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It has been shown that prostaglandin (PG) E2 synthesized in the lateral parabrachial nucleus (LPBN) is involved in lipopolysaccharide-induced fever. But the neural mechanisms of how intra-LPBN PGE2 induces fever remain unclear. In this study, we investigated whether the LPBN-preoptic area (POA) pathway, the thermoafferent pathway for feed-forward thermoregulatory responses, mediates fever induced by intra-LPBN PGE2 in male rats. The core temperature (Tcore) was monitored using a temperature radiotelemetry transponder implanted in rat abdomen. We showed that microinjection of PGE2 (0.28 nmol) into the LPBN significantly enhanced the density of c-Fos-positive neurons in the median preoptic area (MnPO). The chemical lesioning of MnPO with ibotenate or selective genetic lesioning or inhibition of the LPBN-MnPO pathway significantly attenuated fever induced by intra-LPBN injection of PGE2. We demonstrated that EP3 receptor was a pivotal receptor for PGE2-induced fever, since microinjection of EP3 receptor agonist sulprostone (0.2 nmol) or EP3 receptor antagonist L-798106 (2 nmol) into the LPBN mimicked or weakened the pyrogenic action of LPBN PGE2, respectively, but this was not the case for EP4 and EP1 receptors. Whole-cell recording from acute LPBN slices revealed that the majority of MnPO-projecting neurons originating from the external lateral (el) and dorsal (d) LPBN were excited and inhibited, respectively, by PGE2 perfusion, initiating heat-gain and heat-loss mechanisms. The amplitude but not the frequency of spontaneous and miniature glutamatergic excitatory postsynaptic currents (sEPSCs and mEPSCs) in MnPO-projecting LPBel neurons increased after perfusion with PGE2; whereas the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) and the A-type potassium (IA) current density did not change. In MnPO-projecting LPBd neurons, neither sEPSCs nor sIPSCs responded to PGE2; however, the IA current density was significantly increased by PGE2 perfusion. These electrophysiological responses and the thermoeffector reactions to intra-LPBN PGE2 injection, including increased brown adipose tissue thermogenesis, shivering, and decreased heat dissipation, were all abolished by L-798106, and mimicked by sulprostone. These results suggest that the pyrogenic effects of intra-LPBN PGE2 are mediated by both the inhibition of the LPBd-POA pathway through the EP3 receptor-mediated activation of IA currents and the activation of the LPBel-POA pathway through the selective enhancement of glutamatergic synaptic transmission via EP3 receptors.
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Regulação da Temperatura Corporal , Dinoprostona , Febre , Núcleos Parabraquiais , Área Pré-Óptica , Receptores de Prostaglandina E Subtipo EP3 , Animais , Masculino , Ratos , Regulação da Temperatura Corporal/efeitos dos fármacos , Dinoprostona/farmacologia , Febre/induzido quimicamente , Febre/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Núcleos Parabraquiais/efeitos dos fármacos , Núcleos Parabraquiais/fisiologia , Área Pré-Óptica/efeitos dos fármacos , Área Pré-Óptica/metabolismo , Ratos Sprague-Dawley , Receptores de Prostaglandina E Subtipo EP3/metabolismoRESUMO
Pursuing effective and generalized strategies for modulating the electronic structures of atomically dispersed nanozymes with remarkable catalytic performance is exceptionally attractive yet challenging. Herein, we developed a facile "formamide condensation and carbonization" strategy to fabricate a library of single-atom (M1-NC; 6 types) and dual-atom (M1/M2-NC; 13 types) metal-nitrogen-carbon nanozymes (M = Fe, Co, Ni, Mn, Ru, Cu) to reveal peroxidase- (POD-) like activities. The Fe1Co1-NC dual-atom nanozyme with Fe1-N4/Co1-N4 coordination displayed the highest POD-like activity. Density functional theory (DFT) calculations revealed that the Co atom site synergistically affects the d-band center position of the Fe atom site and served as the second reaction center, which contributes to better POD-like activity. Finally, Fe1Co1 NC was shown to be effective in inhibiting tumor growth both in vitro and in vivo, suggesting that diatomic synergy is an effective strategy for developing artificial nanozymes as novel nanocatalytic therapeutics.
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Peroxidase , Peroxidases , Carbono , Catálise , CorantesRESUMO
Agmatine is an endogenous biogenic amine that exerts various effects on the central nervous system. The hypothalamic preoptic area (POA, thermoregulatory command center) has high agmatine immunoreactivity. In this study, in conscious and anesthetized male rats, agmatine microinjection into the POA induced hyperthermic responses associated with increased heat production and locomotor activity. Intra-POA administration of agmatine increased the locomotor activity, the brown adipose tissue temperature and rectum temperature, and induced shivering as demonstrated by increased neck muscle electromyographic activity. However, intra-POA administration of agmatine almost had no impact on the tail temperature of anesthetized rats. Furthermore, there were regional differences in the response to agmatine in the POA. The most effective sites for the microinjection of agmatine to elicit hyperthermic responses were localized in the medial preoptic area (MPA). Agmatine microinjection into the median preoptic nucleus (MnPO) and lateral preoptic nucleus (LPO) had a minimal effect on the mean core temperature. Analysis of the in vitro discharge activity of POA neurons in brain slices when perfused with agmatine showed that agmatine inhibited most warm-sensitive but not temperature-insensitive neurons in the MPA. However, regardless of thermosensitivity, the majority of MnPO and LPO neurons were not responsive to agmatine. The results demonstrated that agmatine injection into the POA of male rats, especially the MPA, induced hyperthermic responses, which may be associated with increased BAT thermogenesis, shivering and locomotor activity by inhibiting warm-sensitive neurons.
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Agmatina , Área Pré-Óptica , Ratos , Masculino , Animais , Área Pré-Óptica/fisiologia , Agmatina/farmacologia , Regulação da Temperatura Corporal/fisiologia , Hipotálamo , EstremecimentoRESUMO
The point-of-care (POC) method with affordability and portability for the sensitive detection of biological substances is an emerging topic in rapid disease screening and personalized medicine. In this work, we demonstrated a diverse responsive platform based on a dual-channel pressure sensor (DCPS). The DCPS had a multilayer flexible architecture consisting of a photonic hydrogel with chromatic transitions and a piezoresistive pressure sensor as the electrical data transmission unit, both of which had the property of pressure-induced mechanical stimulus feedback. By incorporating a platinum nanoparticles-labeled detection antibody (PtNPs-dAb) into the sandwich-type immunoreaction for the target carcinoembryonic antigen (CEA, as a model analyte), gas decomposition could be triggered by the addition of hydrogen peroxide (H2O2) to induce a significant increase under pressure in a closed chamber. Meanwhile, the DCPS enabled an accurate electrical signal output, and the photonic hydrogel converted spatiotemporal stimuli into eye-readable colorations with string brilliance. In this way, the target concentration could be quantificationally related to the electrical response and intuitively perceived through visible color alterations. Under optimal conditions, a sensitive determination of CEA was performed in a detectable range of 0.3-60 ng/mL with a limit of detection (LOD) of 0.13 ng/mL. In addition, the proposed protocol had satisfactory selectivity, accuracy, and reproducibility. Furthermore, an array-based immunoassay device was fabricated to conceptually validate its application potential in high-throughput biomedical detection and inspire a dual-signal POC diagnostic platform in a friendly way for resource-limited settings.
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Técnicas Biossensoriais , Nanopartículas Metálicas , Antígeno Carcinoembrionário , Ouro , Hidrogéis , Peróxido de Hidrogênio , Imunoensaio/métodos , Limite de Detecção , Platina , Sistemas Automatizados de Assistência Junto ao Leito , Reprodutibilidade dos TestesRESUMO
A magnetic-assisted photoelectrochemical (PEC) and colorimetric (CL) dual-modal biosensing platform with high precision was established to monitor prostate-specific antigen (PSA) based on Bi2MoO6 nanosheets (BMO) by coupling the aptamer-guided hybridization chain reaction (HCR) with the hydrolysate-induced vulcanization reaction of Bi2MoO6 nanosheets. Upon addition of PSA, trigger DNA (tDNA) was released by the interaction between the target analyte and the aptamer and then further hybridized with anchor DNA (aDNA) conjugated on magnetic beads (MBs). The as-released tDNA initiated the target-assisted HCR in the presence of two alternating hairpin sequences (Bio-H1 and Bio-H2) to produce nicked long double-stranded DNA on the surface of MBs, where numerous alkaline phosphatase (ALP) enzymes could assemble with MBs through the biotin-avidin reaction, resulting in the hydrolysis of sodium thiophosphate (TP) to H2S. The as-produced H2S reacted with BMO to form vulcanized BMO (BMO-S), thus leading to obvious enhanced PEC performance under visible light with the color change from light yellow to brown. Having optimized the test conditions, the magnetic-assisted biosensing system holds a good quantitative diagnosis sensitivity area in a range of 5.0 pg mL-1-100 ng mL-1 with a calculated detection limit down to 3.5 pg mL-1. Meanwhile, a visual colorimetric assay on basis of the change in the color of the materials was also realized. Given the exceptional performance of the constructed biosensor, it may possess great promise as an advanced bioanalytical tool for practical applications.
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Técnicas Biossensoriais , Antígeno Prostático Específico , Biocatálise , Bismuto , DNA , Técnicas Eletroquímicas/métodos , Humanos , Limite de Detecção , Masculino , MolibdênioRESUMO
Point-of-care testing (POCT) technology has made major breakthroughs in community medicine and physician office situations, in tandem with the more ubiquitous and intensive usage of highly integrated quick detection equipment for illness diagnosis, personal care, and mobile healthcare. Although the photoelectrochemical (PEC)-based POCT platform offers the benefits of cheap cost and good user engagement, its commercialization is still limited by the photodetection components' downsizing and mobility, among other factors. In this work, a novel highly integrated PEC biosensor aided by piezophototronics to enhance the efficiency of PEC testing was reported for flexible detection of cancer-associated antigens in biological fluids (prostate-specific antigen, PSA, used as an example). Multiple signal enhancement strategies, including a magnetic bead-linked enzyme-linked immune system catalyzing the production of ascorbic acid from the substrate and a piezoelectric-assisted enhancement strategy, were used for sensitive detection of the analyte to be tested in human body fluids. Unlike the electron transfer mechanism in heterojunctions, piezoelectric semiconductors promote the transfer of electrons and holes by generating piezoelectric potentials in the ultrasonic field, thus contributing to the performance of the PEC testbed. Under optimized conditions, the test platform achieves good correspondence for PSA at 0.02-40 ng mL-1. Impressively, the test devices are comparable to or even superior to gold standard ELISA kits in terms of cost approval and batch testing. This research demonstrates the potential of piezoelectric semiconductors for POC applications in revolutionary PECs and offers innovative thoughts for the development of new PEC bioanalytical components.
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Técnicas Biossensoriais , Técnicas Eletroquímicas , Humanos , Imunoensaio , Limite de Detecção , Masculino , Sistemas Automatizados de Assistência Junto ao Leito , SemicondutoresRESUMO
Functional photothermal nanomaterials have gained widespread attention in the field of precise cancer therapy and early disease diagnosis due to their unique photothermal conversion properties. However, the relatively narrow temperature response range and the outputable accuracy of commercial thermometers limit the accurate detection of biomarkers. Herein, we designed a liposome-embedded Cu2-xAgxS amplification-based photothermal sensor for the accurate determination of cardiac troponin I (cTnI) in health monitoring and point-of-care testing (POCT). The combinable 3D-printing detecting device monitored and visualized target signal changes in the testing system under the excitation of near-infrared (NIR) light, which was recorded and evaluated for possible pathogenicity by a smartphone. Notably, we predicted the potentially efficient thermal conversion efficiency of Cu2-xAgxS from the structure and charge density distribution, calculated by the first-principles and density functional theory (DFT), which provided a theoretical basis for the construction of novel photothermal materials, and the experimental results proved the correctness of the theoretical projections. Under optimal conditions, the photothermal immunoassay showed a dynamic linear range of 0.02-10 ng mL-1 with a detection limit of 11.2 pg mL-1. This work instructively introduces promising theoretical research and provides new insights for the development of sensitive portable photothermal biosensors.
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Lipossomos , Nanopartículas Metálicas , Nanopartículas , Cobre , Imunoensaio/métodos , Limite de Detecção , Lipossomos/química , Nanopartículas/química , Compostos de Prata , Troponina IRESUMO
INTRODUCTION: The lateral parabrachial nucleus (LPBN) is considered to be a brain site of the pyrogenic action of prostaglandin (PG) E2 outside of the preoptic area. Yet, the role of the LPBN in fever following a systemic immune challenge remains poorly understood. METHODS: We examined the expression of cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1) in the LPBN after the intraperitoneal injection of lipopolysaccharide (LPS). We investigated the effects of LPBN NS-398 (COX-2 inhibitor) on LPS-induced fever, the effects of direct LPBN PGE2 administration on the energy expenditure (EE), brown adipose tissue (BAT) thermogenesis, neck muscle electromyographic activity and tail temperature, and the effects of PGE2 on the spontaneous firing activity and thermosensitivity of in vitro LPBN neurons in a brain slice. RESULTS: The COX-2 and mPGES-1 enzymes were upregulated at both mRNA and protein levels. The microinjection of NS-398 in the LPBN attenuated the LPS-induced fever. Direct PGE2 administration in the LPBN resulted in a febrile response by a coordinated response of increased EE, BAT thermogenesis, shivering, and possibly decreased heat loss through the tail. The LPBN neurons showed a clear anatomical distinction in the firing rate response to PGE2, with the majority of PGE2-excited or -inhibited neurons being located in the external lateral or dorsal subnucleus of the LPBN, respectively. However, neither the firing rate nor the thermal coefficient response to PGE2 showed any difference between warm-sensitive, cold-sensitive, and temperature-insensitive neurons in the LPBN. CONCLUSIONS: PGE2 synthesized in the LPBN was at least partially involved in LPS-induced fever via its different modulations of the firing rate of neurons in different LPBN subnuclei.
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Dinoprostona , Núcleos Parabraquiais , Animais , Regulação da Temperatura Corporal , Dinoprostona/metabolismo , Dinoprostona/farmacologia , Lipopolissacarídeos/toxicidade , Núcleos Parabraquiais/metabolismo , Área Pré-Óptica/metabolismo , RatosRESUMO
Application of zero-valent iron (ZVI) has become one of the most promising innovative technologies for the remediation of environmental pollutants. However, ZVI may suffer from the low intrinsic reactivity toward refractory pollutants, which seriously restricts its practical application in fields. Therefore, strategies have been developing to enhance the reactivity of ZVI. Until now, the most commonly used strategies include pretreatment of ZVI, synthesis of highly-active ZVI-based materials and additional auxiliary measures. In this review, a systematic and comprehensive summary of these commonly used strategies has been conducted for the following purposes: (1) to understand the fundamental mechanisms of the selected approaches; (2) to point out their advantages and shortcomings; (3) to illustrate the main problems of their large-scale application; (4) to forecast the future trend of developing ZVI technologies. Overall, this review is devoted to providing a fundamental understanding on the mechanism for enhancing the reactivity of ZVI and facilitating the practical application of ZVI technologies in fields.
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Recuperação e Remediação Ambiental , Poluentes Químicos da Água , FerroRESUMO
BACKGROUND: According to epidemiological studies, gingivitis is a common disease. However, its morbidity, considerably varies among individual. This study aimed to investigate the epidemiological characteristics of gingivitis, including prevalence, severity, intraoral distribution, and associated risk factors, in children aged 6-12 years in Jinzhou, China. METHODS: A multistage, whole-group, randomized sample of 2880 children aged 6-12 years in Jinzhou City, China, was selected and clinically examined. Each selected child completed a questionnaire on sociodemographic factors and oral health behaviors in cooperation with the investigator and teacher. Gingival bleeding refers to the bleeding of 10% or more teeth under the condition of ingivitis. Gingivitis was further categorized into localized gingivitis (30% ≥ number of teeth positive for gingival bleeding ≥ 10%) and generalized gingivitis (number of positive for gingival bleeding > 30%). The score of gingival bleeding was recorded using the Gingival Index. RESULTS: The prevalence of gingivitis in children aged 6-12 years in Jinzhou was 28.58%, including 701 cases of localized gingivitis (24.3%) and 122 cases of generalized gingivitis (4.2%). There were 429 cases (28.3%) of gingivitis in males and 394 cases (28.9%) in females, with no statistically significant difference in prevalence between males and females (P > 0.05). Chi-square tests and binary logistic regression analysis showed that aging, dental calculus, plaque, and dental crowding were significantly associated with a high prevalence of gingivitis. CONCLUSIONS: Our study showed that dental calculus, large amount dental plaque, poor oral health behavior, and oral health awareness are associated with the prevalence of gingivitis and maintaining children's oral health requires professional guidance and regular preventive care.
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Cálculos Dentários , Gengivite , Masculino , Feminino , Criança , Humanos , Cálculos Dentários/epidemiologia , Prevalência , Gengivite/epidemiologia , Gengivite/prevenção & controle , Saúde Bucal , Hemorragia Gengival/epidemiologia , Fatores de Risco , Índice de Placa DentáriaRESUMO
Early diagnosis of cancers relies on the sensitive detection of specific biomarkers, but most of the current testing methods are inaccessible to home healthcare due to cumbersome steps, prolonged testing time, and utilization of toxic and hazardous substances. Herein, we developed a portable self-powered photoelectrochemical (PEC) sensing platform for rapid detection of prostate-specific antigen (PSA, as a model disease-related protein) by integrating a self-powered photoelectric signal output system catalyzed with chemiluminescence-functionalized Au nanoparticles (AuNPs) and a phosphomolybdic acid (PMA)-based photochromic visualization platform. TiO2-g-C3N4-PMA photosensitive materials were first synthesized and functionalized on a sensor chip. The sensor consisted of filter paper modified with a photocatalytic material and a regional laser-etched FTO electrode as an alternative to a conventional PEC sensor with a glass-based electrode. The targeting system involved a monoclonal anti-PSA capture antibody-functionalized Fe3O4 magnetic bead (mAb1-MB) and a polyclonal anti-PSA antibody (pAb2)-N-(4-aminobutyl)-N-ethylisoluminol-AuNP (ABEI-AuNP). Based on the signal intensity of the chemiluminescent system, the photochromic device color changed from light yellow to heteropoly blue through the PMA photoelectric materials integrated into the electrode for visualization of the signal output. In addition, the electrical signal in the PEC system was amplified by a sandwich-type capacitor and readout on a handheld digital multimeter. Under optimum conditions, the sensor exhibited high sensitivity relative to PSA in the range of 0.01-50 ng mL-1 with a low detection limit of 6.25 pg mL-1. The flow-through chemiluminescence reactor with a semiautomatic injection device and magnetic separation was avoid of unstable light source intensity inherent in the chemiluminescence process. Therefore, our strategy provides a new horizon for point-of-care analysis and rapid cost-effective clinical diagnosis.
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Luminescência , Nanopartículas Metálicas , Ouro , ImunoensaioRESUMO
Both warm- and cold-sensitive neurons are found in the lateral parabrachial nucleus (LPB), a crucial relay for skin temperature information from the spinal cord to the preoptic area. The aims of this study were to investigate the electrophysiological properties of temperature-sensitive and -insensitive neurons in brain slices, and elucidate the basic mechanisms underlying the thermosensitivity of rat LPB neurons. In warm-sensitive neurons, temperature exerted no significant effects on resting membrane potential (RMP), threshold potential, and amplitude of the afterhyperpolarizing potential. However, warming significantly increased the prepotential rates of depolarization and the inactivation rates of potassium A current (IA) in warm-sensitive neurons, which in turn shortened their interspike interval and elevated the firing rate. In contrast, temperature had no significant effects on the depolarizing prepotentials and inactivation rate of IA in temperature-insensitive neurons. Besides, in cold-sensitive neurons, cooling and warming produced membrane depolarization and hyperpolarization, respectively, and there was a strong correlation between firing rate and membrane potential thermosensitivity. Nevertheless, temperature exhibited no significant effect on the depolarizing prepotential of cold-sensitive neurons. These results suggest that LPB neuronal warm sensitivity may reside in the temperature-dependent prepotentials and IA, while neuronal cold sensitivity might be mainly due to heat-induced changes in RMP.
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Temperatura Baixa , Potenciais da Membrana , Neurônios/fisiologia , Núcleos Parabraquiais/fisiologia , Animais , Masculino , Núcleos Parabraquiais/citologia , Potássio/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Allogeneic haematopoietic stem cell transplantation (HSCT) is the only available curative therapy for patients with thalassaemia major. With the progress in human leucocyte antigen (HLA) antigen typing technology and supportive care, the outcomes of thalassaemia major have greatly improved in recent years, even in high-risk patients. However, the problem of finding a suitable donor is still a major obstacle to curing these patients. In recent decades, the lack of available HSCT donors has led to the increased use of haploidentical donors (HDs) for HSCT in haematological malignancies. Recently, we explored the effect of HD HSCT to eight children with thalassaemia major based on the FBCA conditioning regimen (fludarabine, busulphan, cyclophosphamide, antithymocyte globulin), which is usually used in leukaemia patients receiving haploidentical HSCT in our centre. So far, all of the transplanted patients have a stable engraftment and are transfusion independent in daily life. This encouraging result has revised our previous conception about haploidentical HCST for thalassaemia major and strongly suggests that HD HSCT is a feasible and safe method for thalassaemia major patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante , Talassemia beta/terapia , Adulto , Aloenxertos , Soro Antilinfocitário/administração & dosagem , Bussulfano/administração & dosagem , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Masculino , Vidarabina/administração & dosagem , Vidarabina/análogos & derivadosRESUMO
This study explores the performance of Sentinel-2A Multispectral Instrument (MSI) imagery for extracting urban impervious surface using a modified linear spectral mixture analysis (MLSMA) method. Sentinel-2A MSI provided 10 m red, green, blue, and near-infrared spectral bands, and 20 m shortwave infrared spectral bands, which were used to extract impervious surfaces. We aimed to extract urban impervious surfaces at a spatial resolution of 10 m in the main urban area of Guangzhou, China. In MLSMA, a built-up image was first extracted from the normalized difference built-up index (NDBI) using the Otsu's method; the high-albedo, low-albedo, vegetation, and soil fractions were then estimated using conventional linear spectral mixture analysis (LSMA). The LSMA results were post-processed to extract high-precision impervious surface, vegetation, and soil fractions by integrating the built-up image and the normalized difference vegetation index (NDVI). The performance of MLSMA was evaluated using Landsat 8 Operational Land Imager (OLI) imagery. Experimental results revealed that MLSMA can extract the high-precision impervious surface fraction at 10 m with Sentinel-2A imagery. The 10 m impervious surface map of Sentinel-2A is capable of recovering more detail than the 30 m map of Landsat 8. In the Sentinel-2A impervious surface map, continuous roads and the boundaries of buildings in urban environments were clearly identified.
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It is well known that sympathetic nerve activity innervating brown adipose tissue (BAT sympathetic nerve activity) plays an important role in BAT thermogenesis. We have found that peripheral administration of arginine vasopressin (AVP) induced hypothermia by reduced thermogenesis in BAT. However, little is known about AVP-induced hypothermic response and its relationship with BAT sympathetic nerve activity. Because increases in baroreceptor inputs inhibit peripheral sympathetic nervous activity, we hypothesized that AVP-induced hypothermia is related to baroreceptor reflex suppression of BAT sympathetic nerve activity. To test this hypothesis, Male Sprague-Dawley rats were subjected to sinoaortic denervation or sham denervation, and implanted with radiotelemetry transmitters to assess the effects of peripheral administration of AVP on BAT sympathetic nerve activity, core and BAT temperatures. In sham-operated rats, an intraperitoneal (i.p.) injection of 10µg/kg AVP led to a significant decrease in core and BAT temperatures. However, sinoaortic denervation significantly reduced the fall of core and BAT temperatures induced by AVP, compared with levels in sham-operated rats. AVP (10µg/kg i.p.) rapidly decreased BAT sympathetic nerve activity in control and sham-operated rats, with the greatest levels of suppression occurring at 35min and these lowest levels attained were with 30.6% and 29.24%, respectively. Furthermore, we found that sinoaortic denervation attenuated the suppressive effects of AVP (10µg/kg i.p.) on BAT sympathetic nerve activity. The greatest level of suppression was only 20.8% occurring at 35min after AVP. Therefore, these results indicate that the hypothermic effects of peripheral administration of AVP are partially mediated by the arterial baroreceptor reflex suppression of BAT sympathetic nerve activity and BAT thermogenesis.
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Tecido Adiposo Marrom/inervação , Sistema Nervoso Simpático/fisiologia , Tecido Adiposo Marrom/fisiologia , Animais , Denervação , Hipotermia Induzida , Masculino , Ratos , Ratos Sprague-Dawley , Sistema Nervoso Simpático/cirurgia , VasopressinasRESUMO
BACKGROUND: The prognostic value of the telomerase reverse transcriptase (TERT) promoter mutation, resulting in poor clinical outcomes of papillary thyroid carcinoma (PTC), has been generally confirmed. To data, there is no high-level evidence approving the association of TERT promoter mutation and aggressive clinical behaviours in PTC. To systematically evaluate it, a systematic review and meta-analysis of the published literatures were carried out. METHODS: We conducted a systematic search in PubMed, EMBASE, OVID and Web of Science databases for relevant studies. We selected all the studies that reported clinicopathological features of PTC patients with information available on TERT promoter mutation status. Individual study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, as were Mantel-Haenszel pooled odds ratios for the combined studies. RESULTS: Eight eligible trials involved 2035 patients were included in the analysis. The average prevalence of the TERT promoter mutation was 10·32%. Compared with the wild-type TERT promoter gene, the TERT promoter mutation was associated with male gender, lymph node metastasis, extrathyroidal extension, distant metastasis, advanced TNM stage III/IV, poor clinical outcome (persistence or recurrence) and mortality. The associations were generally consistent across the different study populations. CONCLUSIONS: Thus, our findings from this large meta-analysis definitively demonstrate that TERT promoter mutation-positive PTC is more likely to manifest with aggressive clinicopathological characteristics. In appropriate clinical settings, testing for the TERT promoter mutation is likely to be useful in assisting the risk stratification and management of PTC.
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Carcinoma/genética , Telomerase/genética , Neoplasias da Glândula Tireoide/genética , Carcinoma/diagnóstico , Carcinoma Papilar , Humanos , Mutação , Prognóstico , Regiões Promotoras Genéticas , Medição de Risco , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/diagnósticoRESUMO
The morphology evolution mechanism of polystyrene (PS)/poly (vinyl methyl ether) (PVME) blend thin films with different PS molecular weights (Mw) was studied. It was found that the morphology evolution was closely related to the molecular weight asymmetry between PS and PVME. In the film where Mw(PS) ≈ Mw(PVME), dewetting happened at the interface between the bottom layer and substrate after SD phase separation. While in the film where Mw(PS) >> Mw(PVME), dewetting happened at the interface between the middle PS/PVME blend layer and bottom PVME layer near the substrate prior to phase separation. The different sequences of phase separation and dewetting and different interface for dewetting occurrence were studied by regarding the competitive effects of viscoelasticity contrast between polymer components and preferential wetting between PVME and the substrate. The viscoelastic nature of the PS component played a crucial role in the sequence of phase separation and dewetting.
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OBJECTIVE: To analyze the relationship between cytomegalovirus (CMV) reactivation and leukemia relapse after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). METHODS: A total of 61 patients diagnosed as hematological malignancies undergoing haplo-HSCT were analyzed retrospectively in our center. RESULTS: In the cohort, 36 patients had CMV reactivation after haplo-HSCT. The 100-day cumulative incidence of CMV reactivation was 59%. Compared with that in patients without CMV reactivation after transplantation, the incidence of leukemia relapse was lower in patients with CMV reactivation (16.9% vs 40.0%, P=0.034). The correlation of CMV reactivation and decreased relapse rate was only found in patients with acute myeloid leukemia (P=0.019). In multivariate analysis, relapsed disease status before transplant was a significant negative predictor of overall survival (OS) and relapse after transplant (RR was 2.866 and 3.331 respectively). CMV reactivation after transplant had a protective effect on disease relapse (RR=0.300, P=0.047). CONCLUSIONS: The rate of CMV reactivation after haplo-HSCT is high. CMV reactivation may reduce risk of relapse in patients diagnosed as acute myeloid leukemia undergoing haplo-HSCT. However, CMV reactivation is one of the important predictors of non-relapse death after transplant, active anti-viral treatment is still needed.
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Infecções por Citomegalovirus/patologia , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Ativação Viral , Antivirais/uso terapêutico , Citomegalovirus , Infecções por Citomegalovirus/tratamento farmacológico , Humanos , Incidência , Leucemia Mieloide Aguda/virologia , Recidiva , Estudos Retrospectivos , Fatores de Risco , Transplante HomólogoRESUMO
OBJECTIVE: To determine the contribution of the OCT-4 to the pathogenesis of leukemia. METHODS: Bone marrow (BM) samples obtained from 72 patients with leukemia, and 18 normal healthy subjects were assayed for their OCT-4 expression using both flow cytometry and RT-PCR. RESULTS: OCT-4 expression in BM nucleated cells of acute leukemia patients (n=33) was significantly higher than that of complete remission and chronic phase leukemia patients (n=39, p<0.001) and healthy donors (n=18, p<0.001). OCT-4 expression had a significant positive relation with CD34 expression (n=43, r=0.721, p<0.001) and the proportion of naive cells (n=60, r=0.687, p<0.001). In addition, the results of QRT-PCR detection showed that the OCT-4A had increased expression in BM nucleated cells in the patients with acute leukemia (n=33, median 16.585, range 0.38-169.62) compared to that in leukemia patients with chronic phase and in complete remission (n=39, median 3.34, range 0.04-44.49, p<0.001) and that of normal controls (n=18, median 2.89, range 0.18-16.23, p<0.001). CONCLUSION: OCT-4A expression was significantly increased in the BM nucleated cells of patients with acute leukemia, indicating that OCT-4A may play an important role in the pathogenesis of leukemia and may serve as a molecular target for the development of novel diagnostic and treatment strategies in leukemia.
Assuntos
Células da Medula Óssea/metabolismo , Regulação Leucêmica da Expressão Gênica , Leucemia/metabolismo , Proteínas de Neoplasias/biossíntese , Fator 3 de Transcrição de Octâmero/biossíntese , Doença Aguda , Adolescente , Adulto , Idoso , Antígenos CD34/biossíntese , Células da Medula Óssea/patologia , Feminino , Humanos , Leucemia/diagnóstico , Leucemia/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Osteochondroma is rarely seen in the facial region, especially around the condyle. Here, we report a case of condylar osteochondroma, aiming to assist the diagnosis and treatment of the tumor. METHODS: A case of osteochondroma of the left mandibular condyle in a 49-year-old man was presented. Medical records with x-ray, computed tomographic scan, and bone scan of histologically proven osteochondroma of mandibular condyle were obtained. RESULTS: The patient underwent a surgical resection and had fewer functional changes as well as less dysfunction of the temporomandibular joint. CONCLUSIONS: The current study highlights the fact that, despite its rarity in the mandibular condyle, surgical resection is an effective treatment method. The decision, however, depends on how much swing of the mandible is required after surgery for correction of asymmetry and occlusion.