUCTION: Chronic low-grade inflammation and oxidative stress are pivotal contributors to the metabolic complications associated with obesity. Selenoprotein P (SELENOP) and glutathione peroxidase 1 (GPx1) are selenoproteins involved in the reduction of reactive oxygen species and pro-inflammatory cytokines levels. Nutritional epigenomics revealed the interaction of microRNAs and nutrients with an important impact on metabolic pathways involved in obesity. However, the knowledge regarding the influence of microRNA on selenium biomarkers and its impact on metabolic pathways related to obesity remains scarce. Thus, the aim of this study was to investigate the association of plasma miR-7-5p expression with selenium and inflammatory biomarkers in women with overweight/obesity. MATERIAL AND METHODS: Anthropometric evaluations were performed and blood samples were collected for the analysis of fasting glucose, insulin, inflammatory and selenium biomarkers, and miR-7-5p expression in 54 women with overweight/obesity. Gene expression of SELENOP and GPX1 were evaluated in peripheral mononuclear blood cells. RESULTS: This study observed a negative correlation between SELENOP levels and miR-7-5p (rho = -0.350; p = 0.018). Additionally, it was observed that body fat (OR = 0.737; p = 0.011), age (OR = 1.214; p = 0.007), and miR-7-5p (OR = 0.990; p = 0.015) emerged as significant predictors of SELENOP levels. CONCLUSIONS: In conclusion, we observed a significant inverse association between miR-7-5p expression and SELENOP concentration in overweight/obese women, suggesting that age and percentage of body fat are also associated. TRIAL REGISTRATION NUMBER: Brazilian Registry of Clinical Trials (ReBEC) number RBR-2nfy5q.

11.
Nat Med ; 30(8): 2170-2180, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38942992

RESUMO

Metastasis occurs frequently after resection of pancreatic cancer (PaC). In this study, we hypothesized that multi-parametric analysis of pre-metastatic liver biopsies would classify patients according to their metastatic risk, timing and organ site. Liver biopsies obtained during pancreatectomy from 49 patients with localized PaC and 19 control patients with non-cancerous pancreatic lesions were analyzed, combining metabolomic, tissue and single-cell transcriptomics and multiplex imaging approaches. Patients were followed prospectively (median 3 years) and classified into four recurrence groups; early (<6 months after resection) or late (>6 months after resection) liver metastasis (LiM); extrahepatic metastasis (EHM); and disease-free survivors (no evidence of disease (NED)). Overall, PaC livers exhibited signs of augmented inflammation compared to controls. Enrichment of neutrophil extracellular traps (NETs), Ki-67 upregulation and decreased liver creatine significantly distinguished those with future metastasis from NED. Patients with future LiM were characterized by scant T cell lobular infiltration, less steatosis and higher levels of citrullinated H3 compared to patients who developed EHM, who had overexpression of interferon target genes (MX1 and NR1D1) and an increase of CD11B+ natural killer (NK) cells. Upregulation of sortilin-1 and prominent NETs, together with the lack of T cells and a reduction in CD11B+ NK cells, differentiated patients with early-onset LiM from those with late-onset LiM. Liver profiles of NED closely resembled those of controls. Using the above parameters, a machine-learning-based model was developed that successfully predicted the metastatic outcome at the time of surgery with 78% accuracy. Therefore, multi-parametric profiling of liver biopsies at the time of PaC diagnosis may determine metastatic risk and organotropism and guide clinical stratification for optimal treatment selection.


Assuntos
Neoplasias Hepáticas , Fígado , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirurgia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fígado/patologia , Fígado/metabolismo , Biópsia , Estadiamento de Neoplasias , Pancreatectomia , Armadilhas Extracelulares/metabolismo , Prognóstico
12.
Children (Basel) ; 11(6)2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38929312

RESUMO

BACKGROUND: Pediatric regional anesthesia has been driven by the gradual rise in the adoption of opioid-sparing strategies and the growing concern over the possible adverse effects of general anesthetics on neurodevelopment. Nonetheless, performing regional anesthesia studies in a pediatric population is challenging and accounts for the scarce evidence. This study aimed to review the scientific foundation of studies in cadavers to assess regional anesthesia techniques in children. METHODS: We searched the following databases MEDLINE, EMBASE, and Web of Science. We included anatomical cadaver studies assessing peripheral nerve blocks in children. The core data collected from studies were included in tables and comprised block type, block evaluation, results, and conclusion. RESULTS: The search identified 2409 studies, of which, 16 were anatomical studies on the pediatric population. The techniques evaluated were the erector spinae plane block, ilioinguinal/iliohypogastric nerve block, sciatic nerve block, maxillary nerve block, paravertebral block, femoral nerve block, radial nerve block, greater occipital nerve block, infraclavicular brachial plexus block, and infraorbital nerve block. CONCLUSION: Regional anesthesia techniques are commonly performed in children, but the lack of anatomical studies may result in reservations regarding the dispersion and absorption of local anesthetics. Further anatomical research on pediatric regional anesthesia may guide the practice.

13.
Nutrients ; 16(12)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38931197

RESUMO

(1) Background: Dysregulated serum amino acids (AA) are known to be associated with obesity and risk of Type 2 Diabetes (T2D) in adults, and recent studies support the same notion in the pubertal age. It is, however, unknown whether childhood overweight may already display alterations of circulating AA. (2) Methods: We used liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS)-targeted metabolomics to determine plasma concentrations of AA and AA-related molecules in 36 children aged 7-12 years with normal weight or overweight. Clinical and anthropometric parameters were measured. (3) Results: Overweight in children is associated with an altered AA profile, with increased branched-chain amino acids (BCAA) and decreased glycine levels, with no clinically manifested metabolic conditions. Moreover, z-BMI was positively and negatively correlated with BCAA and glycine levels, respectively, even after adjustment for age and gender. We also found a correlation between the AA profile and clinical parameters such as lipids profile and glycemia. (4) Conclusions: A pattern of low glycine, and increased BCAA is correlated to z-BMI, total cholesterol, and triglycerides in overweight but otherwise healthy children. Our data suggest that, in childhood overweight, AA disturbances may precede other clinical parameters, thus providing an early indicator for the later development of metabolic disease.


Assuntos
Aminoácidos de Cadeia Ramificada , Aminoácidos , Glicina , Sobrepeso , Obesidade Infantil , Humanos , Criança , Feminino , Masculino , Glicina/sangue , Aminoácidos de Cadeia Ramificada/sangue , Aminoácidos/sangue , Sobrepeso/sangue , Obesidade Infantil/sangue , Índice de Massa Corporal , Espectrometria de Massas em Tandem , Cromatografia Líquida , Metabolômica/métodos , Triglicerídeos/sangue
14.
Vet Res Commun ; 48(4): 2819-2826, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38822954

RESUMO

In August 2021, two juvenile male Antarctic fur seals (Arctocephalus gazella) stranded in the southeastern Brazilian coast and were referred to rehabilitation centers. The animals presented increased body temperature, prostration, respiratory distress and despite treatment died. A necropsy following a standardized protocol was performed, and formalin-fixed tissues were processed for microscopic examination. Samples were screened for morbillivirus, herpesvirus, and Brucella spp. by molecular analyses (PCR, RT-PCR). Bacteriological culture was performed in samples collected from the lungs, trachea, and lymph nodes of both cases. The main histopathologic findings were of infectious nature, including multifocal necrotizing and fibrinous mixed interstitial pneumonia, bronchiolitis, and bronchitis, with intralesional myriad bacteria associated with vascular fibrinoid necrosis. Pseudomonas aeruginosa was isolated from tracheal and lung swabs of Case 1, and Klebsiella oxytoca was found in nostril swabs, tracheobronchial lymph nodes, and lung of Case 2. Gammaherpesvirus infection was detected in both cases, and the sequences retrieved were classified into the genus Percavirus. All tested samples were PCR-negative for Brucella spp. and morbillivirus. We hypothesize that the deficient immunological status in association with starvation predisposed the reactivation of herpesvirus and secondary bacterial co-infections. To the authors' knowledge, this is the first molecular detection of herpesvirus in an Antarctic pinniped. These findings reinforce that Otariid gammaherpesvirus circulating in the Southern Hemisphere are likely endemic in the Arctocephalus genus. This report contributes to the current knowledge of health aspects affecting wild pinnipeds, especially in the poorly studied Antarctic species.


Assuntos
Otárias , Infecções por Herpesviridae , Animais , Brasil , Otárias/virologia , Infecções por Herpesviridae/veterinária , Infecções por Herpesviridae/virologia , Masculino , Sepse/veterinária , Sepse/microbiologia , Sepse/virologia
15.
Int J Mol Sci ; 25(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38892196

RESUMO

Acute lymphoblastic leukaemia is currently treated with bacterial L-asparaginase; however, its side effects raise the need for the development of improved and efficient novel enzymes. Previously, we obtained low anti-asparaginase antibody production and high serum enzyme half-life in mice treated with the P40S/S206C mutant; however, its specific activity was significantly reduced. Thus, our aim was to test single mutants, S206C and P40S, through in vitro and in vivo assays. Our results showed that the drop in specific activity was caused by P40S substitution. In addition, our single mutants were highly stable in biological environment simulation, unlike the double-mutant P40S/S206C. The in vitro cell viability assay demonstrated that mutant enzymes have a higher cytotoxic effect than WT on T-cell-derived ALL and on some solid cancer cell lines. The in vivo assays were performed in mice to identify toxicological effects, to evoke immunological responses and to study the enzymes' pharmacokinetics. From these tests, none of the enzymes was toxic; however, S206C elicited lower physiological changes and immune/allergenic responses. In relation to the pharmacokinetic profile, S206C exhibited twofold higher activity than WT and P40S two hours after injection. In conclusion, we present bioengineered E. coli asparaginases with high specific enzyme activity and fewer side effects.


Assuntos
Asparaginase , Escherichia coli , Animais , Asparaginase/genética , Asparaginase/metabolismo , Escherichia coli/genética , Camundongos , Humanos , Mutação , Linhagem Celular Tumoral , Feminino , Sobrevivência Celular/efeitos dos fármacos , Inflamação/genética
16.
BMC Cancer ; 24(1): 709, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38853244

RESUMO

BACKGROUND: Pancreatic cancer, predominantly characterized by ductal adenocarcinoma (PDAC) accounts for 90% of cases and is the fourth leading cause of cancer-related deaths globally. Its incidence is notably increasing. This poor prognosis is primarily due to late-stage diagnosis (approximately 70% to 80% of patients are diagnosed at an advanced stage), aggressive tumor biology, and low sensitivity to chemotherapy. Consequently, it is crucial to identify and develop a simple, feasible and reproducible blood-based signature (i.e., combination of biomarkers) for early detection of PDAC. METHODS: The PANLIPSY study is a multi-center, non-interventional prospective clinical trial designed to achieve early detection of PDAC with high specificity and sensitivity, using a combinatorial approach in blood samples. These samples are collected from patients with resectable, borderline or locally advanced, and metastatic stage PDAC within the framework of the French Biological and Clinical Database for PDAC cohort (BACAP 2). All partners of the BACAP consortium are eligible to participate. The study will include 215 PDAC patients, plus 25 patients with benign pancreatic conditions from the PAncreatic Disease Cohort of TOuLouse (PACTOL) cohort, and 115 healthy controls, totaling 355 individuals. Circulating biomarkers will be collected in a total volume of 50 mL of blood, divided into one CellSave tube (10 mL), two CELL-FREE DNA BCT® preservative tubes (18 mL), and five EDTA tubes (22 mL in total). Samples preparation will adhere to the guidelines of the European Liquid Biopsy Society (ELBS). A unique feature of the study is the AI-based comparison of these complementary liquid biopsy biomarkers. Main end-points: i) to define a liquid biopsy signature that includes the most relevant circulating biomarkers, ii) to validate the multi-marker panel in an independent cohort of healthy controls and patients, with resectable PDAC, and iii) to establish a unique liquid biopsy biobank for PDAC study. DISCUSSION: The PANLIPSY study is a unique prospective non-interventional clinical trial that brings together liquid biopsy experts. The aim is to develop a biological signature for the early detection of PDAC based on AI-assisted detection of circulating biomarkers in blood samples (CTCs, ctDNA, EVs, circulating immune system, circulating cell-free nucleosomes, proteins, and microbiota). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06128343 / NCT05824403. Registration dates: June 8,2023 and April 21, 2023.


Assuntos
Biomarcadores Tumorais , Carcinoma Ductal Pancreático , Detecção Precoce de Câncer , Neoplasias Pancreáticas , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patologia , Detecção Precoce de Câncer/métodos , França , Biópsia Líquida/métodos , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Estudos Prospectivos
17.
Int J Psychol ; 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38852955

RESUMO

This research investigates discrimination against suspected Islamic terrorists based on tolerance for the use of torture. This research is justified by the need to identify how intergroup and ideological factors combine to express discrimination. Two experimental studies were conducted with a between-subjects design. Study 1 (N = 282) analysed the terrorist threat against the ingroup and the nationality of torturers with respect to support for torture against suspected Islamic terrorists. Study 2 (N = 165) analysed the interaction among terrorist threat against the ingroup and perceived threat (realistic and symbolic) as moderators in the relationship between RWA and discrimination. Study 1 indicated that support for torture was greater when the victims of terrorist acts and the torturers belonged to the ingroup. Study 2 indicated that the perceived threat encourages support for the use of torture, regardless of the levels of RWA. Taken together, these results elucidate the psychosocial processes that are present in the hostility towards social minorities from predominantly Muslim countries and in the strengthening of xenophobic political positions.

18.
Transplant Direct ; 10(6): e1643, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38769976

RESUMO

Background: The urinary microbiome, also known as the urobiome, was traditionally considered sterile. However, emerging evidence suggests its presence in the urinary tract. Urobiome dysbiosis has been associated with various urologic conditions, making it a topic of interest also in kidney transplantation. This systematic review examines the evidence of urobiome changes in kidney transplant recipients (KTRs). Methods: Systematic literature searches in the PubMed and SCOPUS databases. Results: Of the 770 articles identified, 8 met the inclusion criteria. The urobiome showed reduced diversity in KTRs compared with healthy controls and patients on dialysis. Proteobacteria enrichment was associated with graft stability or spontaneous tolerance in KTRs without immunological events. Kidney interstitial fibrosis and tubular atrophy were associated with changes in resident urinary microbes and increased pathogenic bacteria. Additionally, KTRs with chronic allograft dysfunction had a higher prevalence of Corynebacterium. Conclusions: The review highlights the importance of studying the urobiome in KTRs and its potential impact on transplant outcomes. The field remains largely unexplored, and further research is needed to establish consistent study designs and objectives. Future studies could lead to biomarker discovery, personalized therapies, and improved outcomes and graft survival in KTRs.

19.
Motor Control ; 28(3): 276-304, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38580301

RESUMO

Premature life exposure, meaning an immature central nervous system, presents a significant challenge for the development of postural control and, in turn, overall motor development. Preventing motor delay thus requires identifying, characterizing, and quantifying deficit in postural control as early as possible. In our study, we reviewed the procedures used in past studies to assess postural control among individuals born preterm, specifically the characterization of participants, the instruments and motor tasks involved, the types of data collected and analyzed, and the outcomes. To that end, we performed a literature search on PubMed, Wiley Online Library, Web of Science, and Scopus using Boolean logic and assessed the quality of the studies with a standardized assessment based on the Strengthening the Reporting of Observational Studies in Epidemiology guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. Of 35 potential studies, 24 were included; all evaluated infants born preterm, but six did not include a control group of full-term infants. Although the heterogeneity of measurements, variability of instruments, and divergence in motor tasks examined limit definitive conclusions based on quantitative synthesis and the generalization of the results, most studies revealed dysfunctional postural control among individuals born preterm.


Assuntos
Recém-Nascido Prematuro , Equilíbrio Postural , Humanos , Equilíbrio Postural/fisiologia , Recém-Nascido Prematuro/fisiologia , Recém-Nascido , Lactente , Criança , Adulto
20.
Artigo em Inglês | MEDLINE | ID: mdl-38688175

RESUMO

The present work aimed at the development and characterization of aroeira leaf flour (Schinus terebinthifolius Raddi), obtained by lyophilization and drying in an air circulation oven. The technological, physical, physico-chemical, morphological, functional, and microbiological aspects were analyzed. Physico-chemical analysis identified the following properties with values provided respectively for fresh leaves (FOin) and flours (FES and FLIO): low water activity (0.984, 0.370, 0.387 g/100 g), moisture (64.52, 5.37, 7.97 g /100 g), ash (2.69, 6.51, and 6.89 g/100 g), pH (0.89, 4.45, 4.48 g/100 g), lipids (0.84, 1.67, 5.23 g/100 g), protein (3.29, 8.23, 14.12 g/100 g), carbohydrates (17.02, 53.12, 33.02 g/100 g), ascorbic acid (19.70, 34.20, 36.90 mg/100 g). Sources of fiber from plant leaves and flours (11.64, 25.1, 32.89 g/100 g) showed increased levels of luminosity. For NMR, the presence of aliphatic and aromatic compounds with olefinic hydrogens and a derivative of gallic acid were detected. The most abundant minerals detected were potassium and calcium. Micrographs identified the presence of irregular, non-uniform, and sponge-like particles. The main sugars detected were: fructose, glucose, and maltose. Malic, succinic, citric, lactic, and formic acids were found. Fifteen phenolic compounds were identified in the samples, highlighting: kaempferol, catechin, and caffeic acid. The values ​​found for phenolics were (447, 716.66, 493.31 mg EAG/100 g), flavonoids (267.60, 267.60, 286.26 EC/100 g). Antioxidant activity was higher using the ABTS method rather than FRAP for analysis of FOin, FES, and FLIO. Since the flours of the aroeira leaf have an abundant matrix of nutrients with bioactive properties and antioxidant activity, they have a potential for technological and functional use when added to food.


Assuntos
Anacardiaceae , Farinha , Folhas de Planta , Folhas de Planta/química , Anacardiaceae/química , Farinha/análise , Liofilização , Carboidratos/análise , Carboidratos/química , Antioxidantes/análise , Antioxidantes/química , Schinus
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