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1.
Allergol Immunopathol (Madr) ; 52(4): 68-72, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38970267

RESUMO

INTRODUCTION AND OBJECTIVES: Both asthma prevalence and the percentage of cesarean sections have increased in parallel in recent years. Research studies suggest an increased risk of developing atopic diseases and asthma after cesarean section birth compared to vaginal delivery. The main objective of this study is to analyze the risk of asthma admission after cesarean section birth compared to vaginal delivery in the pediatric population. POPULATION AND METHODS: Retrospective observational analytical case-control study from 1993 to 2020. The cases include all admitted patients to our health area hospital, for patients aged 7 to 16 diagnosed with asthma. For each case, a control without a diagnosis of asthma is selected with the same age, and that has also caused an episode of admission. RESULTS: A total of 290 admission episodes with a diagnosis of asthma were obtained, caused by 155 patients. Out of these, 145 cases with documented delivery types were selected. For cases, 155 controls were selected. The historical proportion of cesarean sections in the asthmatic group is 18.6%, compared to 14.2% in the non-asthmatic group. There is a statistically non-significant difference of 4.4% more cesarean sections in the asthmatic group compared to the control group. DISCUSSION: We have not demonstrated a statistically significant association between being born by cesarean section and an increased risk of asthma admission. Based on this finding, we cannot conclude that there is an association between being born by cesarean section and a higher risk of suffering from asthma, unlike what has been postulated in other research studies.


Assuntos
Asma , Cesárea , Humanos , Cesárea/estatística & dados numéricos , Cesárea/efeitos adversos , Asma/epidemiologia , Feminino , Estudos Retrospectivos , Criança , Estudos de Casos e Controles , Adolescente , Gravidez , Masculino , Fatores de Risco , Prevalência , Risco
2.
Sci Total Environ ; 946: 174277, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38944300

RESUMO

Microorganisms form dynamic communities with plants, providing benefits such as nutrient acquisition and stress resilience. Understanding how these microorganisms are affected by environmental factors such as growth conditions and soil characteristics are essential for harnessing these communities for sustainable agriculture practices and their response to climate change. The microbiome associated to Lupinus angustifolius, a legume native in Europe, with a high protein value and stress resilience was characterized for the first time. Using 16S rRNA gene and ITS amplicon sequencing, we characterized the compositional and temporal changes of the bacterial and fungal communities associated to the soil, rhizosphere, and plant compartments where Lupinus angustifolius grows naturally. Our results suggest that the main difference in the soil microbial communities is related to the edaphic properties, although environmental factors such as temperature, humidity or rainfall also influenced the composition of the soil microbial communities. We also characterized the bacterial communities associated with the rhizosphere, roots, nodules, and leaves of wild plants collected in the field and compared them against plants obtained under greenhouse conditions. In the plant compartments, the bacterial composition appeared to be more affected by the growing conditions (field vs greenhouse), than by soil characteristics or location. These results can be used to identify key taxa that may play crucial roles in the development and adaptation of the host plant and its associated microbiota to environmental changes and highlight the importance of characterizing the plant microbiomes in their natural habitats. Soil, influenced by climatic seasons, shapes the plant microbiome assembly. Lupinus recruits a core microbiome across rhizosphere, roots, nodules, and leaves, that is stable across locations. However, cultivation conditions may alter microbiome dynamics, impacting the adaptability of its components. Wild plants show a resilient and adaptable microbiome while germination and cultivation in greenhouse conditions alter its composition and vulnerability.

3.
Menopause ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916283

RESUMO

OBJECTIVE: This study aimed to ascertain the accuracy of measure arterial stiffness using the HUAWEI GT 3 Pro smartwatch and pOpmètre device against the SphygmoCor (algorithms: intersect tangent and maximum of the second derivate). METHODS: Twenty-three physically active postmenopausal women (age: 58.9 ± 3.2 years; body mass index: 26.3 ± 4.8 kg/m2) were recruited. Carotid-femoral pulse wave velocity, finger-toe pulse wave velocity, and wrist-finger pulse wave velocity were obtained using SphygmoCor, pOpmètre and HUAWEI GT 3 Pro devices in a randomized order. Additionally, the pulse mean carotid-femoral and finger-toe pulse transit time was registered for SphygmoCor and pOpmètre, respectively. RESULTS: Lower values of pulse wave velocity were recorded by HUAWEI in comparison with SphygmoCor with both algorithms, whereas no significant differences were detected between SphygmoCor and pOpmètre results. Pulse wave velocity values from SphygmoCor were positively correlated with pOpmètre results (r = 0.464 and r = 0.451 using intersect tangent and second derivative algorithms), whereas this was not the case with those obtained from HUAWEI. Coefficients of bias of Lin's concordance coefficients close to 1 (0.832 and 0.831 for intersect tangent and second derivative algorithm, respectively) and mean bias close to 0 from Bland-Altman analysis suggested an acceptable agreement between pulse wave velocity obtained from SphygmoCor and pOpmètre. CONCLUSIONS: Our results suggest an acceptable concordance of pulse wave velocity values recoded by SphygmoCor and pOpmètre, whereas this was not the case for data obtained from HUAWEI GT 3 Pro smartwatch. Therefore, the pOpmètre may be a viable alternative for assessing arterial stiffness, but measurement via the smartwatch device cannot be recommended.

4.
J Ethnopharmacol ; 333: 118500, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38944359

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: African wormwood (Artemisia afra Jacq. ex Willd.) has been used traditionally in southern Africa to treat illnesses causing fever and was recently shown to possess anti-tuberculosis activity. As tuberculosis is an endemic cause of fever in southern Africa, this suggests that the anti-tubercular activity of A. afra may have contributed to its traditional medicinal use. AIM OF THE STUDY: Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a deadly and debilitating disease globally affecting millions annually. Emerging drug-resistant Mtb strains endanger the efficacy of the current therapies employed to treat tuberculosis; therefore, there is an urgent need to develop novel drugs to combat this disease. Given the reported activity of A. afra against Mtb, we sought to determine the mechanisms by which A. afra inhibits and kills this bacterium. MATERIALS AND METHODS: We used transcriptomics to investigate the impact of Artemisia spp. extracts on Mtb physiology. We then used chromatographic fractionation and biochemometric analyses to identify a bioactive fractions of A. afra extracts and identify an active compound. RESULTS: Transcriptomic analysis revealed that A. afra exerts different effects on Mtb compared to A. annua or artemisinin, suggesting that A. afra possesses other phytochemicals with unique modes of action. A biochemometric study of A. afra resulted in the isolation of an O-methylflavone (1), 5-hydroxy-7-methoxy-2-(4-methoxyphenyl)chromen-4-one, which displayed considerable activity against Mtb strain mc26230 in both log phase growth and metabolically downshifted hypoxic cultures. CONCLUSIONS: The present study demonstrated that an O-methylflavone constituent of Artemisia afra explains part of the activity of this plant against Mtb. This result contributes to a mechanistic understanding of the reported anti-tubercular activity of A. afra and highlights the need for further study of this traditional medicinal plant and its active compounds.

5.
Vaccine ; 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38880691

RESUMO

Vaccination is the best strategy to control Paratuberculosis (PTB), which is a significant disease in cattle and sheep. Previously we showed the humoral and cellular immune response induced by a novel vaccine candidate against PTB based on the Argentinian Mycobacterium avium subspecies paratuberculosis (Map) 6611 strain. To improve 6611 immunogenicity and efficacy, we evaluated this vaccine candidate in mice with two different adjuvants and a heterologous boost with a recombinant modified vaccinia Ankara virus (MVA) expressing the antigen 85A (MVA85A). We observed that boosting with MVA85A did not improve total IgG or specific isotypes in serum induced by one or two doses of 6611 formulated with incomplete Freund's adjuvant (IFA). However, when 6611 was formulated with ISA201 adjuvant, MVA85A boost enhanced the production of IFNγ, Th1/Th17 cytokines (IL-2, TNF, IL-17A) and IL-6, IL-4 and IL-10. Also, this group showed the highest levels of IgG2b and IgG3 isotypes, both important for better protection against Map infection in the murine model. Finally, the heterologous scheme elicited the highest levels of protection after Map challenge (lowest CFU count and liver lesion score). In conclusion, our results encourage further evaluation of 6611 strain + ISA201 prime and MVA85A boost in bovines.

6.
Ther Adv Neurol Disord ; 17: 17562864241243274, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827243

RESUMO

Background: Cerebral small vessel disease is the most common cause of lacunar strokes (LS). Understanding LS pathogenesis is vital for predicting disease severity, prognosis, and developing therapies. Objectives: To research molecular profiles that differentiate LS in deep brain structures from those in subcortical white matter. Design: Prospective case-control study involving 120 patients with imaging-confirmed LS and a 120 control group. Methods: We examined the relationship between Alzheimer's disease biomarkers [amyloid beta (Aß1-40, Aß1-42)], serum inflammatory marker (interleukin-6, IL-6), and endothelial dysfunction markers [soluble tumor necrosis factor-like weak inducer of apoptosis, and pentraxin-3 (sTWEAK, PTX3)] with respect to LS occurring in deep brain structures and subcortical white matter. In addition, we investigated links between LS, leukoaraiosis presence (white matter hyperintensities, WMHs), and functional outcomes at 3 months. Poor outcome was defined as a modified Rankin scale >2 at 3 months. Results: Significant differences were observed in levels of IL-6, PTX3, and sTWEAK between patients with deep lacunar infarcts and those with recent small subcortical infarcts (20.8 versus 15.6 pg/mL, p < 0.001; 7221.3 versus 4624.4 pg/mL, p < 0.0001; 2528.5 versus 1660.5 pg/mL, p = 0.001). Patients with poor outcomes at 3 months displayed notably higher concentrations of these biomarkers compared to those with good outcomes. By contrast, Aß1-40 and Aß1-42 were significantly lower in patients with deep LS (p < 0.0001). Aß1-42 levels were significantly higher in patients with LS in subcortical white matter who had poor outcomes. WMH severity only showed a significant association with deep LS and correlated with sTWEAK (p < 0.0001). Conclusion: The pathophysiological mechanisms of lacunar infarcts in deep brain structures seem different from those in the subcortical white matter. As a result, specific therapeutic and preventive strategies should be explored.

7.
Curr Protoc ; 4(6): e1060, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38923371

RESUMO

The endoplasmic reticulum (ER) is the main reservoir of Ca2+ of the cell. Accurate and quantitative measuring of Ca2+ dynamics within the lumen of the ER has been challenging. In the last decade a few genetically encoded Ca2+ indicators have been developed, including a family of fluorescent Ca2+ indicators, dubbed GFP-Aequorin Proteins (GAPs). They are based on the fusion of two jellyfish proteins, the green fluorescent protein (GFP) and the Ca2+-binding protein aequorin. GAP Ca2+ indicators exhibit a combination of several features: they are excitation ratiometric indicators, with reciprocal changes in the fluorescence excited at 405 and 470 nm, which is advantageous for imaging experiments; they exhibit a Hill coefficient of 1, which facilitates the calibration of the fluorescent signal into Ca2+ concentrations; they are insensible to variations in the Mg2+ concentrations or pH variations (in the 6.5-8.5 range); and, due to the lack of mammalian homologues, these proteins have a favorable expression in transgenic animals. A low Ca2+ affinity version of GAP, GAP3 (KD ≅ 489 µM), has been engineered to conform with the estimated [Ca2+] in the ER. GAP3 targeted to the lumen of the ER (erGAP3) can be utilized for imaging intraluminal Ca2+. The ratiometric measurements provide a quantitative method to assess accurate [Ca2+]ER, both dynamically and at rest. In addition, erGAP3 can be combined with synthetic cytosolic Ca2+ indicators to simultaneously monitor ER and cytosolic Ca2+. Here, we provide detailed methods to assess erGAP3 expression and to perform Ca2+ imaging, either restricted to the ER lumen, or simultaneously in the ER and the cytosol. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Detection of erGAP3 in the ER by immunofluorescence Basic Protocol 2: Monitoring ER Ca2+ Basic Protocol 3: Monitoring ER- and cytosolic-Ca2+ Support Protocol: Generation of a stable cell line expressing erGAP3.


Assuntos
Cálcio , Retículo Endoplasmático , Corantes Fluorescentes , Proteínas de Fluorescência Verde , Retículo Endoplasmático/metabolismo , Cálcio/metabolismo , Cálcio/análise , Proteínas de Fluorescência Verde/metabolismo , Proteínas de Fluorescência Verde/genética , Corantes Fluorescentes/química , Humanos , Equorina/metabolismo , Equorina/genética , Animais
8.
Burns ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38902134

RESUMO

BACKGROUND: In the days following a burn injury, major burn patients (MBP) present a multifactorial coagulation disorder known as acute burn-induced coagulopathy. Several studies have investigated coagulation in MBPs; however, Factor XIII (FXIII), which converts fibrin monomers into a stable clot and promotes wound healing, has not yet been studied. OBJECTIVE: To determine the kinetics of FXIII and other coagulation factors and cofactors in MBPs in order to clarify coagulopathy in these patients and its potential relationship with surgical bleeding. METHODS: Prospective observational pilot study of the kinetics of FXIII and other coagulation factors and cofactors in MBPs during the first 30 days of burn injury. RESULTS: FXIII levels show a significant decline of 75.10% in the interval between the burn injury and surgery, and a decline of 87.70% in the 24 h following surgery. Patients undergo surgery with a median antigenic FXIII of 32%. Plasma levels of most factors decrease significantly 24 h after the burn injury. CONCLUSION: MBPs experience a significant decrease in plasma levels of FXIII from the time of admission up to 24 h after surgery. Abnormally low levels were observed at the time of surgery that could not be detected by other coagulation tests. The decrease in most factors at 24 h seems to be associated with dilution due to intensive fluid resuscitation.

9.
BMC Health Serv Res ; 24(1): 745, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890678

RESUMO

INTRODUCTION: Medical First Responders (MFRs) in the emergency department SUMMA 112 are tasked with handling the initial management of Mass Casualty Incidents (MCI) and building response capabilities. Training plays a crucial role in preparing these responders for effective disaster management. Yet, evaluating the impact of such training poses challenges since true competency can only be proven amid a major event. As a substitute gauge for training effectiveness, self-efficacy has been suggested. OBJECTIVE: The purpose of this study is to employ a pre- and post-test assessment of changes in perceived self-efficacy among MFRs following an intervention focused on the initial management of MCI. It also aimed to evaluate a self-efficacy instrument for its validity and reliability in this type of training. METHOD: In this study, we used a pretest (time 1 = T1) - post-test (time 2 = T2) design to evaluate how self-efficacy changed after a training intervention with 201 MFRs in initial MCI management. ANOVA within-subjects and between subjects analyses were used. RESULTS: The findings reveal a noteworthy change in self-efficacy before and after training among the 201 participants. This suggests that the training intervention positively affected participants' perceived capabilities to handle complex situations like MCI. CONCLUSION: The results allow us to recommend a training program with theory components together with practical workshops and live, large-scale simulation exercises for the training of medical first responders in MCI, as it significantly increases their perception of the level of self-efficacy for developing competencies associated with disaster response.


Assuntos
Socorristas , Incidentes com Feridos em Massa , Autoeficácia , Humanos , Masculino , Feminino , Socorristas/psicologia , Socorristas/educação , Adulto , Planejamento em Desastres , Pessoa de Meia-Idade , Inquéritos e Questionários
10.
Int J Mol Sci ; 25(12)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38928260

RESUMO

Glutamate grabbers, such as glutamate oxaloacetate transaminase (GOT), have been proposed to prevent excitotoxicity secondary to high glutamate levels in stroke patients. However, the efficacy of blood glutamate grabbing by GOT could be dependent on the extent and severity of the disruption of the blood-brain barrier (BBB). Our purpose was to analyze the relationship between GOT and glutamate concentration with the patient's functional status differentially according to BBB serum markers (soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and leukoaraiosis based on neuroimaging). This retrospective observational study includes 906 ischemic stroke patients. We studied the presence of leukoaraiosis and the serum levels of glutamate, GOT, and sTWEAK in blood samples. Functional outcome was assessed using the modified Rankin Scale (mRS) at 3 months. A significant negative correlation between GOT and glutamate levels at admission was shown in those patients with sTWEAK levels > 2900 pg/mL (Pearson's correlation coefficient: -0.249; p < 0.0001). This correlation was also observed in patients with and without leukoaraiosis (Pearson's correlation coefficients: -0.299; p < 0.001 vs. -0.116; p = 0.024). The logistic regression model confirmed the association of higher levels of GOT with lower odds of poor outcome at 3 months when sTWEAK levels were >2900 pg/mL (OR: 0.41; CI 95%: 0.28-0.68; p < 0.0001) or with leukoaraiosis (OR: 0.75; CI 95%: 0.69-0.82; p < 0.0001). GOT levels are associated with glutamate levels and functional outcomes at 3 months, but only in those patients with leukoaraiosis and elevated sTWEAK levels. Consequently, therapies targeting glutamate grabbing might be more effective in patients with BBB dysfunction.


Assuntos
Ácido Glutâmico , AVC Isquêmico , Humanos , Ácido Glutâmico/sangue , Feminino , Masculino , Idoso , AVC Isquêmico/sangue , Pessoa de Meia-Idade , Estudos Retrospectivos , Medicina de Precisão/métodos , Biomarcadores/sangue , Aspartato Aminotransferases/sangue , Leucoaraiose/sangue , Barreira Hematoencefálica/metabolismo , Citocina TWEAK/sangue , Idoso de 80 Anos ou mais , Isquemia Encefálica/sangue
12.
J Control Release ; 372: 295-303, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38909703

RESUMO

Lipid nanoparticles (LNPs) currently dominate the RNA delivery landscape; however their limited diffusivity hampers targeted tissue dissemination, and, hence, their capacity for intracellular drug delivery. This is especially relevant for tissues such as the central nervous system (CNS), where overcoming proactive brain barriers is crucial for the efficacy of genetic therapeutics. This research aimed to create ionizable nanoemulsions (iNEs), a new generation of RNA delivery systems with enhanced diffusivity. The developed iNEs (consisting of the combination of C12-200, DOPE, Vitamin E, and DMG-PEG) with a size below 100 nm, neutral surface charge, and high RNA loading capacity, showed excellent cell viability and transfection efficiency in various cellular models, including neurons, astrocytes, and microglia. Subsequently, iNEs containing mRNA GFP were tested for CNS transfection, highlighting their exceptional diffusivity and selective transfection of neurons following intra-parenchymal administration.

13.
Drug Deliv Transl Res ; 14(8): 2026-2031, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38796665

RESUMO

This note aims to inspire through providing a personal view of the development and potential Drug Delivery Nanocarriers functionalized with polythyleneglycol (PEG). This polymer has been used extensively in Pharmaceutical Technology in a variety of compositions, including polyethylene oxide (PEO)-based surfactants. However, the concept of PEGylation, which started in the 70's, differs from the functionality of a surfactant, already discloses in the 50's. Here, we strictly adhere to the biological functionality of PEGylated nanocarriers intended to have a reduced interaction with proteins and, therefore, modify their biodistribution as well as facilitate their diffusion across mucus and other biological barriers. We analyze how this concept has evolved over the years and the benefit obtained so far in terms of marketed nanomedicines and provide the readers with a prospect view of the topic.


Assuntos
Portadores de Fármacos , Nanopartículas , Polietilenoglicóis , Animais , Humanos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Polietilenoglicóis/química , Polietilenoglicóis/administração & dosagem
14.
Drug Deliv Transl Res ; 14(8): 2046-2061, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38811465

RESUMO

The global emergency of coronavirus disease 2019 (COVID-19) has spurred extensive worldwide efforts to develop vaccines for protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our contribution to this global endeavor involved the development of a diverse library of nanocarriers, as alternatives to lipid nanoparticles (LNPs), including nanoemulsions (NEs) and nanocapsules (NCs), with the aim of protecting and delivering messenger ribonucleic acid (mRNA) for nasal vaccination purposes. A wide range of prototypes underwent rigorous screening through a series of in vitro and in vivo experiments, encompassing assessments of cellular transfection, cytotoxicity, and intramuscular administration of a model mRNA for protein translation. As a result, two promising candidates were identified for nasal administration. One of them was a NE incorporating a combination of an ionizable lipid (C12-200) and cationic lipid (DOTAP), both intended to condense mRNA, along with DOPE, which is known to facilitate endosomal escape. This NE exhibited a size of 120 nm and a highly positive surface charge (+ 50 mV). Another candidate was an NC formulation comprising the same components and endowed with a dextran sulfate shell. This formulation showed a size of 130 nm and a moderate negative surface charge (-16 mV). Upon intranasal administration of mRNA encoding for ovalbumin (mOVA) associated with optimized versions of the said NE and NCs, a robust antigen-specific CD8 + T cell response was observed. These findings underscore the potential of NEs and polymeric NCs in advancing mRNA vaccine development for combating infectious diseases.


Assuntos
Administração Intranasal , Vacinas contra COVID-19 , Emulsões , Nanocápsulas , Vacinas de mRNA , Nanocápsulas/química , Animais , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Camundongos , COVID-19/prevenção & controle , Nanopartículas/administração & dosagem , Nanopartículas/química , Humanos , SARS-CoV-2/imunologia , Feminino , Compostos de Amônio Quaternário/química , Camundongos Endogâmicos BALB C , Ácidos Graxos Monoinsaturados/química , RNA Mensageiro/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/administração & dosagem
15.
Artigo em Inglês | MEDLINE | ID: mdl-38821407

RESUMO

AIM: Myocardial uptake on bone scintigraphy has become useful for the detection of transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to assess the prevalence of myocardial uptake in patients over 18 years of age with no clinical suspicion of cardiac amyloidosis (CA) who had undergone bone scintigraphy. METHODS AND RESULTS: This was an observational, retrospective, multicenter study across 21 Spanish hospitals (September-November 2019). Of the 9864 scans analyzed (locally and centrally), incidental cardiac uptake was observed in 71 patients (0.72%), a prevalence that increased with age. A previous diagnosis of heart failure was found in 16.9% of patients with positive uptake, with >50% in NYHA II. ATTR-CA was diagnosed in 10 patients, with a mean delay of 10.4 months (95% CI: 5.1-15.7). All were >70 years old, primarily male, and had greater left ventricular hypertrophy than patients without a confirmed diagnosis (p<0.0001). ATTR-CA patients had higher rates of orthostatic hypotension (30.0% vs. 3.8% in non-ATTR-CA; p=0.025). CONCLUSIONS: This is the first retrospective, national, multicenter study evaluating the prevalence of incidental cardiac uptake in bone scintigraphy performed for non-cardiac reasons, showing a prevalence of 0.72% in this population. Referral of these patients may facilitate early diagnosis of CA with a resulting benefit for patients.

16.
iScience ; 27(5): 109787, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38711453

RESUMO

Depression is a devastating mood disorder that causes significant disability worldwide. Current knowledge of its pathophysiology remains modest and clear biological markers are lacking. Emerging evidence from human and animal models reveals persistent alterations in endoplasmic reticulum (ER) homeostasis, suggesting that ER stress-related signaling pathways may be targets for prevention and treatment. However, the neurobiological basis linking the pathways involved in depression-related ER stress remains unknown. Here, we report that an induced model of ER stress in mouse serotonin (5-HT) neurons is associated with reduced Egr1-dependent 5-HT cellular activity and 5-HT neurotransmission, resulting in neuroplasticity deficits in forebrain regions and a depressive-like phenotype. Ketamine administration engages downstream eIF2α signaling to trigger rapid neuroplasticity events that rescue the depressive-like effects. Collectively, these data identify ER stress in 5-HT neurons as a cellular pathway involved in the pathophysiology of depression and show that eIF2α is critical in eliciting ketamine's fast antidepressant effects.

19.
J Biomed Mater Res A ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775427

RESUMO

In this work, a sequential covalent immobilization of graphene oxide (GO) and hyaluronic acid (HA) is performed to obtain a biocompatible wear-resistant nanocoating on the surface of the biomedical grade cobalt-chrome (CoCr) alloy. Nanocoated CoCr surfaces were characterized by Raman spectroscopy and electrochemical impedance spectroscopy (EIS) in 3 g/L HA electrolyte. Tribocorrosion tests of the nanocoated CoCr surfaces were carried out in a pin on flat tribometer. The biological response of covalently HA/GO biofunctionalized CoCr surfaces with and without wear-corrosion processes was studied through the analysis of the proteome of macrophages. Raman spectra revealed characteristic bands of GO and HA on the functionalized CoCr surfaces. The electrochemical response by EIS showed a stable and protective behavior over 23 days in the simulated biological environment. HA/GO covalently immobilized on CoCr alloy is able to protect the surface and reduce the wear volume released under tribocorrosion tests. Unsupervised classification analysis of the macrophage proteome via hierarchical clustering and principal component analysis (PCA) revealed that the covalent functionalization on CoCr enhances the macrophage biocompatibility in vitro. On the other hand, disruption of the HA/GO nanocoating by tribocorrosion processes induced a macrophage proteome which was differently clustered and was distantly located in the PCA space. In addition, tribocorrosion induced an increase in the percentage of upregulated and downregulated proteins in the macrophage proteome, revealing that disruption of the covalent nanocoating impacts the macrophage proteome. Although macrophage inflammation induced by tribocorrosion of HA/GO/CoCr surfaces is observed, it is ameliorated by the covalently grafting of HA, which provides immunomodulation by eliciting downregulations in characteristic pro-inflammatory signaling involved in inflammation and aseptic loosening of CoCr joint arthroplasties. Covalent HA/GO nanocoating on CoCr provides potential applications for in vivo joint prostheses led a reduced metal-induced inflammation and degradation by wear-corrosion.

20.
Materials (Basel) ; 17(10)2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38793354

RESUMO

The co-processing of different wastes as fuels in the manufacture of cement clinker not only meets the objectives of a circular economy but also contributes to the reduction in CO2 emissions in the manufacture of Portland cement. However, waste used as alternative fuels, such as sludge or organic-rich residues, may contain naturally occurring radionuclides that can be concentrated during the combustion process. In this study, the presence of natural radionuclides (radioactive series of uranium, thorium, and 40K) and anthropogenic radionuclides (137Cs) in these wastes has been investigated by gamma spectrometry. Possible relationships between the radioactive content and the obtained chemical composition, determined by X-ray fluorescence, have also been studied by applying a principal component analysis (PCA). The results showed that the wastes with the highest radioactive content were sewage sludge with activity concentrations of 238U and 210Pb of 321 ± 38 Bq kg-1 and 110 ± 14 Bq kg-1, respectively. A correlation between radioactive content and Fe2O3 concentration was also observed. The annual effective dose rates to workers for the ashes estimated from the ash content ranged from 0.0033 mSv to 0.092 mSv and therefore do not pose a risk to workers as they are lower than the 1 mSv per year limit for the general public (DIRECTIVE 2013/59/EURATOM).

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