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Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease. Cellular and systemic lipid metabolism plays a significant role in the regulation of immune cell activities. However, the role of lipoprotein lipids and apolipoproteins in ITP remains elusive. The automatic biochemistry analyser was used to measure the levels of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-I (apoA-I), apoB, apoE and lipoprotein a [LP(a)]. Genetic variants strongly associated with circulating lipoprotein lipids and apolipoproteins (LDL-C, apoB, TG, HDL-C and apoA-I) were extracted to perform Mendelian randomization (MR) analyses. Finally, drug-target MR and passive ITP mice model was used to investigate the potential druggable targets of ITP. Levels of HDL-C, apoA-I, decreased and LP(a) increased in ITP patients compared with healthy controls. Low HDL-C was causally associated with ITP susceptibility. Through drug-target MR and animal modelling, ABCA1 was identified as a potential target to design drugs for ITP. Our study found that lipid metabolism is related to ITP. The causative association between HDL-C and the risk of ITP was also established. The study provided new evidence of the aetiology of ITP. ABCA1 might be a potential drug target for ITP.
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Apolipoproteína A-I , Púrpura Trombocitopênica Idiopática , Animais , Camundongos , Humanos , Apolipoproteína A-I/genética , LDL-Colesterol , Lipídeos , Análise da Randomização Mendeliana , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/genética , Apolipoproteínas/genética , Triglicerídeos , HDL-ColesterolRESUMO
Although multiple forms of dimers have been described for GPCR, their dynamics and function are still controversially discussed field. Fluorescence microscopy allows GPCR to be imaged within their native context; however, a key challenge is to site-specifically incorporate reporter moieties that can produce high-quality signals upon formation of GPCR dimers. To this end, we propose a supramolecular sensor approach to detect agonist-induced dimer formation of µ-opioid receptors (µORs) at the surface of intact cells. With the macrocyclic host cucurbit[7]uril and its guest hemicyanine dye tethered to aptamer strands directed against the histidine residues, the sensing module is assembled by host-guest complexation once the histidine-tagged µORs dimerize and bring the discrete supramolecular units into close proximity. With the enhanced sensitivity attributed by the "turn-on" fluorescence emission and high specificity afforded by the intermolecular recognition, in situ visualization of dynamic GPCR dimerization was realized with high precision, thereby validating the supramolecular sensing entity as a sophisticated and versatile strategy to investigate GPCR dimers, which represent an obvious therapeutic target.
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Hidrocarbonetos Aromáticos com Pontes , Carbocianinas , Corantes Fluorescentes , Corantes Fluorescentes/química , Hidrocarbonetos Aromáticos com Pontes/química , Dimerização , HistidinaRESUMO
BACKGROUND: Aplastic anemia (AA) is a kind of bone marrow failure (BMF) characterized by pancytopenia with hypoplasia/aplasia of bone marrow. Immunosuppressive therapy and bone marrow transplantation are effective methods to treat severe aplastic anemia. However, the efficacy is limited by complications and the availability of suitable donors. This study aimed to determine whether any circulating druggable protein levels may have causal effects on AA and provide potential novel drug targets for AA. METHODS: Genetic variants strongly associated with circulating druggable protein levels to perform Mendelian randomization (MR) analyses were used. The effect of these druggable protein levels on AA risk was measured using the summary statistics from a large-scale proteomic genome-wide association study (GWAS) and FinnGen database ( https://www.finngen.fi/en/access_results ). Multivariable MR analyses were performed to statistically adjust for potential confounders, including platelet counts, reticulocyte counts, neutrophil counts, and proportions of hematopoietic stem cells. RESULTS: The data showed that higher level of circulating IFN-γ levels was causally associated with AA susceptibility. The causal effects of circulating IFN-γ levels on the AA were broadly consistent, when adjusted for platelet counts, reticulocyte counts, neutrophil counts and proportions of hematopoietic stem cells. CONCLUSIONS: High levels of circulating IFN-γ levels might increase the risk of AA and might provide a potential novel target for AA.
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Anemia Aplástica , Estudo de Associação Genômica Ampla , Interferon gama , Análise da Randomização Mendeliana , Proteoma , Anemia Aplástica/genética , Anemia Aplástica/sangue , Humanos , Interferon gama/sangue , Proteoma/análise , Masculino , FemininoRESUMO
LINC00624 is a long noncoding RNA (lncRNA) which was seldom investigated before. The goal of our study is to clarify the expression and underlying network of LINC00624 in hepatocellular carcinoma (HCC). Here, both HCC and normal living cell lines were employed. Real-time quantitative PCR and western blot were used to determine the pattern of genes and proteins. Colony formation, flow cytometry and western blot tests were used to determine cell proliferation and apoptosis, respectively. Dual luciferase was used to verify molecule-molecule interactions. LINC00624 expression was increased in HCC cell lines and miR-342-3p was decreased. Elimination of LINC00624 increased proliferation while decreasing cell apoptosis. LINC00624 acted as a molecular sponge for miR-342-3p, hence facilitating DNAJC5 expression. Functional tests demonstrated that miR-342-3p suppression could reverse the effect of LINC00624 silence and overexpression of DNAJC5 significantly mitigated the biological consequences of miR-342-3p. These finding demonstrated that LINC00624 aggravated HCC progression by modulating proliferation and apoptosis via targeting miR-342-3p/DNAJC5 axis. These data support that inhibition of LINC00624 may a potential treatment strategies of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Apoptose , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não CodificanteRESUMO
BACKGROUND: Schwannomas are the most common intrathoracic neurogenic tumors. In the past, they were often treated by traditional open surgery. Video-assisted thoracic surgery (VATS) has also been used for some large tumors. Recently, minimally invasive posterior neurosurgical technique provides a new option for some of these tumors. METHOD: Here, we describe the specific steps involved in the O-arm guided minimally invasive removal of intrathoracic epidural schwannoma, as well as its advantages and limitations. CONCLUSION: O-arm guided minimally invasive resection of intrathoracic epidural schwannoma is safe and effective and causes little damage.
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Neurilemoma , Cirurgia Assistida por Computador , Humanos , Imageamento Tridimensional , Tomografia Computadorizada por Raios X , Neurilemoma/diagnóstico por imagem , Neurilemoma/cirurgia , Procedimentos NeurocirúrgicosRESUMO
Investigating the dynamic response patterns and failure modes of concrete gravity dams subjected to strong earthquakes is a pivotal area of research for addressing seismic safety concerns associated with gravity dam structures. Dynamic shaking table testing has proven to be a robust methodology for exploring the dynamic characteristics and failure modes of gravity dams. This paper details the dynamic test conducted on a gravity dam model on a shaking table. The emulation concrete material, featuring high density, low dynamic elastic modulus, and appropriate strength, was meticulously designed and fabricated. Integrating the shaking table conditions with the model material, a comprehensive gravity dam shaking table model test was devised to capture the dynamic response of the model under various dynamic loads. Multiple operational conditions were carefully selected for in-depth analysis. Leveraging the dynamic strain responses, the progression of damage in the gravity dam model under these diverse conditions was thoroughly examined. Subsequently, the recorded acceleration responses were utilized for identifying dynamic characteristic parameters, including the acceleration amplification factor in the time domain, acceleration response spectrum characteristics in the frequency domain, and modal parameters reflecting the inherent characteristics of the structure. To gain a comprehensive understanding, a comparative analysis was performed by aligning the observed damage development with the identified dynamic characteristic parameters, and the sensitivity of these identified parameters to different levels of damage was discussed. The findings of this study not only offer valuable insights for conducting and scrutinizing shaking table experiments on gravity dams but also serve as crucial supporting material for identifying structural dynamic characteristic parameters and validating damage diagnosis methods for gravity dam structures.
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Modal parameter estimation is crucial in vibration-based damage detection and deserves increased attention and investigation. Concrete arch dams are prone to damage during severe seismic events, leading to alterations in their structural dynamic characteristics and modal parameters, which exhibit specific time-varying properties. This highlights the significance of investigating the evolution of their modal parameters and ensuring their accurate identification. To effectively accomplish the recursive estimation of modal parameters for arch dams, an adaptive recursive subspace (ARS) method with variable forgetting factors was proposed in this study. In the ARS method, the variable forgetting factors were adaptively updated by assessing the change rate of the spatial Euclidean distance of adjacent modal frequency identification values. A numerical simulation of a concrete arch dam under seismic loading was conducted by using ABAQUS software, in which a concrete damaged plasticity (CDP) model was used to simulate the dam body's constitutive relation, allowing for the assessment of damage development under seismic loading. Utilizing the dynamic responses obtained from the numerical simulation, the ARS method was implemented for the modal parameter recursive estimation of the arch dam. The identification results revealed a decreasing trend in the frequencies of the four initial modes of the arch dam: from an undamaged state characterized by frequencies of 0.910, 1.166, 1.871, and 2.161 Hz to values of 0.895, 1.134, 1.842, and 2.134 Hz, respectively. Concurrently, increases in the damping ratios of these modes were observed, transitioning from 4.44%, 4.28%, 5.42%, and 5.56% to 4.98%, 4.91%, 6.61%, and 6.85%%, respectively. The correlation of the identification results with damage progression validated the effectiveness of the ARS method. This study's outcomes have substantial theoretical and practical importance, facilitating the immediate comprehension of the dynamic characteristics and operational states of concrete arch dam structures.
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Neurotransmitter exocytosis of living cells plays a vital role in neuroscience. However, the available amperometric technique with carbon fiber electrodes typically measures exocytotic events from one cell during one procedure, which requires professional operations and takes time to produce statistical results of multiple cells. Here, we develop a functionally collaborative nanostructure to directly measure the neurotransmitter dopamine (DA) exocytosis from living rat pheochromocytoma (PC12) cells. The functionally collaborative nanostructure is constructed of metal-organic framework (MOF)-on-nanowires-on-graphene oxide, which is highly sensitive to DA molecules and enables direct detection of neurotransmitter exocytosis. Using the microsensor, the exocytosis from PC12 cells pretreated with the desired drugs (e.g., anticoronavirus drug, antiflu drug, or anti-inflammatory drug) has been successfully measured. Our achievements demonstrate the feasibility of the functionally collaborative nanostructure in the real-time detection of exocytosis and the potential applicability in the highly efficient assessment of the modulation effects of medications on exocytosis.
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Dopamina , Nanoestruturas , Animais , Ratos , Eletrodos , Exocitose/fisiologia , NeurotransmissoresRESUMO
Calcination plays a vital role during material preparation. However, the calcination conditions have often been determined empirically or have been based on trial and error. Herein we present a cooperative characterization approach to optimize calcination conditions by gas-cell in situ TEM in collaboration with microcantilever-based thermogravimetric analysis (cantilever-TGA) techniques. The morphological evolution of precursors under atmospheric conditions is observed with in situ TEM, and the right calcination temperature is provided by cantilever-TGA. The proposed approach successfully optimizes the calcination conditions of fragile MnO2 nanowire precursors with multiple valence products. The cantilever-TGA shows that a calcination temperature above 560 °C is required to transform the MnO2 precursor to Mn3O4 under an N2 atmosphere, but the in situ TEM indicates that the nanowire structure is destroyed within only 30 min under calcination conditions. Our method further suggests that heating the precursor at 400 °C using an H2-containing atmosphere can produce Mn3O4 nanowires with good electrical properties.
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BACKGROUND: How to improve efficacy and reduce side effects in treating recurrent esophageal cancer by applying the second course of radiotherapy alone and its combination with chemotherapy has been attracting broad research interest. OBJECTIVE: This review paper aims to systematically evaluate efficacy and side effects of applying the second course of anterograde radiotherapy alone and its combination with chemotherapy in treating recurrent esophageal cancer. METHODS: First, the relevant research papers are retrieved from PubMed, CNKI and Wanfang databases. Next, Redman 5.3 software is used to calculate the relative risk and 95% confidence interval to evaluate the efficacy and adverse reactions of applying the single-stage radiotherapy with and without combining single/multi dose chemotherapy to treat recurrent esophageal cancer. Then, a meta data analysis is applied to examine the effectiveness and side effects of radiation alone and re-course radiotherapy plus chemotherapy in treating esophageal cancer recurrence after the first radiotherapy. RESULTS: Fifteen papers are retrieved, which included 956 patients. Among them, 476 patients received radiotherapy combined with single drug/multi drug chemotherapy (observation) and others received only radiotherapy (control). Data analysis results show that the incidence of radiation induced lung injury and bone marrow suppression is high in the observation group. Subgroup analysis also shows the higher effective rate or one-year overall survival rate of patients treated with the second course radiotherapy combined with single drug chemotherapy. CONCLUSION: The meta-analysis result demonstrates that combining the second course of radiotherapy with single-drug chemotherapy has advantages in treating recurrent esophageal cancer with the manageable side effects. However, due to insufficient data, it is not possible to conduct the further subgroup analysis comparing the side effects of restorative radiation with the combined chemotherapy using between a single drug and multiple drugs.
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Neoplasias Esofágicas , Recidiva Local de Neoplasia , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/radioterapia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapiaRESUMO
Alkaline zinc-ferricyanide flow batteries are efficiency and economical as energy storage solutions. However, they suffer from low energy density and short calendar life. The strongly alkaline conditions (3â mol L-1 OH-) reduce the solubility of ferri/ferro-cyanide (normally only 0.4â mol L-1 at 25 °C) and induce the formation of zinc dendrites at the anode. Here, we report a new zinc-ferricyanide flow battery based on a mild alkalescent (pHâ 12) electrolyte. Using a chelating agent to rearrange ferri/ferro-cyanide ion-solvent interactions and improve salt dissociation, we increased the solubility of ferri/ferro-cyanide to 1.7â mol L-1 and prevented zinc dendrites. Our battery has an energy density of ~74â Wh L-1 catholyte at 60 °C and remains stable for 1800â cycles (1800â hours) at 0 °C and for >1400â cycles (2300â hours) at 25 °C. An alkalescent zinc-ferricyanide cell stack built using this alkalescent electrolyte stably delivers 608â W of power for ~40â days.
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Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia. This bibliometric analysis was applied to identify the characteristics of global scientific output, the hotspots, and frontiers of ITP over the past 10 years. We retrieved publications from 2011 to 2021 from the Web of Science Core Collection (WoSCC). Bibliometrix package, VOSviewer, and Citespace were used to analyse and visualize the trend, distribution, and hotspots of research on ITP. Altogether, there were 2084 papers, written by 9080 authors from 410 organizations in 70 countries/regions, published in 456 journals with 37 160 co-cited references. In the last decades, the most productive journal was British Journal of Haematology, China was the most productive country. and the most cited journal was Blood. Shandong University was the most productive institution in the field of ITP. NEUNERT C, 2011, BLOOD, CHENG G, 2011, LANCET, and PATEL VL, 2012, BLOOD were the top three most cited documents. "Thrombopoietin receptor agonist", "regulatory T cell" and "sialic acid" were three hotspots of the last decade. And "immature platelet fraction", "Th17", and "fostamatinib" would be research frontiers in the feature. The present study provided a novel insight for future research directions and scientific decision-making.
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Púrpura Trombocitopênica Idiopática , Humanos , Bibliometria , Plaquetas , China , Ácido N-AcetilneuramínicoRESUMO
Immune thrombocytopenia (ITP) is an autoimmune haemorrhagic disease, in which the overactivation of T cells is crucial in the pathogenesis. Atorvastatin (AT), a lipid-lowering medicine, has shown promising immunomodulatory effects in certain inflammatory conditions. However, the immunoregulatory role of AT in ITP remains elusive. To investigate the effect of AT in the treatment of ITP, cluster of differentiation 4 (CD4)+ T cells were isolated from patients with ITP and cultured with different dosages of AT. We found that AT significantly inhibited cell proliferation, led to cell cycle arrest, induced apoptosis, and repressed the activation of CD4+ T cells in vitro. ITP murine models were then established, and results showed that AT treatment led to faster recovery of the platelet count to normal and exhibited comparable immunomodulatory function. Furthermore, we found the phosphorylation of mammalian target of rapamycin (mTOR), protein kinase B (AKT) and extracellular signal-regulated kinase (ERK), as well as activation of rat sarcoma virus (RAS) were all reduced dramatically after AT treatment in vitro. In conclusion, our present study demonstrated that AT could reinstate the functions of CD4+ T cells by inhibiting the excessive activation, proliferation, and survival of CD4+ T cells in ITP via the RAS/mitogen-activated protein kinase kinase (MEK)/ERK and the mTOR/phosphatidylinositol-3 kinase (PI3K)/AKT pathway. Therefore, we propose that AT could be used as a potential therapeutic option for ITP by restoring the over-activated cellular immunity.
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Linfócitos T CD4-Positivos , Púrpura Trombocitopênica Idiopática , Animais , Camundongos , Atorvastatina/farmacologia , Atorvastatina/uso terapêutico , MAP Quinases Reguladas por Sinal Extracelular , Mamíferos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linfócitos T/metabolismo , Serina-Treonina Quinases TORRESUMO
Metal oxide semiconductor (MOS) thin films are of critical importance to both fundamental research and practical applications of gas sensors. Herein, a high-performance H2 sensor based on palladium (Pd) and rhodium (Rh) co-functionalized Fe2 O3 films with an ultrathin thickness of 8.9 nm deposited by using atomic layer deposition is reported. The sensor delivers an exceptional response of 105.9 toward 10 ppm H2 at 230 °C, as well as high selectivity, immunity to humidity, and low detection limit (43 ppb), which are superior to the reported MOS sensors. Importantly, the Fe2 O3 film sensor under dynamic H2 detection is for the first time observed by operando transmission electron microscopy, which provides deterministic evidence for structure evolution of MOS during sensing reactions. To further reveal the sensing mechanism, density functional theory calculations are performed to elucidate the sensitization effect of PdRh catalysts. Mechanistic studies suggest that Pd promotes the adsorption and dissociation of H2 to generate PdHx , while Rh promotes the dissociation of oxygen adsorbed on the surface, thereby jointly promoting the redox reactions on the films. A wireless H2 detection system is also successfully demonstrated using the thin film sensors, certifying a great potential of the strategy to practical sensors.
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BACKGROUND: Cyclooxygenase (COX)-2 is a rate-limiting enzyme in the biosynthesis of prostanoids, which is mostly inducible by inflammatory cytokines. The participation of COX-2 in the maturation of megakaryocytes has been reported but barely studied in primary immune thrombocytopenia (ITP). METHODS: The expressions of COX-2 and Caspase-1, Caspase-3 and Caspase-3 p17 subunit in platelets from ITP patients and healthy controls (HC), and the expressions of COX-2 and CD41 in bone marrow (BM) of ITP patients were measured and analyzed for correlations. The effects of COX-2 inhibitor on megakaryopoiesis and thrombopoiesis were assessed by in vitro culture of Meg01 cells and murine BM-derived megakaryocytes and in vivo experiments of passive ITP mice. RESULTS: The expression of COX-2 was decreased and Caspase-1 and Caspase-3 p17 were increased in platelets from ITP patients compared to HC. In platelets from ITP patients, the COX-2 expression was positively correlated with platelet count and negatively correlated to the expression of Caspase-1. In ITP patients BM, the expression of CD41 was positively correlated with the expression of COX-2. COX-2 inhibitor inhibited the count of megakaryocytes and impaired the maturation and platelet production in Meg01 cells and bone marrow-derived megakaryocytes. COX-2 inhibitor aggravated thrombocytopenia and damaged megakaryopoiesis in ITP murine model. CONCLUSION: COX-2 plays a vital role in the physiologic and pathologic conditions of ITP by intervening the survival of platelets and impairing the megakaryopoiesis and thrombopoiesis of megakaryocytes.
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Púrpura Trombocitopênica Idiopática , Trombopoese , Animais , Camundongos , Plaquetas/metabolismo , Caspase 3/metabolismo , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2 , Megacariócitos/metabolismo , Trombopoese/fisiologiaRESUMO
Our previous clinical study showed that low-dose decitabine exhibited sustained responses in nearly half of patients with refractory immune thrombocytopenia (ITP). The long-term efficacy of decitabine in ITP is not likely due to its simple role in increasing platelet production. Whether decitabine has the potential to restore immune tolerance in ITP is unknown. In this study, we analyzed the effect of decitabine on T-cell subpopulations in ITP in vitro and in vivo. We found that low-dose decitabine promoted the generation and differentiation of regulatory T (Treg) cells and augmented their immunosuppressive function. Splenocytes from CD61 knockout mice immunized with CD61+ platelets were transferred into severe combined immunodeficient mouse recipients to induce a murine model of ITP. Low-dose decitabine alleviated thrombocytopenia and restored the balance between Treg and helper T (Th) cells in active ITP mice. Treg deletion and depletion offset the effect of decitabine in restoring CD4+ T-cell subpopulations in ITP mice. For patients who received low-dose decitabine, the quantity and function of Treg cells were substantially improved, whereas Th1 and Th17 cells were suppressed compared with the pretreatment levels. Next-generation RNA-sequencing and cytokine analysis showed that low-dose decitabine rebalanced T-cell homeostasis, decreased proinflammatory cytokines, and downregulated phosphorylated STAT3 in patients with ITP. STAT3 inhibition analysis suggested that low-dose decitabine might restore Treg cells by inhibiting STAT3 activation. In conclusion, our data indicate that the immunomodulatory effect of decitabine provides one possible mechanistic explanation for the sustained response achieved by low-dose decitabine in ITP.
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Plaquetas , Decitabina , Tolerância Imunológica , Fatores Imunológicos , Púrpura Trombocitopênica Idiopática , Recuperação de Função Fisiológica , Linfócitos T Reguladores , Adulto , Idoso , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Plaquetas/imunologia , Decitabina/administração & dosagem , Tolerância Imunológica/efeitos dos fármacos , Fatores Imunológicos/administração & dosagem , Camundongos Knockout , Camundongos SCID , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/imunologia , Púrpura Trombocitopênica Idiopática/patologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Células Th1/imunologia , Células Th1/patologia , Células Th17/imunologia , Células Th17/patologiaRESUMO
Primary immune thrombocytopenia (ITP) is the most common acquired autoimmune bleeding disorder. Abnormally increased levels of High Mobility Group Box 1 (HMGB1) protein associate with thrombocytopenia and therapeutic outcome in ITP. Previous studies proposed that a natural inhibitor of HMGB1, 18ß-glycyrrhetinic acid (18ß-GA), could be used for its anti-inflammatory and immune-modulatory effects, although its ability to correct immune balance in ITP is unclear. In this study, we showed that plasma HMGB1 correlated negatively with platelet counts in ITP patients, and confirmed that 18ß-GA stimulated the production of regulatory T cells (Treg), restored the balance of CD4+ T-cell subsets and enhanced the suppressive function of Treg through blocking the effect on HMGB1 in patients with ITP. HMGB1 short hairpin RNA interference masked the effect of 18ß-GA in Treg of ITP patients. Furthermore, we found that 18ß-GA alleviated thrombocytopenia in mice with ITP. Briefly, anti-CD61 immune-sensitized splenocytes were transferred into severe combined immunodeficient mice to induce a murine model of severe ITP. The proportion of circulating Treg increased significantly, while the level of plasma HMGB1 and serum antiplatelet antibodies decreased significantly in ITP mice along 18ß-GA treatment. In addition, 18ß-GA reduced phagocytic activity of macrophages towards platelets both in ITP patients and ITP mice. These results indicate that 18ß-GA has the potential to restore immune balance in ITP via inhibition of HMGB1 signaling. In short, this study reveals the role of HMGB1 in ITP, which may serve as a potential target for thrombocytopenia therapy.
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Proteína HMGB1 , Púrpura Trombocitopênica Idiopática , Trombocitopenia , Animais , Camundongos , Linfócitos T Reguladores , Proteína HMGB1/genética , Trombocitopenia/genéticaRESUMO
Our understanding of the microstructure of many plant proteins is based on the ancient and conventional methods of alkali extraction and acid precipitation, which generate considerable amounts of NaCl causing salting-out effects and aggregation of their molecules. In this study, monodisperse rice protein (RP) nanoparticles were prepared using cation-exchange resins that release H+ and absorb Na+, thus avoiding the generation of NaCl during neutralization of the alkali extracts. The generated RP nanoparticles of small diameter (20 nm) and excellent uniformity (0.17 polydispersity) quickly diffuse to and stabilize the oil-water interface, producing oil-in-water Pickering emulsions. The emulsifying ability and emulsion stability afforded with these nanoparticles were 17 and 3.5 times higher than those of nanoparticles prepared by conventional alkali extraction and acid precipitation methods, respectively. Furthermore, increased RP nanoparticle concentration created more stable emulsions with smaller droplets and reduced flocculation index vital for practical applications. This study provides a convincing example of how to prepare monodisperse protein nanoparticles that adsorb at a fluid interface, which may find numerous applications in food and cosmetic formulations.
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BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease characterized by increased platelet destruction and impaired thrombopoiesis. The changes in platelet indices depend on the morphology and volume of platelets. Serum lipids have been found to affect platelet formation and activity in certain diseases, thus inducing the corresponding variation of platelet indices. METHODS: Mendelian randomization (MR) analysis was performed based on databases. The clinical data from 457 ITP patients were retrospectively collected and analyzed, including platelet indices, serum lipids, hemorrhages and therapeutic responses. RESULTS: MR analysis showed low high-density-lipoprotein-cholesterol (HDL-C), low apolipoprotein A-1, high triglyceride (TG) and high apolipoprotein B (ApoB) caused high platelet distribution width (PDW); high low-density-lipoprotein-cholesterol (LDL-C) increased mean platelet volume (MPV). In ITP, there were positive correlations between platelet count with TG, PDW with HDL-C and ApoB, and plateletcrit with TG and non-esterified fatty acid, and the correlation had gender differences. Bleeding scores were negatively correlated with cholesterol and LDL-C. LDL-C and homocysteine were risk factors for therapeutic responses. CONCLUSIONS: Serum lipids, especially cholesterol were tightly correlated with platelet indices, hemorrhage and therapeutic effects in ITP patients. These results provide clinical references for the management of serum lipids, and highlight the necessity to further explore the relationship between lipids and pathogenesis of ITP. TRIAL REGISTRATION: No: NCT05095896, October 14, 2021, retrospectively registered.
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OBJECTIVE: To detect the expression level of urinary exosomal lncRNA SNHG16 in patients with bladder cancer and healthy individuals and explore its clinical application value in the diagnosis of bladder cancer. METHODS: Urine samples were collected from 42 patients with bladder cancer and 42 healthy volunteers who visited Lu'an Hospital of Anhui Medical University and the Second Hospital of Tianjin Medical University from January 2020 to December 2022. The expression levels of lncRNA SNHG16 in urinary exosomes of the two groups were detected by RTâqPCR, and their correlation with clinical pathological parameters of bladder cancer patients was analysed. An Receiver Operating Characteristic(ROC) curve was drawn to analyse the diagnostic value of urinary exosomal lncRNA SNHG16 for bladder cancer and compared with urinary cytology. RESULTS: The expression of urinary exosomal lncRNA SNHG16 in patients with bladder cancer was significantly higher (P < 0.05), and the expression level had no correlation with the age, sex, pathological T stage, pathological grade, or tumour size of bladder cancer patients (P > 0.05). The Area Under Curve(AUC) of urinary exosomal lncRNA SNHG16 in diagnosing bladder cancer was 0.791, which was superior to that of urinary cytology (AUC = 0.597). CONCLUSION: Urinary exosomal lncRNA SNHG16 with high expression can serve as a potential diagnostic biological marker for bladder cancer.