Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 658
Filter
1.
Int J Mol Sci ; 25(12)2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38928411

ABSTRACT

This study aimed to investigate the gut microbiota composition in children with autism spectrum disorder (ASD) compared to neurotypical (NT) children, with a focus on identifying potential differences in gut bacteria between these groups. The microbiota was analyzed through the massive sequencing of region V3-V4 of the 16S RNA gene, utilizing DNA extracted from stool samples of participants. Our findings revealed no significant differences in the dominant bacterial phyla (Firmicutes, Bacteroidota, Actinobacteria, Proteobacteria, Verrucomicrobiota) between the ASD and NT groups. However, at the genus level, notable disparities were observed in the abundance of Blautia, Prevotella, Clostridium XI, and Clostridium XVIII, all of which have been previously associated with ASD. Furthermore, a sex-based analysis unveiled additional discrepancies in gut microbiota composition. Specifically, three genera (Megamonas, Oscilibacter, Acidaminococcus) exhibited variations between male and female groups in both ASD and NT cohorts. Particularly noteworthy was the exclusive presence of Megamonas in females with ASD. Analysis of predicted metabolic pathways suggested an enrichment of pathways related to amine and polyamine degradation, as well as amino acid degradation in the ASD group. Conversely, pathways implicated in carbohydrate biosynthesis, degradation, and fermentation were found to be underrepresented. Despite the limitations of our study, including a relatively small sample size (30 ASD and 31 NT children) and the utilization of predicted metabolic pathways derived from 16S RNA gene analysis rather than metagenome sequencing, our findings contribute to the growing body of evidence suggesting a potential association between gut microbiota composition and ASD. Future research endeavors should focus on validating these findings with larger sample sizes and exploring the functional significance of these microbial differences in ASD. Additionally, there is a critical need for further investigations to elucidate sex differences in gut microbiota composition and their potential implications for ASD pathology and treatment.


Subject(s)
Autism Spectrum Disorder , Gastrointestinal Microbiome , Humans , Gastrointestinal Microbiome/genetics , Autism Spectrum Disorder/microbiology , Autism Spectrum Disorder/metabolism , Female , Male , Child , RNA, Ribosomal, 16S/genetics , Bacteria/classification , Bacteria/genetics , Bacteria/metabolism , Bacteria/isolation & purification , Feces/microbiology , Child, Preschool , Sex Factors , Sex Characteristics , Metabolic Networks and Pathways
2.
Int J Biol Macromol ; 273(Pt 2): 133181, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38880447

ABSTRACT

Nosocomial infections or healthcare-associated infections, normally develops after the healthcare treatment in the hospital. Most of them are caused by infected medical devices. Plastics are the most common materials for manufacturing these devices because of their good processability, sterilization efficacy, ease of handling and harmlessness, however, it usually do not display antimicrobial properties. Here, in order to infer antimicrobial activity to poly(lactic acid), it was modified by maleation, followed by l-lysine grafting to its structure. The chemical modifications were confirmed by FTIR and 1H NMR analysis, indicating the success of the reactions. The antimicrobial activity was tested using Escherichia coli and Staphylococcus aureus and the results showed that the sample was capable of inhibiting about 99 % of the S. aureus growth by contact. The samples cytotoxicity was also tested using the L929 mouse cells and the results indicated no cytotoxic effect. These results indicated the sample antimicrobial potential, without affect the normal eukaryotic cells. In addition, the processability of the modified PLA (PLA-g-Lys) was improved without compromising its mechanical properties, as shown by thermal analysis and tensile tests. Thus, this novel PLA derivative can be seen as a promising material for future applications in the manufacturing of biomedical devices.


Subject(s)
Escherichia coli , Lysine , Polyesters , Staphylococcus aureus , Polyesters/chemistry , Polyesters/pharmacology , Lysine/chemistry , Staphylococcus aureus/drug effects , Mice , Animals , Escherichia coli/drug effects , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Cell Line
3.
Comput Methods Programs Biomed ; 254: 108271, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38878362

ABSTRACT

BACKGROUND AND OBJECTIVE: Coronary plaque rupture is a precipitating event responsible for two thirds of myocardial infarctions. Currently, the risk of plaque rupture is computed based on demographic, clinical, and image-based adverse features. However, using these features the absolute event rate per single higher-risk lesion remains low. This work studies the power of a novel framework based on biomechanical markers accounting for material uncertainty to stratify vulnerable and non-vulnerable coronary plaques. METHODS: Virtual histology intravascular ultrasounds from 55 patients, 29 affected by acute coronary syndrome and 26 affected by stable angina pectoris, were included in this study. Two-dimensional vessel cross-sections for finite element modeling (10 sections per plaque) incorporating plaque structure (medial tissue, loose matrix, lipid core and calcification) were reconstructed. A Montecarlo finite element analysis was performed on each section to account for material variability on three biomechanical markers: peak plaque structural stress at diastolic and systolic pressure, and peak plaque stress difference between systolic and diastolic pressures, together with the luminal pressure. Machine learning decision tree classifiers were trained on 75% of the dataset and tested on the remaining 25% with a combination of feature selection techniques. Performance against classification trees based on geometric markers (i.e., luminal, external elastic membrane and plaque areas) was also performed. RESULTS: Our results indicate that the plaque structural stress outperforms the classification capacity of the combined geometric markers only (0.82 vs 0.51 area under curve) when accounting for uncertainty in material parameters. Furthermore, the results suggest that the combination of the peak plaque structural stress at diastolic and systolic pressures with the maximum plaque structural stress difference between systolic and diastolic pressures together with the systolic pressure and the diastolic to systolic pressure gradient is a robust classifier for coronary plaques when the intrinsic variability in material parameters is considered (area under curve equal to [0.91-0.93]). CONCLUSION: In summary, our results emphasize that peak plaque structural stress in combination with the patient's luminal pressure is a potential classifier of plaque vulnerability as it independently considers stress in all directions and incorporates total geometric and compositional features of atherosclerotic plaques.

4.
Mol Cell Neurosci ; 130: 103948, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38909878

ABSTRACT

Two sphingosine kinase isoforms, sphingosine kinase 1 (SPHK1) and sphingosine kinase 2 (SPHK2), synthesize the lipid sphingosine-1-phosphate (S1P) by phosphorylating sphingosine. SPHK1 is a cytoplasmic kinase, and SPHK2 is localized to the nucleus and other organelles. In the cytoplasm, the SPHK1/S1P pathway modulates autophagy and protein ubiquitination, among other processes. In the nucleus, the SPHK2/S1P pathway regulates transcription. Here, we hypothesized that the SPHK2/S1P pathway governs protein ubiquitination in neurons. We found that ectopic expression of SPHK2 increases ubiquitinated substrate levels in cultured neurons and pharmacologically inhibiting SPHK2 decreases protein ubiquitination. With mass spectrometry, we discovered that inhibiting SPHK2 affects lipid and synaptic protein networks as well as a ubiquitin-dependent protein network. Several ubiquitin-conjugating and hydrolyzing proteins, such as the E3 ubiquitin-protein ligases HUWE1 and TRIP12, the E2 ubiquitin-conjugating enzyme UBE2Z, and the ubiquitin-specific proteases USP15 and USP30, were downregulated by SPHK2 inhibition. Using RNA sequencing, we found that inhibiting SPHK2 altered lipid and neuron-specific gene networks, among others. Genes that encode the corresponding proteins from the ubiquitin-dependent protein network that we discovered with mass spectrometry were not affected by inhibiting SPHK2, indicating that the SPHK2/S1P pathway regulates ubiquitination at the protein level. We also show that both SPHK2 and HUWE1 were upregulated in the striatum of a mouse model of Huntington's disease, the BACHD mice, indicating that our findings are relevant to neurodegenerative diseases. Our results identify SPHK2/S1P as a novel regulator of protein ubiquitination networks in neurons and provide a new target for developing therapies for neurodegenerative diseases.

5.
Arch Pathol Lab Med ; 2024 May 27.
Article in English | MEDLINE | ID: mdl-38797525

ABSTRACT

CONTEXT.­: Interpretation of alkaline phosphatase (ALP) activity is essential for the diagnosis of certain diseases. ALP changes during life and may vary between different populations. OBJECTIVE.­: To establish reference intervals (RIs) and percentile charts for ALP activity in the Spanish population through a multicentric observational study and to compare the RIs to those defined in other countries. DESIGN.­: A total of 662 350 ALP measurements from individuals ages 0 to 99 years from 9 Spanish tertiary care centers collected between 2020 and 2022 were analyzed. This study is the largest published in the literature to date. RESULTS.­: Continuous percentile charts for ALP according to sex and age were established which can be used as RIs. Higher levels are reached during the first weeks of life. In puberty, a differential evolution is observed in both sexes, reaching a peak at 10 to 13 years of age in boys and remaining stable in girls at this age. Significant differences were also observed in adults, higher in men between ages 20 and 49 years and between ages 50 and 79 years in women, as reported in some countries. CONCLUSIONS.­: ALP activity follows an age- and sex-dependent fluctuation with geographic differences. It is important to have appropriate reference values for each population in order to allow for a correct diagnostic interpretation and early diagnosis of diseases related to ALP abnormalities.

6.
Biotech Histochem ; : 1-7, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38726944

ABSTRACT

Anterior cruciate ligament injuries are frequent afflictions related to sports or physical trauma. Autograft reconstruction strategies cause secondary injury to the patient. One alternative, supported by clinical evidence, is porcine xenografts. For clinical use, xenografts must be conditioned to avoid immune rejection. The most widely accepted procedure is tissue decellularization. We analyzed three decellularization strategies: the application of the anionic detergent sodium dodecyl sulfate (SDS), sonication, and freezing and thawing cycles. The treated tissues were evaluated histologically using H&E, Masson's trichrome, Verhoeff-van Gieson staining, and DAPI for fluorescent staining of nuclei. Finally, collagen fiber preservation was evaluated by quantifying this protein by colorimetry. The most efficient decellularization techniques were sonication and SDS. Collagen fibers were preserved in all experimental conditions.

7.
Int Orthop ; 48(8): 2137-2143, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38589709

ABSTRACT

PURPOSE: Third and fourth-generation minimal invasive osteotomies (MIO) for the treatment of hallux valgus (HV) have become popular procedures worldwide with promising results due to the improvement in the fixation method. The tricortical cannulated screw placement remains a complex procedure that is technically challenging and requires a long skill learning curve with high radiation exposure mainly in the form of intensifier shots (IS) required for the MIO fixation. This study aims to compare the number of X-ray IS required using three different techniques for the cannulated guide placement. METHODS: A retrospective cross-sectional observational and comparative study was conducted to assess the number of X-rays IS required for correct cannulated screw guide placement using three different techniques: traditional perforator, the drill and joystick, and K-wire first techniques. RESULTS: A total of 53 MIS procedures from thirty-one patients in two different hospitals were included. IS X-rays were 155.1 ± 29.7 in the traditional technique (n = 14), 143.0 ± 43.2 in the drill and joystick technique (n = 22), and 85 ± 18.7 in the K-wires first technique (n = 17), p = < 0.001 using one-way ANOVA. CONCLUSIONS: The K-wire first technique statistically significantly decreases X-ray IS numbers p ≤ 0.001. There were no statistically significant differences between the traditional (after osteotomy K-wire placement) and the drill and joystick techniques (p = 0.36).


Subject(s)
Bone Screws , Hallux Valgus , Minimally Invasive Surgical Procedures , Osteotomy , Humans , Hallux Valgus/surgery , Hallux Valgus/diagnostic imaging , Osteotomy/methods , Osteotomy/adverse effects , Osteotomy/instrumentation , Minimally Invasive Surgical Procedures/methods , Retrospective Studies , Cross-Sectional Studies , Female , Male , Middle Aged , Adult , Bone Wires , Aged , Radiography/methods , Treatment Outcome
8.
J Mech Behav Biomed Mater ; 152: 106413, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38281439

ABSTRACT

Keratoconus is a progressive ocular disorder affecting the corneal tissue, leading to irregular astigmatism and decreased visual acuity. The architectural organization of corneal tissue is altered in keratoconus, however, data from ex vivo testing of biomechanical properties of keratoconic corneas are limited and it is unclear how their results relate to true mechanical properties in vivo. This study explores the mechanical properties of keratoconic corneas through numerical simulations of non-contact tonometry (NCT) reproducing the clinical test of the Corvis ST device. Three sensitivity analyses were conducted to assess the impact of corneal material properties, size, and location of the pathological area on NCT results. Additionally, novel asymmetry-based indices were proposed to better characterize corneal deformations and improve the diagnosis of keratoconus. Our results show that the weakening of corneal material properties leads to increased deformation amplitude and altered biomechanical response. Furthermore, asymmetry indices offer valuable information for locating the pathological tissue. These findings suggest that adjusting the Corvis ST operation, such as a camera rotation, could enhance keratoconus detection and provide insights into the relative position of the affected area. Future research could explore the application of these indices in detecting early-stage keratoconus and assessing the fellow eye's risk for developing the pathology.


Subject(s)
Keratoconus , Humans , Keratoconus/diagnosis , Cornea , Tonometry, Ocular , Biomarkers , Manometry
9.
Biomech Model Mechanobiol ; 23(2): 525-537, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38063955

ABSTRACT

Transcatheter aortic valve implantation (TAVI) and thoracic endovascular aortic repair (TEVAR) are minimally invasive procedures for treating aortic valves and diseases. Finite element simulations have proven to be valuable tools in predicting device-related complications. In the literature, the inclusion of aortic pre-stress has not been widely investigated. It plays a crucial role in determining the biomechanical response of the vessel and the device-tissue interaction. This study aims at demonstrating how and when to include the aortic pre-stress in patient-specific TAVI and TEVAR simulations. A percutaneous aortic valve and a stent-graft were implanted in aortic models reconstructed from patient-specific CT scans. Two scenarios for each patient were compared, i.e., including and neglecting the wall pre-stress. The neglection of pre-stress underestimates the contact pressure of 48% and 55%, the aorta stresses of 162% and 157%, the aorta strains of 77% and 21% for TAVI and TEVAR models, respectively. The stent stresses are higher than 48% with the pre-stressed aorta in TAVI simulations; while, similar results are obtained in TEVAR cases. The distance between the device and the aorta is similar with and without pre-stress. The inclusion of the aortic wall pre-stress has the capability to give a better representation of the biomechanical behavior of the arterial tissues and the implanted device. It is suggested to include this effect in patient-specific simulations replicating the procedures.


Subject(s)
Aortic Aneurysm, Thoracic , Endovascular Procedures , Transcatheter Aortic Valve Replacement , Humans , Endovascular Procedures/methods , Aortic Valve/surgery , Stents , Aorta/surgery , Transcatheter Aortic Valve Replacement/methods , Treatment Outcome , Aorta, Thoracic/surgery , Blood Vessel Prosthesis
11.
Rev. bras. saúde ocup ; 49: edcinq17, 2024.
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1559632

ABSTRACT

Resumo Introdução: a política de atenção ao uso e abuso de álcool e outras drogas dos últimos anos demonstra suas limitações para responder às necessidades de atenção à saúde do(a) trabalhador(a) que usa essas substâncias para aliviar os efeitos adversos dos mecanismos hostis no contexto do trabalho. Objetivo: articular abordagens que reúnem um conjunto teórico-conceitual suficiente para abordar temas complexos e multicausais, como a relação entre o sofrimento psíquico e o trabalho, tendo como elemento principal o uso e abuso de álcool e outras drogas. Resultados: há evidências que apontam a relação entre mudanças no mercado de trabalho no contexto neoliberal, violência moral e ética no ambiente profissional e efeitos negativos sobre a saúde física-psíquica de trabalhadores. Evidenciou-se a necessidade de se romper com a lógica do funcionalismo subjetivista sobre o tema do uso e abuso de álcool e outras drogas relacionados ao trabalho. Conclusão: as estratégias políticas de atenção ao sofrimento psíquico decorrente do uso de álcool e outras drogas devem ir além das práticas focadas somente na abstinência e se basear na interface entre aportes teóricos integrativos, redução de danos e que considere a relação entre sofrimento e defesas dos sujeitos, o trabalho e o meio.


Abstract Introduction: policies aimed at use and abuse of alcohol and other drugs in recent years have shown their limitations in responding to the healthcare needs of workers who use and/or abuse alcohol and other drugs to alleviate the adverse effects from hostile work-related mechanisms. Objective: to articulate approaches that gather a theoretical-conceptual set that adequately addresses complex and multi-causal topics, such as the relation between psychological distress and work, with the use and abuse of alcohol and other drugs as their main element. Results: scientific evidence points out to the relation between neoliberal labor market changes, moral and ethical violence in the professional environment and negative effects on workers' physical and mental health. Studies argue about the need to break with the logic of subjectivist functionalism on the topic of work-related use and abuse of alcohol and other drugs. Conclusion: political strategies aimed at psychological suffering resulting from the use/abuse of alcohol and other drugs must go beyond practices solely focused on abstinence and include the interface between integrative theoretical contributions and harm reduction while considering the interaction between suffering and subjects' defenses, work and environment.

12.
Article in Portuguese | LILACS | ID: biblio-1551115

ABSTRACT

Este estudo objetivou estimar a prevalência do uso do cigarro eletrônico e a associação com fatores preditores. Trata-se de um estudo transversal, analítico, com amostra probabilística de universitários matriculados em um Centro Universitário de Montes Claros, Minas Gerais, Brasil no segundo semestre de 2022. A variável dependente referiu-se ao uso do cigarro eletrônico. As variáveis independentes referiram a fatores sociodemográficas, laborais e comportamentais. A associação entre as variáveis investigadas e a prevalência do uso do CE foi verificada pela análise bivariada e a regressão de Poisson. Foram entrevistados 730 universitários, com a média de idade de anos 22,56 (±6,25). Destes, 21,8 % faziam o uso cigarro eletrônico e após a análise multivariada manteve-se associado ao desfecho não ter companheiro (RP= 3,31; IC95% 1,04-10,48), morar com amigos/sozinho (RP=1,53; IC95% 1,07-2,18), ter histórico de usuários de cigarro eletrônico na residência (RP= 1,76; IC95%: 1,17- 1,89), consumir bebida alcoólica (RP= 3,07; IC95%: 1,72-5,49) e não praticar atividade física (RP= 3,37; IC95% 2,35-4,83). Conhecer sobre o cigarro eletrônico foi fator protetor (RP= 0,31 IC95% 0,20-0,46). Registrou-se elevada prevalência do uso do cigarro eletrônico, e manteve associados a fatores sociodemográficos e comportamentais. Esses achados chamam a atenção para a necessidade de novas medidas regulatórias, a fim de reduzir o uso desse dispositivo.


This study aimed to estimate the prevalence of e-cigarette use and the association with predictors. This is a cross-sectional, analytical study with a probabilistic sample of university students enrolled in a University Center of Montes Claros, Minas Gerais, Brazil in the second half of 2022. The dependent variable referred to the use of electronic cigarettes. The independent variables referred to sociodemographic, labor and behavioral factors. The association between the variables investigated and the prevalence of EC use was verified by bivariate analysis and Poisson regression. A total of 730 university students were interviewed, with a mean age of 22.56 (±6.25). Of these, 21.8% used electronic cigarettes and after multivariate analysis, it remained associated with the outcome of not having a partner (PR= 3.31; CI95% 1.04-10.48), living with friends/alone (PR=1.53; CI95% 1.07-2.18), having a history of e-cigarette users in the residence (PR= 1.76; CI95%: 1.17- 1.89), alcohol consumption (PR= 3.07; CI95%: 1.72-5.49) and not practicing physical activity (PR= 3.37; IC95% 2.35-4.83). Knowing about electronic cigarettes was a protective factor (PR= 0.31 CI95% 0.20-0.46). There was a high prevalence of e-cigarette use, and it was associated with sociodemographic and behavioral factors. These findings draw attention to the need for new regulatory measures in order to reduce the use of this device.


Este estudio tuvo como objetivo estimar la prevalencia del uso de cigarrillos electrónicos y la asociación con predictores. Se trata de un estudio analítico transversal con una muestra probabilística de estudiantes universitarios matriculados en un Centro Universitario de Montes Claros, Minas Gerais, Brasil, en el segundo semestre de 2022. La variable dependiente se refería al uso de cigarrillos electrónicos. Las variables independientes se refirieron a factores sociodemográficos, laborales y conductuales. La asociación entre las variables investigadas y la prevalencia de uso de CE fue verificada por análisis bivariado y regresión de Poisson. Fueron entrevistados 730 estudiantes universitarios, con una edad promedio de 22,56 (±6,25). De estos, 21,8% utilizaron cigarrillos electrónicos y después del análisis multivariado, se mantuvo asociado con el resultado de no tener pareja (RP= 3,31; IC95% 1,04-10,48), vivir con amigos/solo (RP=1,53; IC95% 1,07-2,18), con antecedentes de usuarios de cigarrillos electrónicos en la residencia (RP= 1,76; IC95%: 1,17- 1,89), consumo de alcohol (RP= 3,07; IC95%: 1,72-5,49) y no practicar actividad física (RP= 3,37; IC95% 2,35-4,83). El conocimiento de los cigarrillos electrónicos fue un factor protector (RP= 0,31 IC95% 0,20-0,46). Hubo una alta prevalencia de uso de cigarrillos electrónicos, y se asoció con factores sociodemográficos y de comportamiento. Estos hallazgos llaman la atención sobre la necesidad de nuevas medidas regulatorias para reducir el uso de este dispositivo.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Universities , Prevalence , Electronic Nicotine Delivery Systems/instrumentation , Behavior/physiology , Knowledge
13.
BMC Genomics ; 24(1): 696, 2023 Nov 20.
Article in English | MEDLINE | ID: mdl-37986038

ABSTRACT

BACKGROUND: Isabel Island is a Mexican volcanic island primarily composed of basaltic stones. It features a maar known as Laguna Fragatas, which is classified as a meromictic thalassohaline lake. The constant deposition of guano in this maar results in increased levels of phosphorus, nitrogen, and carbon. The aim of this study was to utilize high-quality genomes from the genus Halomonas found in specialized databases as a reference for genome mining of moderately halophilic bacteria isolated from Laguna Fragatas. This research involved genomic comparisons employing phylogenetic, pangenomic, and metabolic-inference approaches. RESULTS: The Halomonas genus exhibited a large open pangenome, but several genes associated with salt metabolism and homeostatic regulation (ectABC and betABC), nitrogen intake through nitrate and nitrite transporters (nasA, and narGI), and phosphorus uptake (pstABCS) were shared among the Halomonas isolates. CONCLUSIONS: The isolated bacteria demonstrate consistent adaptation to high salt concentrations, and their nitrogen and phosphorus uptake mechanisms are highly optimized. This optimization is expected in an extremophile environment characterized by minimal disturbances or abrupt seasonal variations. The primary significance of this study lies in the dearth of genomic information available for this saline and low-disturbance environment. This makes it important for ecosystem conservation and enabling an exploration of its biotechnological potential. Additionally, the study presents the first two draft genomes of H. janggokensis.


Subject(s)
Halomonas , Halomonas/genetics , Halomonas/metabolism , Lakes/microbiology , Phylogeny , Ecosystem , Genomics , Nitrogen/metabolism , Phosphorus/metabolism , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics
14.
J Neuroinflammation ; 20(1): 230, 2023 Oct 07.
Article in English | MEDLINE | ID: mdl-37805585

ABSTRACT

Stroke is the most common cause of long-term disability and places a high economic burden on the global healthcare system. Functional outcomes from stroke are largely determined by the extent of ischemic injury, however, there is growing recognition that systemic inflammatory responses also contribute to outcomes. Mast cells (MCs) rapidly respond to injury and release histamine (HA), a pro-inflammatory neurotransmitter that enhances inflammation. The gut serves as a major reservoir of HA. We hypothesized that cromolyn, a mast cell stabilizer that prevents the release of inflammatory mediators, would decrease peripheral and central inflammation, reduce MC trafficking to the brain, and improve stroke outcomes. We used the transient middle cerebral artery occlusion (MCAO) model of ischemic stroke in aged (18 mo) male mice to investigate the role of MC in neuroinflammation post-stroke. After MCAO we treated mice with 25 mg/kg body weight of cromolyn (MC stabilizer) by oral gavage. Cromolyn was administered at 3 h, 10 h, 24 h and every 24 h for 3 days post-stroke. Three control groups were used. One group underwent a sham surgery and was treated with cromolyn, one received sham surgery with PBS vehicle and the third underwent MCAO with PBS vehicle. Mice were euthanized at 24 h and 3 days post-stroke. Cromolyn administration significantly reduced MC numbers in the brain at both 24 h and 3 days post-stroke. Infarct volume was not significantly different between groups, however improved functional outcomes were seen at 3 days post-stroke in mice that received cromolyn. Treatment with cromolyn reduced plasma histamine and IL-6 levels in both the 24-h and 3-day cohorts. Gut MCs numbers were significantly reduced after cromolyn treatment at 24 h and 3 days after stroke. To determine if MC trafficking from the gut to the brain occurred after injury, GFP+MCs were adoptively transferred to c-kit-/- MC knock-out animals prior to MCAO. 24 h after stroke, elevated MC recruitment was seen in the ischemic brain. Preventing MC histamine release by cromolyn improved gut barrier integrity and an improvement in stroke-induced dysbiosis was seen with treatment. Our results show that preventing MC histamine release possesses prevents post-stroke neuroinflammation and improves neurological and functional outcomes.


Subject(s)
Histamine Release , Stroke , Humans , Mice , Male , Animals , Mast Cells , Cromolyn Sodium/pharmacology , Cromolyn Sodium/therapeutic use , Histamine , Neuroinflammatory Diseases , Stroke/complications , Inflammation/drug therapy , Inflammation/etiology , Infarction, Middle Cerebral Artery/complications , Infarction, Middle Cerebral Artery/drug therapy , Ischemia
16.
Aging Cell ; 22(11): e13977, 2023 11.
Article in English | MEDLINE | ID: mdl-37675802

ABSTRACT

Iron imbalance in the brain negatively affects brain function. With aging, iron levels increase in the brain and contribute to brain damage and neurological disorders. Changes in the cerebral vasculature with aging may enhance iron entry into the brain parenchyma, leading to iron overload and its deleterious consequences. Endothelial senescence has emerged as an important contributor to age-related changes in the cerebral vasculature. Evidence indicates that iron overload may induce senescence in cultured cell lines. Importantly, cells derived from female human and mice generally show enhanced senescence-associated phenotype, compared with males. Thus, we hypothesize that cerebral endothelial cells (CEC) derived from aged female mice are more susceptible to iron-induced senescence, compared with CEC from aged males. We found that aged female mice, but not males, showed cognitive deficits when chronically treated with ferric citrate (FC), and their brains and the brain vasculature showed senescence-associated phenotype. We also found that primary culture of CEC derived from aged female mice, but not male-derived CEC, exhibited senescence-associated phenotype when treated with FC. We identified that the transmembrane receptor Robo4 was downregulated in the brain vasculature and in cultured primary CEC derived from aged female mice, compared with those from male mice. We discovered that Robo4 downregulation contributed to enhanced vulnerability to FC-induced senescence. Thus, our study identifies Robo4 downregulation as a driver of senescence induced by iron overload in primary culture of CEC and a potential risk factor of brain vasculature impairment and brain dysfunction.


Subject(s)
Cellular Senescence , Iron Overload , Mice , Humans , Animals , Male , Female , Aged , Cellular Senescence/physiology , Endothelial Cells , Aging , Iron , Receptors, Cell Surface
17.
Sci Total Environ ; 903: 165984, 2023 Dec 10.
Article in English | MEDLINE | ID: mdl-37574072

ABSTRACT

Currently, discharge regulations for wastewater treatment plants (WWTPs) are based on conventional parameters, but more is needed to ensure safe water reuse. In particular, emerging pollutants, as antimicrobials and antibiotic resistance genes (ARGs), are not considered. This research focuses on the fate of emerging biological contaminants during wastewater treatment in Mexico City. intI1 and the ARGs cphA-02, OXA-10 and sul1 were analyzed by qPCR; pathogenic bacteria species were characterized by high throughput sequencing of complete 16S rRNA gene, and fragments of SARS-CoV-2 were quantified by RT-qPCR. Conventional parameters (chemical oxygen demand and coliform bacteria) were also determined. Two sampling campaigns (rainy and dry seasons) were carried out in four municipal WWTPs in Mexico City, representing five biological treatment processes: conventional activated sludge, extended aeration activated sludge, membrane bioreactor, direct anaerobic digestion, and constructed wetland, followed by ultraviolet light or chlorine disinfection. In most cases, gene fragments of SARS-CoV-2 were eliminated below the detection limit of RT-qPCR. The abundance of intI1 positively correlated with the sul1, OXA-10, and cphA-02 abundances; intI1 and the ARGs here studied were partially removed in the WWTPs, and in most cases, the number of copies per second discarded in the sludge were higher those in the effluent. The treatment processes decreased the abundance of dominant bacterial groups in the raw wastewater, while enriching bacterial groups in the effluent and the biological sludge, with possible pollutant removal capabilities. Bacterial communities in the raw wastewater showed the predominance of the genus Arcobacter (from 62.4 to 86.0 %) containing potentially pathogenic species. Additionally, DNA of some species persisted after the treatment processes: A. johnsonii, A. junii, A. caviae, A. hydrophila, A. veronii, A. butzleri, A. cryaerophilus, Chryseobacterium indologenes, Hafnia paralvei, M. osloensis, Pseudomonas putida and Vibrio cholerae, which deserves special attention in future regulation for safe water reuse.

18.
Environ Monit Assess ; 195(8): 975, 2023 Jul 20.
Article in English | MEDLINE | ID: mdl-37474709

ABSTRACT

The study explores the spatio-temporal variation of water quality parameters in the Hooghly estuary, which is considered an ecologically-stressed shallow estuary and a major distributary for the Ganges River. The estimated parameters are chlorophyll-a, total suspended matter (TSM), and chromophoric dissolved organic matter (CDOM). The Sentinel-3 OLCI remote sensing imageries were analyzed for the duration of October 2018 to February 2019. We observed that the water quality of the Hooghly estuaries is comparatively low-oxygenated, mesotrophic, and phosphate-limited. Ongoing channel dredging for maintaining shipping channel depth keeps the TSM in the estuary at an elevated level, with the highest amount of TSM observed during March of 2019 (41.59g m-3) at station A, upstream point. Since the pre-monsoon season, TSM data shows a decreasing trend towards the mouth of the estuary. Chl-a concentration is higher during pre-monsoon than monsoon and post-monsoon periods, with the highest value observed in April at 1.09 mg m-3 in station D during the pre-monsoon period. The CDOM concentration was high in the middle section (January-February) and gradually decreased towards the estuary's head and mouth. The highest CDOM was found in February at locations C and D during the pre-monsoon period. Every station shows a significant correlation among CDOM, TSM, and Chl-a measured parameters. Based on our satellite data analysis, it is recommended that SNAP C2RCC be regionally used for TSM, Chl-a, and CDOM for water quality product retrieval and in various algorithms for the Hooghly estuary monitoring.


Subject(s)
Environmental Monitoring , Water Quality , Estuaries , Chlorophyll A , Rivers
19.
Behav Sci (Basel) ; 13(7)2023 Jun 30.
Article in English | MEDLINE | ID: mdl-37503995

ABSTRACT

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterised by deficits in social interaction and communication, as well as restricted and stereotyped interests. Due of the high prevalence of gastrointestinal disorders in individuals with ASD, researchers have investigated the gut microbiota as a potential contributor to its aetiology. The relationship between the microbiome, gut, and brain (microbiome-gut-brain axis) has been acknowledged as a key factor in modulating brain function and social behaviour, but its connection to the aetiology of ASD is not well understood. Recently, there has been increasing attention on the relationship between the immune system, gastrointestinal disorders and neurological issues in ASD, particularly in relation to the loss of specific species or a decrease in microbial diversity. It focuses on how gut microbiota dysbiosis can affect gut permeability, immune function and microbiota metabolites in ASD. However, a very complete study suggests that dysbiosis is a consequence of the disease and that it has practically no effect on autistic manifestations. This is a review of the relationship between the immune system, microbial diversity and the microbiome-gut-brain axis in the development of autistic symptoms severity and a proposal of a novel role of gut microbiome in ASD, where dysbiosis is a consequence of ASD-related behaviour and where dysbiosis in turn accentuates the autistic manifestations of the patients via the microbiome-gut-brain axis in a feedback circuit.

20.
Sci Total Environ ; 887: 164057, 2023 Aug 20.
Article in English | MEDLINE | ID: mdl-37178842

ABSTRACT

Hospital effluents represent a threat to the environment owing to the content of toxic substances capable of altering the structure and function of ecosystems. Despite the available information about the impact of hospital effluents on aquatic organisms, the molecular mechanism underlying this process has received little or no attention. The present study aimed to evaluate the oxidative stress and gene expression induced by different proportions (2 %, 2.5 %, 3 % and 3.5 %) of hospital effluent treated by hospital wastewater treatment plant (HWWTP) in liver, gut, and gills of Danio rerio at different exposure times. Significant increases in the levels of protein carbonylation content (PCC), hydroperoxides content (HPC), lipoperoxidation level (LPX) and superoxide dismutase (SOD) and catalase (CAT) activity were observed in most of the organs evaluated at the four proportions tested with respect to the control group (p < 0.05). It was found that at longer exposure times there is a lower response in SOD activity, suggesting catalytic depletion due to the oxidative environment at the intracellular level. The lack of complementarity between SOD and mRNA activity patterns indicates that the activity itself is subordinated to post-transcriptional processes. Upregulation of transcripts related to antioxidant processes (sod, cat, nrf2), detoxification (cyp1a1) and apoptosis (bax, casp6, and casp9) was observed in response to oxidative imbalance. On the other hand, the metataxonomic approach allowed the characterization of pathogenic bacterial genera such as Legionella, Pseudomonas, Clostridium XI, Parachlamydia and Mycobacterium present in the hospital effluent. Our findings indicate that although hospital effluent was treated by HWWTP, it caused oxidative stress damage and disrupted gene expression by decreasing the antioxidant response in Danio rerio.


Subject(s)
Water Pollutants, Chemical , Zebrafish , Animals , Zebrafish/metabolism , Antioxidants/metabolism , Ecosystem , Oxidative Stress , Catalase/metabolism , Superoxide Dismutase/metabolism , Water Pollutants, Chemical/toxicity , Hospitals , Gene Expression
SELECTION OF CITATIONS
SEARCH DETAIL
...