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This study researches the impact of self-expansion experiences in the Metaverse on users' identity perception, self-esteem, and life satisfaction. To do so, the researchers conducted a two-wave panel study with a 3-month interval (N = 486) in VRChat, one of the most popular social virtual reality (VR) platforms. As predicted, the increase in self-expansion experience in VR environments positively predicted users' self-esteem and life satisfaction. However, when self-expansion led to a loss of coherency in the self-concept by causing identity disjunction or self-discrepancy, it damaged self-esteem and life satisfaction, respectively. The current findings exhibit that experimenting with and enlarging identity through immersive experiences in the Metaverse could benefit the individual, but only when it does not cause a disconnection between virtual and offline identities. This article discusses the potential opportunities and risks in the Metaverse, emphasizing the importance of advancing our understanding of the self-expansion experience in immersive media.
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Satisfação Pessoal , Realidade Virtual , Humanos , AutoimagemRESUMO
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently emerged as novel cardioprotective agents. However, their direct impact on cardiomyocyte injury is yet to be studied. In this work, we investigate the underlying molecular mechanisms of empagliflozin (EMPA), an SGLT2 inhibitor, in mitigating palmitate (PA)-induced cardiomyocyte injury in H9c2 cells. We found that EMPA significantly attenuated PA-induced impairments in insulin sensitivity, ER stress, inflammatory cytokine gene expression, and cellular apoptosis. Additionally, EMPA elevated AMP levels, activated the AMPK pathway, and increased carnitine palmitoyl transferase1 (CPT1) gene expression, which collectively enhanced fatty acid oxidation and reduced stress signals. This study reveals a novel mechanism of EMPA's protective effects against PA-induced cardiomyocyte injury, providing new therapeutic insights into EMPA as a cardioprotective agent.
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The accumulation of hepatic lipid droplets (LDs) is a hallmark of non-alcoholic fatty liver disease (NAFLD). Appropriate degradation of hepatic LDs and oxidation of complete free fatty acids (FFAs) are important for preventing the development of NAFLD. Histone deacetylase (HDAC) is involved in the impaired lipid metabolism seen in high-fat diet (HFD)-induced obese mice. Here, we evaluated the effect of MS-275, an inhibitor of HDAC1/3, on the degradation of hepatic LDs and FFA oxidation in HFD-induced NAFLD mice. To assess the dynamic degradation of hepatic LDs and FFA oxidation in fatty livers of MS-275-treated HFD C57BL/6J mice, an intravital two-photon imaging system was used and biochemical analysis was performed. The MS-275 improved hepatic metabolic alterations in HFD-induced fatty liver by increasing the dynamic degradation of hepatic LDs and the interaction between LDs and lysozyme in the fatty liver. Numerous peri-droplet mitochondria, lipolysis, and lipophagy were observed in the MS-275-treated mouse fatty liver. Biochemical analysis revealed that the lipolysis and autophagy pathways were activated in MS-275 treated mouse liver. In addition, MS-275 reduced the de novo lipogenesis, but increased the mitochondrial oxidation and the expression levels of oxidation-related genes, such as PPARa, MCAD, CPT1b, and FGF21. Taken together, these results suggest that MS-275 stimulates the degradation of hepatic LDs and mitochondrial free fatty acid oxidation, thus protecting against HFD-induced NAFLD.
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Hepatopatia Gordurosa não Alcoólica , Animais , Benzamidas , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos não Esterificados/metabolismo , Gotículas Lipídicas/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Hepatopatia Gordurosa não Alcoólica/metabolismo , PiridinasRESUMO
BACKGROUND: Choroid plexus papilloma represents 1-4% of pediatric brain tumors, mostly located in the ventricular atrium.[1] Intraventricular tumors represent a challenge due to the poor visualization of the surgical field and damage to surrounding structures.[2] Use of tubular retraction reduces cerebrovascular trauma to the surrounding parenchyma by distributing pressure uniformly, allowing less invasive corticotomy, and more stability on surgical corridors that allow the surgeon to use both hands and external visualization devices.[2-5]. CASE DESCRIPTION: We present the case of a 3-year-old boy with progressive headache, vomiting, and loss of control in the left hand for 3 months, with a history of ventricular shunt placement for acute obstructive hydrocephalus. The MRI revealed large lobulated lesion, which was hypointense on T1, hyperintense on T2, marked enhancement on T1 C+ (Gd) within the atrium of the right lateral ventricle, and spectroscopy with a peak of choline. Written consent for the use of photos and videos on this work was obtained from the patient's mother. A high-definition two-dimensional exoscope (VITOM® Karl Storz, Tuttlingen) was used during the surgical approach and throughout tumor removal, which was aided by ViewSite Brain Access System (VBAS®; Vycor Medical Inc.).[3] We performed a transparietal minimally invasive transsulcal parafascicular approach through the Frazier point for direct access to the ventricular atrium. Histological examination confirmed atypical choroid plexus papilloma. Postoperative imaging shows no residual tumor. The postoperative course was satisfactory with improvement of the headache and control of the left hand, leading to discharge home 1 week after surgery. CONCLUSION: The tubular transparietal minimally invasive approach obviates the need for traditional approaches to the atrium. This technique is safe and effective for the treatment of intraventricular and periventricular lesions, thus making this challenging target in more accessible to neurosurgeons, avoiding structure damage and any associated morbidity or mortality.
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The controllability of carrier density and major carrier type of transition metal dichalcogenides(TMDCs) is critical for electronic and optoelectronic device applications. To utilize doping in TMDC devices, it is important to understand the role of dopants in charge transport properties of TMDCs. Here, the effects of molecular doping on the charge transport properties of tungsten diselenide (WSe2 ) are investigated using three p-type molecular dopants, 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4 -TCNQ), tris(4-bromophenyl)ammoniumyl hexachloroantimonate (magic blue), and molybdenum tris(1,2-bis(trifluoromethyl)ethane-1,2-dithiolene) (Mo(tfd-COCF3 )3 ). The temperature-dependent transport measurements show that the dopant counterions on WSe2 surface can induce Coulomb scattering in WSe2 channel and the degree of scattering is significantly dependent on the dopant. Furthermore, the quantitative analysis revealed that the amount of charge transfer between WSe2 and dopants is related to not only doping density, but also the contribution of each dopant ion toward Coulomb scattering. The first-principles density functional theory calculations show that the amount of charge transfer is mainly determined by intrinsic properties of the dopant molecules such as relative frontier orbital positions and their spin configurations. The authors' systematic investigation of the charge transport of doped TMDCs will be directly relevant for pursuing molecular routes for efficient and controllable doping in TMDC nanoelectronic devices.
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Histone deacetylase (HDAC) inhibitors, which regulate gene expression by inhibiting the deacetylation of histones and nonhistone proteins, have been shown to exert a wide array of biological effects; these include anti-cancer, anti-obesity, and anti-diabetes effects, as well as cardiovascular-protective activity. However, the effects of class I HDAC inhibition on lipotoxicity in C2C12 myotubes and skeletal muscle tissue remain poorly understood. In this study, we investigated the molecular mechanism underlying the protective effect of class I HDAC inhibition under lipotoxic conditions, i.e., in palmitate (PA)-treated C2C12 myotubes and skeletal muscle tissue in high fat (HF)/high fructose (HFr) diet mice. PA treatment of C2C12 myotubes increased HDAC3 protein expression and impaired mitochondrial oxidation, resulting in increased mitochondrial ROS generation and an accumulation of intracellular triglycerides (TG). Prolonged exposure led to increased inflammatory cytokine expression and insulin resistance. In contrast, MS-275, a class I HDAC inhibitor, dramatically attenuated lipotoxicity, preventing PA-induced insulin resistance and inflammatory cytokine expression. Similar beneficial effects were also seen following HDAC3 knockdown. In addition, MS-275 increased the mRNA expression of peroxisome proliferator activator receptor γ-coactivator 1α (PGC1α) and mitochondrial transcription factor A (TFAM), which serve as transcriptional coactivators in the context of mitochondrial metabolism and biogenesis, and restored expression of peroxisome proliferator-activated receptor alpha (PPARα), medium-chain acyl-coenzyme A dehydrogenase (MCAD), enoyl-CoA hydratase, and 3-hydroxyacyl CoA dehydrogenase (EHHADH). In vivo, treatment of HF/HFr-fed mice with MS-275 ameliorated hyperglycemia, insulin resistance, stress signals, and TNF-α expression in skeletal muscle. Taken together, these results suggest that HDAC3 inhibition rather than HDAC1/2 inhibition by MS-275 protects against lipotoxicity in C2C12 myotubes and skeletal muscle, and may be effective for the treatment of obesity and insulin resistance.
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Early detection of asymptomatic coronary artery disease (CAD) is essential but underdeveloped. The aim of this study was to assess micro-RNA (miRNA) expression profiles in patients with or without CAD as selected by coronary CT angiography (CTA) and stratified by risk of CAD as determined by Framingham Risk Score (FRS). In this pilot study, patients were divided into two groups based on the presence or absence of CAD. Disease status was determined by Coronary CTA by identification of atherosclerosis and/or calcified plaque in coronary arteries. There were 16 control subjects and 16 subjects with documented CAD. Groups were then subdivided based on FRS. Pathway-specific microarray profiling of 86 genes using miRNAs isolated from whole peripheral blood was analyzed. MiRNA were differentially expressed in patients with and without CAD and who were stratified on the basis of FRS with miRNA associated with endothelial function, cardiomyocyte protection and inflammatory response (hsa-miR-17-5p, hsa-miR-21-5p, hsa-miR-210-3p, hsa-miR-29b-3p, hsa-miR-7-5p and hsa-miR-99a-5p) consistently upregulated by greater than twofold in groups with CAD. The present study reveals that miRNA expression patterns in whole blood as selected on the basis of coronary CTA and risk scores vary significantly depending on the subject phenotype. Thus, profiling miRNA may improve early detection of CAD.
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The buildup of pressure drop with mass loading of particles aggravates the breathing resistance and energy consumption of filters. This study investigated the role of intra- and interlayer space of filter media on the pressure drop development with continued particle loading. Five basic morphologies, including microfibers, nanofibers, microbeads-on-strings, and a mix of those morphologies were fabricated via electrospinning. Then the variations of layered constructions were made, to include a total 14 different filter structures. For a single layer filter media, the pore size rather than the percent porosity had a major impact on the pressure drop. For dual layers, the space between the layers and the placement order of webs were important factors affecting the pressure drop and depth loading of particles. Computational modeling was used to interpret the role of the interlayer space on the pressure drop, by monitoring the air flow and particle movement within the filter constructions, where the computational prediction corresponded to the tendency of the experimental findings. The novelty of this study lies in the combined approach of the experimental and computational work to understand the particle capture phenomenon during the mass loading.
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BACKGROUND: The opticocarotid triangle (OCT) and the carotico-oculomotor triangle (COT) are two anatomical triangles used in accessing the interpeduncular region. Our objective is to evaluate if the anterior incisural width (AIW) is an indicator to predict the intraoperative exposure through both triangles. METHODS: Twenty sides of 10 cadaveric heads were dissected and analyzed. The heads were divided into the following: Group A - narrow anterior incisura and Group B - wide anterior incisura - using 26.6 mm as a cutoff distance of the AIW. Subsequently, the area of the COT and the OCT in the transsylvian approach was measured, along with the maximum widths through the two trajectories in modified superior transcavernous approach. RESULTS: The COT in the wide group was shown to have a significantly larger area compared with the COT in the narrow group (38.4 ± 12.64 vs. 58.3 ± 15.72 mm, P < 0.01). No difference between the two groups was reported in terms of the area of the OCT (50.9 ± 19.22 mm vs. 63.5 ± 15.53 mm, P = 0.20), the maximum width of the OCT (6.6 ± 1.89 vs. 6.5 ± 1.38 mm, P = 1.00), or the maximum width of the COT (11.7 ± 2.06 vs. 12.2 ± 2.32 mm, P = 0.50). Clinical cases were included. CONCLUSION: An AIW <26.6 mm is an unfavorable factor related to a limited COT area in a transsylvian approach for pathologies at the interpeduncular fossa. Preoperative identification and measurement of a narrow AIW can suggest the need to add a transcavernous approach.
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In this study, we demonstrated the molecular ensemble junctions fabricated by the inverted selfassembled monolayer (iSAM) method in which the molecular layer was deposited on the top electrode surface. The alkyl thiolate molecules were used to benchmark this method and we found that the electrical characteristics of these molecular junctions were comparable to the results reported previously by performing statistical analysis. We expect this iSAM method to enable the molecular junctions with bottom electrode of various materials.
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Transcranial Doppler ultrasonography (TCD) is a noninvasive technique used to detect vasospasms following a subarachnoid hemorrhage. While the gold standard to evaluate vasospasms is angiography, this technique is invasive and poses additional risks as compared to TCD. TCD is performed by insonating circle of Willis arteries to measure cerebral flow velocity. TCD allows dynamic monitoring of CBF-V and vessel pulsatility, with a high temporal resolution. It is relatively inexpensive, repeatable, and portable; however, the performance of TCD is highly operator dependent and can be difficult, especially with inadequate acoustic windows. This review summarizes the use of transcranial Doppler ultrasonography (TCD) for the assessment of cerebral vasospasm.
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Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Humanos , Hemorragia Subaracnóidea/diagnóstico por imagem , Ultrassonografia Doppler Transcraniana , Vasoespasmo Intracraniano/diagnóstico por imagemRESUMO
: Purpose: A variety of treatment plans including an array of prescription doses have been used in radiosurgery treatment of trigeminal neuralgia (TN). However, despite a considerable experience in the radiosurgical treatment of TN, an ideal prescription dose that balances facial dysesthesia risk with pain relief durability has not been determined. METHODS AND MATERIALS: This retrospective study of patients treated with radiosurgery for typical TN evaluates two treatment doses in relation to outcomes of pain freedom, bothersome facial numbness, and patient satisfaction with treatment. All patients were treated with radiosurgery for intractable and disabling TN. A treatment dose protocol change from 80 to 85 Gy provided an opportunity to compare two prescription doses. The variables evaluated were pain relief, treatment side-effect profile, and patient satisfaction. RESULTS: Typical TN was treated with 80 Gy in 26 patients, and 85 Gy in 37 patients. A new face sensory disturbance was reported after 80 Gy in 16% and after 85 Gy in 27% (p = 0.4). Thirteen failed an 80 Gy dose whereas seven failed an 85 Gy dose. Kaplan-Meier analysis found that at 29 months 50% failed an 80 Gy treatment compared with 79% who had durable pain relief after 85 Gy treatment (p = 0.04). CONCLUSION: The 85 Gy dose for TN provided a more durable pain relief compared to the 80 Gy one without a significantly elevated occurrence of facial sensory disturbance.
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Strokes are one of the leading causes of mortality and chronic morbidity in the world, yet with only limited successful interventions available at present. Our previous studies revealed the potential role of the glucocorticoid receptor (GR) in the pathogenesis of neonatal hypoxic-ischemic encephalopathy (HIE). In the present study, we investigate the effect of GR knockdown on acute ischemic brain injuries in a model of focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO) in adult male CD1 mice. GR siRNAs and the negative control were administered via intracerebroventricular (i.c.v.) injection 48 h prior to MCAO. The cerebral infarction volume and neurobehavioral deficits were determined 48 h after MCAO. RT-qPCR was employed to assess the inflammation-related gene expression profiles in the brain before and after MCAO. Western Blotting was used to evaluate the expression levels of GR, the mineralocorticoid receptor (MR) and the brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) signaling. The siRNAs treatment decreased GR, but not MR, protein expression, and significantly enhanced expression levels of pro-inflammatory cytokines (IL-6, IL-1ß, and TNF-α) in the brain. Of interest, GR knockdown suppressed BDNF/TrkB signaling in adult mice brains. Importantly, GR siRNA pretreatment significantly increased the infarction size and exacerbated the neurobehavioral deficits induced by MCAO in comparison to the control group. Thus, the present study demonstrates the important role of GR in the regulation of the inflammatory responses and neurotrophic BDNF/TrkB signaling pathway in acute ischemic brain injuries in adult mice, revealing a new insight into the pathogenesis and therapeutic potential in acute ischemic strokes.
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Encéfalo/patologia , Infarto da Artéria Cerebral Média/genética , Infarto da Artéria Cerebral Média/patologia , Receptores de Glucocorticoides/genética , Animais , Encéfalo/metabolismo , Técnicas de Silenciamento de Genes , Infarto da Artéria Cerebral Média/metabolismo , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Interferência de RNA , RNA Interferente Pequeno/genética , Receptores de Glucocorticoides/metabolismo , Transdução de SinaisRESUMO
We developed a facile method to achieve a homogeneous coating of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) on a graphene oxide (GO) layer with outstanding sheet resistance. We fabricated a transparent bilayer GO/PEDOT:PSS film as a flexible transparent conductive electrode (TCF). GO layer was coated on flexible PET and PI substrate by dip coating. The coated GO layers were modulated by their sizes and post heat treatment. The GO layers were thermally reduced and over coated with a PEDOT:PSS layer. Compared to the values of PEDOT:PSS, the sheet resistance of the bilayer film decreased by 5.2% and cyclic bending durability increased by 47.4%. The synergetic conductive network between the reduced graphene oxide (RGO) layer and the PEDOT:PSS layer resulted in low sheet resistance; the initial network retained under cyclic bending. The bilayer TCF film can be applied to multifunctional electrical devices for which flexibility and high conductivity are necessary.
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Large studies in humans and animals have demonstrated a clear association of an adverse intrauterine environment with an increased risk of cardiovascular disease later in life. Yet mechanisms remain largely elusive. The present study tested the hypothesis that gestational hypoxia leads to promoter hypermethylation and epigenetic repression of the glucocorticoid receptor (GR) gene in the developing heart, resulting in increased heart susceptibility to ischemia and reperfusion injury in offspring. Hypoxic treatment of pregnant rats from day 15 to 21 of gestation resulted in a significant decrease of GR exon 14, 15, 16, and 17 transcripts, leading to down-regulation of GR mRNA and protein in the fetal heart. Functional cAMP-response elements (CREs) at -4408 and -3896 and Sp1 binding sites at -3425 and -3034 were identified at GR untranslated exon 1 promoters. Hypoxia significantly increased CpG methylation at the CREs and Sp1 binding sites and decreased transcription factor binding to GR exon 1 promoter, accounting for the repression of the GR gene in the developing heart. Of importance, treatment of newborn pups with 5-aza-2'-deoxycytidine reversed hypoxia-induced promoter methylation, restored GR expression and prevented hypoxia-mediated increase in ischemia and reperfusion injury of the heart in offspring. The findings demonstrate a novel mechanism of epigenetic repression of the GR gene in fetal stress-mediated programming of ischemic-sensitive phenotype in the heart.
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Epigênese Genética , Hipóxia/genética , Traumatismo por Reperfusão Miocárdica/genética , Oxigênio/farmacologia , Receptores de Glucocorticoides/genética , Fator de Transcrição Sp1/genética , Animais , Animais Recém-Nascidos , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Sítios de Ligação , Metilação de DNA/efeitos dos fármacos , Decitabina , Éxons , Feminino , Hipóxia/tratamento farmacológico , Hipóxia/metabolismo , Hipóxia/patologia , Masculino , Exposição Materna , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Fenótipo , Gravidez , Regiões Promotoras Genéticas , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Receptores de Glucocorticoides/antagonistas & inibidores , Receptores de Glucocorticoides/metabolismo , Elementos de Resposta , Fator de Transcrição Sp1/metabolismoRESUMO
Dry density and water content are two important factors affecting the degree of soil compaction. Conventional methods such as the sand cone test and the plate load test are used to measure such properties for evaluating the degree of compaction and the stiffness of soil in the field. However, these tests are generally very time-consuming and are inherent with some errors depending on the operator (in particular for the sand cone test). Elastic modulus is an indicator to describe the stress-strain behavior of soil and in some cases is used as a design input parameter. Although a rod type TDR (Time Domain Reflectometry) system has been recently proposed to overcome some shortcomings of the conventional methods (particularly the sand cone test), it requires driving the probes into the ground, thus implying that it is still a time-consuming and destructive testing method. This study aims to develop a new non-destructive TDR system that can rapidly measure the dry density, water content, and elastic modulus of soil on the surface of compacted soil, without disturbing the ground. In this study, the Piezoelectric Stack, which is an instrument for measuring the elastic modulus of soil, has been added to the TDR system with a flat type probe, leading to a non-destructive TDR system that is capable of measuring the dry density, water content, and elastic modulus of soil. The new TDR system developed is light enough for an engineer to carry. Results of the standard compaction and TDR tests on sand showed that the dry densities and the moisture contents measured with the new TDR system were in good agreement with those measured with the standard compaction test, respectively. Consequently, it appears that the new TDR system developed will be very useful to advance the current practice of compaction quality control.
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Inhibition of angiotensin II type 1 receptor (AT1R) is an important therapy in the management of hypertension, particularly in the immediate post-myocardial infarction period. Yet, the role of AT1R in the acute onset of myocardial ischemia and reperfusion injury still remains controversial. Thus, the present study determined the effects of chronic losartan treatment on heart ischemia and reperfusion injury in rats. Losartan (10 mg/kg/day) was administered to six-month-old male rats via an osmotic pump for 14 days and hearts were then isolated and were subjected to ischemia and reperfusion injury in a Langendorff preparation. Losartan significantly decreased mean arterial blood pressure. However, heart weight, left ventricle to body weight ratio and baseline cardiac function were not significantly altered by the losartan treatment. Of interest, chronic in vivo losartan treatment significantly increased ischemia-induced myocardial injury and decreased post-ischemic recovery of left ventricular function. This was associated with significant increases in AT1R and PKCδ expression in the left ventricle. In contrast, AT2R and PKCε were not altered. Furthermore, losartan treatment significantly increased microRNA (miR)-1, -15b, -92a, -133a, -133b, -210, and -499 expression but decreased miR-21 in the left ventricle. Of importance, addition of losartan to isolated heart preparations blocked the effect of increased ischemic-injury induced by in vivo chronic losartan treatment. The results demonstrate that chronic losartan treatment up-regulates AT1R/PKCδ and alters miR expression patterns in the heart, leading to increased cardiac vulnerability to ischemia and reperfusion injury.
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Bloqueadores do Receptor Tipo 2 de Angiotensina II/farmacologia , Coração/efeitos dos fármacos , Losartan/farmacologia , Traumatismo por Reperfusão/induzido quimicamente , Regulação para Cima/efeitos dos fármacos , Bloqueadores do Receptor Tipo 2 de Angiotensina II/efeitos adversos , Animais , Losartan/efeitos adversos , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Recent studies provide evidence that ischemic preconditioning (IP) and ischemia/reperfusion (IR) injury lead to altered expression of microRNAs (miRNAs) that affect the survival and recovery of cardiomyocytes. These endogenous â¼22-nucleotide noncoding RNAs negatively regulate gene expression via degradation and translational inhibition of their target mRNAs. miRNAs are involved in differentiation, proliferation, electrical conduction, angiogenesis and apoptosis. These pathways can lead to physiological and pathological adaptations. This review intends to explore several facets of miRNA expression and the underlying mechanisms involved in IR injury, as well as IP as a cardioprotective strategy. In addition, we will investigate miRNA interaction with the renin-angiotensin system and the potential use of miRNAs in developing sensitive biomarkers for cardiovascular disease.
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MicroRNAs , Isquemia Miocárdica/genética , Animais , Biomarcadores/metabolismo , Humanos , Precondicionamento Isquêmico Miocárdico , MicroRNAs/genética , MicroRNAs/metabolismo , Sistema Renina-AngiotensinaRESUMO
Ceramide has been suggested to participate in the neuronal cell death that leads to Alzheimer's disease (AD), but its role is not yet well-understood. We compared the levels of six ceramide subspecies, which differ in the length of their fatty acid moieties, in brains from patients who suffered from AD, other neuropathological disorders, or both. We found elevated levels of Cer16, Cer18, Cer20, and Cer24 in brains from patients with any of the tested neural defects. Moreover, ceramide levels were highest in patients with more than one neuropathologic abnormality. Interestingly, the range of values was higher among brains with neural defects than in controls, suggesting that the regulation of ceramide synthesis is normally under tight control, and that this tight control may be lost during neurodegeneration. These changes, however, did not alter the ratio between the tested ceramide species. To explore the mechanisms underlying this dysregulation, we evaluated the expression of four genes connected to ceramide metabolism: ASMase, NSMase 2, GALC, and UGCG. The patterns of gene expression were complex, but overall, ASMase, NSMase 2, and GALC were upregulated in specimens from patients with neuropathologic abnormalities in comparison with age-matched controls. Such findings suggest these genes as attractive candidates both for diagnostic purposes and for intervening in neurodegenerative processes.
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Doença de Alzheimer/patologia , Encéfalo/metabolismo , Ceramidas/metabolismo , Doenças Neurodegenerativas/patologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Ceramidas/genética , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Galactosilceramidase/genética , Galactosilceramidase/metabolismo , Regulação da Expressão Gênica , Humanos , Masculino , RNA Mensageiro/metabolismo , Esfingomielina Fosfodiesterase/genética , Esfingomielina Fosfodiesterase/metabolismo , Espectrometria de Massas em TandemRESUMO
A beta-ionone-resistant mutant strain isolated from the red yeast Xanthophyllomyces dendrorhous KCTC 7704 was used for batch and continuous fermentation kinetic studies with glucose media in a 2.5-1 jar fermentor at 22 degrees C and pH 4.5. The kinetic pattern of growth and carotenoid concentration in the batch fermentations exhibited a so-called mixed-growth-associated product formation, possibly due to the fact that the content of intracellular carotenoids depends on the degree of physical maturation toward adulthood. To determine the maximum specific growth rate constant (microm) and Monod constant (k(s)) for the mutant, glucose-limited continuous culture studies were performed at different dilution rates within a range of 0.02-0.10 h(-1). A reciprocal plot of the steady-state data (viz., reciprocal of glucose concentration versus residence time) obtained from continuous culture experiments was used to estimate a microm of 0.15 h(-1) and k(s) of 1.19 g/l. The carotenoid content related to the residence time appeared to assume a typical form of saturation kinetics. The maximum carotenoid content (Xm) for the mutant was estimated to be 1.04 microg/mg dry cell weight, and the Lee constant (k(m)), which was tentatively defined in this work, was found to be 3.0 h.