Neuronal damage resulting from traumatic brain injury (TBI) causes disruption of neuronal projections and neurotransmission that contribute to behavioral deficits. Cellular generation of reactive ...oxygen species (ROS) and reactive nitrogen species (RNS) is an early event following TBI. ROS often damage DNA, lipids, proteins, and carbohydrates while RNS attack proteins. The products of lipid peroxidation 4-hydroxynonenal (4-HNE) and protein nitration 3-nitrotyrosine (3-NT) are often used as indicators of oxidative and nitrosative damages, respectively. Increasing evidence has shown that striatum is vulnerable to damage from TBI with a disturbed dopamine neurotransmission. TBI results in neurodegeneration, oxidative stress, neuroinflammation, neuronal apoptosis, and autophagy in the striatum and contribute to motor or behavioral deficits. Pomalidomide (Pom) is a Food and Drug Administration (FDA)-approved immunomodulatory drug clinically used in treating multiple myeloma. We previously showed that Pom reduces neuroinflammation and neuronal death induced by TBI in rat cerebral cortex. Here, we further compared the effects of Pom in cortex and striatum focusing on neurodegeneration, oxidative and nitrosative damages, as well as neuroinflammation following TBI. Sprague-Dawley rats subjected to a controlled cortical impact were used as the animal model of TBI. Systemic administration of Pom (0.5 mg/kg, intravenous i.v.) at 5 h post-injury alleviated motor behavioral deficits, contusion volume at 24 h after TBI. Pom alleviated TBI-induced neurodegeneration stained by Fluoro-Jade C in both cortex and striatum. Notably, Pom treatment reduces oxidative and nitrosative damages in cortex and striatum and is more efficacious in striatum (93% reduction in 4-HNE-positive and 84% reduction in 3-NT-positive neurons) than in cerebral cortex (42% reduction in 4-HNE-positive and 55% reduction in 3-NT-positive neurons). In addition, Pom attenuated microgliosis, astrogliosis, and elevations of proinflammatory cytokines in cortical and striatal tissue. We conclude that Pom may contribute to improved motor behavioral outcomes after TBI through targeting oxidative/nitrosative damages and neuroinflammation.
The impact of sleep disorders (SDs), particularly sleep apnea (SA), on the development of colorectal cancer (CRC) has been the subject of significant research. However, the potential contribution of ...other SDs to the incidence of CRC remains unexplored. The objective of this study was to examine the effects of SDs on the risk of developing CRC. This study assessed CRC risk among individuals diagnosed with SDs compared with age- and sex-matched unaffected individuals. A longitudinal, nationwide, population-based cohort study was conducted using data from the Taiwan National Health Insurance Research Database (NHIRD) encompassing 177,707 individuals diagnosed with SDs and 177,707 matched controls. Cox proportional hazard regression analysis was used to determine the relative increased risk of CRC in individuals with SDs and specific subgroups of SDs. The CRC incidences were 1.32-fold higher (95% CI 1.23–1.42) in the overall SD cohort, 1.17-fold higher (95% CI 0.82–1.68) in the SA cohort, 1.42-fold higher (95% CI 1.31–1.55) in the insomnia cohort, 1.27-fold higher (95% CI 1.17–1.38) in the sleep disturbance cohort, and 1.00-fold higher (95% CI 0.77–1.29) in the other SD cohort, after adjusting for age, sex, and comorbidities.
Over 2 million people suffer from mild traumatic brain injury (mTBI) each year. Predicting symptoms of mTBI and the characterization of those symptoms has been challenging. Biomarkers that correlate ...clinical symptoms to disease outcome are desired to improve understanding of the disease and optimize patient care. Bone marrow kinase on chromosome X (BMX), a member of the TEC family of nonreceptor tyrosine kinases, is up-regulated after traumatic neural injury in a rat model of mTBI. The aim of this investigation was to determine whether BMX serum concentrations can effectively be used to predict outcomes after mTBI in a clinical setting. A total of 63 patients with mTBI (Glasgow Coma Score GCS between 13 and 15) were included. Blood samples taken at the time of hospital admission were analyzed for BMX. Data collected included demographic and clinical variables. Outcomes were assessed using the Dizziness Handicap Inventory (DHI) questionnaire at baseline and 6 weeks postinjury. The participant was asssigned to the case group if the subject's complaints of dizziness became worse at the sixth week assessment; otherwise, the participant was assigned to the control group. A receiver operating characteristic curve was constructed to explore BMX level. Significant associations were found between serum levels of BMX and dizziness. Areas under the curve for prediction of change in DHI postinjury were 0.76 for total score, 0.69 for physical score, 0.65 for emotional score, and 0.66 for functional score. Specificities were between 0.69 and 0.77 for total score and emotional score, respectively. Therefore, BMX demonstrates potential as a candidate serum biomarker of exacerbating dizziness post-mTBI.
Depression is one of the frequent complications following a mild traumatic brain injury (mTBI). Recent research indicated that abnormalities in the autonomic nervous system (ANS) can be evaluated by ...a noninvasive power spectral analysis of the heart rate variability (HRV). In this study, we investigated whether a frequency‐domain analysis of HRV was correlated with late depression in mTBI patients. In total, 181 patients diagnosed with mTBI and 83 volunteers as healthy controls were recruited in 2010–2014. Beck Depression Inventory (BDI) scores were used to evaluate depression in the 1st week of assessment and at 1.5‐, 3‐, 6‐, 12‐, and 18‐month follow‐ups. Correlation and logistic regression analyses of the 1st week HRV parameters with BDI scores at 18 months were performed in individual female mTBI patients. Female mTBI patients were more vulnerable to depression accompanied by reduced HRV compared to healthy controls. Over time, depression was aggravated in female mTBI patients but was alleviated in male mTBI patients. A significantly lower parasympathetic proportion of the ANS was noted at 18 months with respect to the 1st week in female mTBI patients. In addition, depression in female mTBI patients at 18 months after injury was significantly correlated with a decrease in the parasympathetic proportion of the ANS in the 1st week (ρ = −0.411; p < .05). Dysautonomia resulted in higher risks of depression in female mTBI patients. We concluded that early dysautonomia following an mTBI contributes to late depression in female mTBI patients.
Diabetes is associated with the development of myocardial fibrosis, which is related to various cardiac diseases. Cafestol, one of the active ingredients in coffee, has been reported to exert ...biological effects. However, whether cafestol can ameliorate diabetes-induced cardiac fibrosis remains unknown. The aim of this study was to evaluate the effects of cafestol on cardiac fibrosis in high-glucose-treated cardiac fibroblasts and streptozocin- (STZ-) induced diabetic rats. Rat cardiac fibroblasts were cultured in high-glucose (25 mM) media in the absence or presence of cafestol, and the changes in collagen synthesis, transforming growth factor-β1 (TGF-β1) production, and related signaling molecules were assessed on the basis of 3H-proline incorporation, enzyme-linked immunosorbent assay, and western blotting. Cardiac fibroblasts exposed to high-glucose conditions exhibited increased collagen synthesis, TGF-β1 production, and Smad2/3 phosphorylation, and these effects were mitigated by cafestol treatment. Furthermore, cafestol increased the translocation of nuclear factor erythroid 2-related factor 2 and increased the expression of heme oxygenase-1. The results of molecular docking analysis suggested a selective interaction of cafestol with Kelch-like ECH-associated protein 1. The rats with untreated STZ-induced diabetes exhibited considerable collagen accumulation, which was ameliorated by cafestol. Moreover, activities of catalase, superoxide dismutase, general matrix metalloproteinase, and reduced glutathione concentration were upregulated, whereas malondialdehyde level was downregulated by treatment with cafestol in rats with cardiac fibrosis. These findings highlight the effects of cafestol, which may be useful in treating diabetes-related cardiac fibrosis.
Sustainable conservation aims to ensure the sustained conservation of landscape multi-functionality which in turn requires ensuring ecosystem service (ES) and habitat quality (HQ) sustainability with ...inclusive landscape-scale conservation planning. This study proposes a landscape conservation planning (LCP) framework for landscape-scale ES-HQ conservation and sustainability. Spatially explicit hotspots for five ESs and HQs are identified via InVEST and LISA software. Spatiotemporal changes in ES-HQ hotspots, in terms of stability and resilience, are delineated. The Zonation technique is applied to prioritize areas for conservation based on ES-HQ hotspot stability and resilience maps. High priority conservation areas are identified and are used as reserve area inputs for land use modeling with CLUE-S software to simulate future land use change under climate change scenarios. This study reports that varied rainfall and climate are major driving factors of ES-HQ sustainability disturbance in the study area. Furthermore, our proposed conservation Strategy 2 demonstrates that a larger extent of landscape multi-functionality can be sustained when the existing conservation area includes the total area of identified ES-HQ resilient hotspots. This study effectively identifies the stability and resiliency of ES-HQ hotspot areas affected by disturbances for high priority landscape conservation requirements to ensure ES-HQ sustainability and landscape multi-functionality in the study area.
In this study, we developed a novel in situ hydrothermal method to fabricate self-assembled P3HT/TiO2 hybrid nanowires, wherein a facile one-step synthetic strategy was utilized to co-organize P3HT ...molecules and titanium precursors into highly elongated hybrid nanowires, followed by a hydrothermal process in an autoclave to in situ transform the titanium precursors into crystalline TiO2 nanoparticles on the P3HT nanofibrils. P3HT nanofibrils were utilized as a structure-directing motif to achieve a favorable dispersion of electron acceptor (A) TiO2 nanocrystals of 10-15 nm in diameter embossed along the nanofibrils, as well as an efficient electron donor (D) for the nanohybrid. In particular, the crystallization temperature of anatase-phase TiO2 nanoparticles with high crystallinity obtained via the hydrothermal method was significantly reduced to 130 degree C in an elevated pressure of similar to 7 bars as compared to the conventional calcination temperature of 450 degree C at ambient pressure for TiO2 nanocrystal synthesis, therefore, allowing the synergistic one-step fabrication of both highly crystalline TiO2 nanoparticles embossed on highly crystalline long-range ordered P3HT nanofibrils. As a consequence of the structural development, this P3HT/TiO2 embossed nanohybrid could afford significant improvements in its D/A interfacial contact area for effective charge separation without the need for capping ligands typically used in ex situ D/A blend systems, as well as an efficient pathway for charge transport, leading to enhanced optoelectronic properties and device performance. The highest conversion efficiency of 0.14% was presented by the P3HT/TiO2 embossed hybrid device, which was a remarkable improvement as compared to only 0.03% from an ex situ P3HT/TiO2 hybrid device. This novel in situ approach shows a feasible way to fabricate organic/inorganic nanohybrid materials of conjugated copolymers with different inorganic nanoparticles for the applications of future optoelectronic devices.
Mild traumatic brain injury (mTBI) is a prevalent health concern with variable recovery trajectories, necessitating reliable prognostic markers. Insulin-like growth factor 1 (IGF-1) emerges as a ...potential candidate because of its role in cellular growth, repair, and neuroprotection. However, limited studies investigate IGF-1 as a prognostic marker in mTBI patients. This study aimed to explore the correlation of IGF-1 with cognitive functions assessed using the Wisconsin Card Sorting Test (WCST) in mTBI patients. We analyzed data from 295 mTBI and 200 healthy control participants, assessing demographic characteristics, injury causes, and IGF-1 levels. Cognitive functions were evaluated using the WCST. Correlation analyses and regression models were used to investigate the associations between IGF-1 levels, demographic factors, and WCST scores. Significant differences were observed between mTBI and control groups in the proportion of females and average education years. Falls and traffic accidents were identified as the primary causes of mTBI. The mTBI group demonstrated worse cognitive outcomes on the WCST, except for the "Learning to Learn" index. Correlation analyses revealed significant relationships between IGF-1 levels, demographic factors, and specific WCST scores. Regression models demonstrated that IGF-1, age, and education years significantly influenced various WCST scores, suggesting their roles as potential prognostic markers for cognitive outcomes in mTBI patients. We provide valuable insights into the potential correlation of IGF-1 with cognitive functions in mTBI patients, particularly in tasks requiring cognitive flexibility and problem solving.
This study investigated whether lipopolysaccharide (LPS) increase protease-activated receptor-2 (PAR-2) expression and enhance the association between PAR-2 expression and chemokine production in ...human vascular endothelial cells (ECs).
The morphology of ECs was observed through microphotography in cultured human umbilical vein ECs (EA. hy926 cells) treated with various LPS concentrations (0, 0.25, 0.5, 1, and 2 μg/mL) for 24 h, and cell viability was assessed using the MTT assay. Intracellular calcium imaging was performed to assess agonist (trypsin)-induced PAR-2 activity. Western blotting was used to explore the LPS-mediated signal transduction pathway and the expression of PAR-2 and adhesion molecule monocyte chemoattractant protein-1 (MCP-1) in ECs.
Trypsin stimulation increased intracellular calcium release in ECs. The calcium influx was augmented in cells pretreated with a high LPS concentration (1 μg/mL). After 24 h treatment of LPS, no changes in ECs viability or morphology were observed. Western blotting revealed that LPS increased PAR-2 expression and enhanced trypsin-induced extracellular signal-regulated kinase (ERK)/p38 phosphorylation and MCP-1 secretion. However, pretreatment with selective ERK (PD98059), p38 mitogen-activated protein kinase (MAPK) (SB203580) inhibitors, and the selective PAR-2 antagonist (FSLLRY-NH2) blocked the effects of LPS-activated PAR-2 on MCP-1 secretion.
Our findings provide the first evidence that the bacterial endotoxin LPS potentiates calcium mobilization and ERK/p38 MAPK pathway activation and leads to the secretion of the pro-inflammatory chemokine MCP-1 by inducing PAR-2 expression and its associated activity in vascular ECs. Therefore, PAR-2 exerts vascular inflammatory effects and plays an important role in bacterial infection-induced pathological responses.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background: Endovascular thrombectomy (EVT) for acute ischemic stroke associated with tandem lesion is challenging. Achieving rapid intracranial revascularization and managing the extracranial lesion ...without complications are the main challenges.
Materials and Methods: The balloon angioplasty followed by aspiration of large-vessel occlusion (BAFALO) technique was used to address this clinical issue. A review of a prospectively maintained stroke registry from January 2015 to April 2020 was performed. Patients had stroke with TO and treated with the BAFALO technique were included.
Results: Twelve patients were enrolled: 11 had anterior circulation stroke, and 1 had posterior circulation stroke. There were 10 ipsilateral internal carotid artery stenosis/occlusion, one left common carotid artery to subclavian artery bypass stenosis, and 1 vertebral artery orifice stenosis. The median National Institutes of Health Stroke Scale score was 16 (interquartile range IQR: 14-16). Revascularization with a Modified Thrombolysis in Cerebral Infarction score of 2b or more was achieved in 11 (92%) patients. The median puncture-to-revascularization time was 25 min (IQR: 19.5-31). Emergent stent implantation was performed in five (42%) patients. Three had distal protection devices (DPDs) with no distal embolization. Two patients did not use a DPD, and one had intracranial reocclusion. Eight (67%) proximal stenotic vessels remained patent. No symptomatic intracranial hemorrhage occurred. Eight (67%) patients had favorable clinical outcomes (modified Rankin Score 0-2 at 90 days).
Conclusion: While managing TO, the BAFALO technique could achieve rapid intracranial revascularization and treat extracranial lesions under embolic protection. These merits translate into favorable clinical outcomes.
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