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The concept of bio-inspired gradient hierarchies, in which the well-defined MOF nanocrystals serve as active nanodielectrics to create electroactive shell at poly(lactic acid) (PLA) nanofibers, is introduced to promote the surface activity and electroactivity of PLA nanofibrous membranes (NFMs). The strategy enabled significant refinement of PLA nanofibers during coaxial electrospinning (â¼40 % decline of fiber diameter), accompanied by remarkable increase of specific surface area (nearly 1.5 m2/g), porosity (approximately 85 %) and dielectric constants for the bio-inspired gradient PLA (BG-PLA) NFMs. It largely boosted initial electret properties and electrostatic adsorption capability of BG-PLA NFMs, as well as charge regeneration by TENG mechanisms even under high-humidity environment. The BG-PLA NFMs thus featured exceptionally high PM0.3 filtration efficiencies with well-controlled air resistance (94.3 %, 163.4 Pa, 85 L/min), in contrast to the relatively low efficiency of only 80.0 % for normal PLA. During the application evaluation of outdoor air purification, excellent long-term filtering performance was demonstrated for the BG-PLA for up to 4 h (nearly 98.0 %, 53 Pa), whereas normal PLA exhibited a gradually declined filtration efficiency and an increased pressure drop. Moreover, the BG-PLA NFMs of increased electroactivity were ready to generate tribo-output currents as driven by respiratory vibrations, which enabled real-time monitoring of electrophysiological signals. This bio-inspired gradient strategy opens up promising pathways to engender biodegradable nanofibers of high surface activity and electroactivity, which has significant implications for intelligent protective membranes.
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Nanofibras , Poliésteres , Nanofibras/química , Poliésteres/química , Material Particulado/química , Humanos , Poluentes Atmosféricos/química , Filtração , Monitoramento Ambiental/métodosRESUMO
Chikungunya virus, a mosquito-borne virus that causes epidemics, is often misdiagnosed due to symptom similarities with other arboviruses. Here, a portable and integrated nucleic acid-based diagnostic device, which combines reverse transcription-loop-mediated isothermal amplification and lateral-flow detection, was developed. The device is simple to use, precise, equipment-free, and highly sensitive, enabling rapid chikungunya virus identification. The result can be obtained by the naked eye within 40 min. The assay can effectively distinguish chikungunya virus from dengue virus, Japanese encephalitis virus, Zika virus, and yellow fever virus with high specificity and sensitivity as low as 598.46 copies mL-1. It has many benefits for the community screening and monitoring of chikungunya virus in resource-limited areas because of its effectiveness and simplicity. The platform has great potential for the rapid nucleic acid detection of other viruses.
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Strategies for rapid, effective nucleic acid processing hold tremendous significance to the clinical analysis of circulating tumor DNA (ctDNA), a family of important markers indicating tumorigenesis and metastasis. However, traditional techniques remain challenging to achieve efficient DNA enrichment, further bringing about complicated operation and limited detection sensitivity. Here, we developed an ion concentration polarization microplatform that enabled highly rapid, efficient enrichment and purification of ctDNA from a variety of clinical samples, including serum, urine, and feces. The platform demonstrated efficiently separating and enriching ctDNA within 30 s, with a 100-fold improvement over traditional methods. Integrating an on-chip isothermal amplification module, the platform further achieved 100-fold enhanced sensitivity in ctDNA detection, which significantly eliminated false-negative results in the serum or urine samples due to the low abundance of ctDNA. Such a simple-designed platform offers a user-friendly yet powerful diagnosis technique with a wide applicability, ranging from early tumor diagnosis to infection screening.
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DNA Tumoral Circulante , Neoplasias , Ácidos Nucleicos , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , DNA Tumoral Circulante/genética , Carcinogênese , Técnicas de Amplificação de Ácido Nucleico/métodosRESUMO
Despite its importance, the functional heterogeneity surrounding the dynamics of interactions between mycobacterium tuberculosis and human immune cells in determining host immune strength and tuberculosis (TB) outcomes, remains far from understood. This work now describes the development of a new technological platform to elucidate the immune function differences in individuals with TB, integrating single-cell RNA sequencing and cell surface antibody sequencing to provide both genomic and phenotypic information from the same samples. Single-cell analysis of 23 990 peripheral blood mononuclear cells from a new cohort of primary TB patients and healthy controls enables to not only show four distinct immune phenotypes (TB, myeloid, and natural killer (NK) cells), but also determine the dynamic changes in cell population abundance, gene expression, developmental trajectory, transcriptomic regulation, and cell-cell signaling. In doing so, TB-related changes in immune cell functions demonstrate that the immune response is mediated through host T cells, myeloid cells, and NK cells, with TB patients showing decreased naive, cytotoxicity, and memory functions of T cells, rather than their immunoregulatory function. The platform also has the potential to identify new targets for immunotherapeutic treatment strategies to restore T cells from dysfunctional or exhausted states.
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Mycobacterium tuberculosis , Tuberculose , Humanos , Leucócitos Mononucleares , Mycobacterium tuberculosis/fisiologia , Linfócitos T , Células Matadoras NaturaisRESUMO
Biodegradable polylactic acid (PLA) nanofibrous membranes (NFMs) hold great potential to address the increasing airborne particulate matter (PM) and dramatic accumulation of plastic/microplastic pollution. However, the field of PLA NFM-based filters is still in its infancy, frequently dwarfed by the bottlenecks regarding relatively low surface activity, poor electroactivity, and insufficient PM capturing mechanisms. This effort discloses a microwave-assisted approach to minute-level synthesis of dielectric ZIF-8 nanocrystals with high specific surface area (over 1012 m2/g) and ultrasmall size (â¼240 nm), which were intimately anchored onto PLA nanofibers (PLA@ZIF-8) by a combined "electrospinning-electrospray" strategy. This endowed the PLA@ZIF-8 NFMs with largely increased electroactivity in terms of elevated dielectric coefficient (an increase of 202%), surface potential (up to 5.8 kV), and triboelectric properties (output voltage of 30.8 V at 10 N, 0.5 Hz). Given the profound control over morphology and electroactivity, the PLA@ZIF-8 NFMs exhibited efficient filtration of PM0.3 (97.1%, 85 L/min) with a decreased air resistance (592.5 Pa), surpassing that of the pure PLA counterpart (88.4%, 650.9 Pa). This was essentially ascribed to realization of multiple filtration mechanisms for PLA@ZIF-8 NFMs, including enhanced physical interception, polar interactions, and electrostatic adsorption, and the unique self-charging function triggered by airflow vibrations. Moreover, perfect antibacterial performance was achieved for PLA@ZIF-8, showing ultrahigh inhibition rates of 99.9 and 100% against E. coli and S. aureus, respectively. The proposed hierarchical structuring strategy, offering the multifunction integration unattainable with conventional methods, may facilitate the development of biodegradable long-term air filters.
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Nanofibras , Nanofibras/química , Plásticos , Escherichia coli , Staphylococcus aureus , Poliésteres/química , Filtração/métodosRESUMO
High-performance air filtration materials are important for addressing the airborne pollutants. Herein, we propose an unprecedented access to biodegradable poly(lactic acid) (PLA)-based MOFilters with excellent filtering performance and antibacterial activity. The fabrication involved a stepwise in situ growth of zeolitic imidazolate framework-8 (ZIF-8) crystals at the surface of microfibrous PLA membranes, followed by mechanical polarization under high pressure and low temperature (5 MPa, 40 °C) to trigger the ordered alignment of dipoles in PLA chains and ZIF-8. The unique structural features allowed these PLA-based MOFilters to achieve an exceptional combination of excellent tensile properties, high dielectric constant (up to 2.4 F/m), and enhanced surface potential as high as 4 kV. Arising from the remarkable surface activity and electrostatic adsorption effect, a significant increase (from over 12% to nearly 20%) in PM0.3 filtration efficiency was observed for the PLA-based MOFilters compared to that of pure PLA counterparts, with weak relation to the airflow velocities (10-85 L/min). Moreover, the air resistance was controlled at a considerably low level for all the MOFilters, that is, below 183 Pa even at 85 L/min. It is worth noting that distinct antibacterial properties were achieved for the MOFilters, as illustrated by the inhibitive rates of 87 and 100% against Escherichia coli and Staphylococcus aureus, respectively. The proposed concept of PLA-based MOFilters offers unprecedented multifunction integration, which may fuel the development of biodegradable versatile filters with high capturing and antibacterial performances yet desirable manufacturing feasibility.
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This study explored the role of metformin (MET) in regulating the polarization of alveolar macrophages to protect against acute lung injury (ALI) in rats caused by paraquat (PQ) poisoning. The in vivo studies showed that the 35 mg/kg dose of MET increased the survival rate of rats, alleviated pathological damages to the lungs and their systemic inflammation, promoted the reduction of the pro-inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels, and increased the anti-inflammatory factor IL-10 levels in the rat serum. At the same time, the MET intervention decreased the expression of M1 macrophage marker iNOS in the lungs of the PQ-poisoned rats while increasing the M2 macrophage marker, Arg1, expression. In vitro, the concentration of MET > 10 mmol/L affected NR8383 viability adversely and was concentration-dependent; however, no adverse impact on NR8383 viability was observed at MET ≤ 10 mmol/L concentration, resisting the reducing effect of PQ on NR8383 vitality. The PQ-induced NR8383 model with MET intervention showed significantly reduced secretions of IL-6 and TNF-α in NR8383, and lowered expressions of M1 macrophage markers iNOS and CD86. Additionally, MET increased IL-10 secretion and the M2 macrophage markers, Arg1 and Mrcl, expressions. Therefore, we speculate that MET could regulate alveolar macrophage polarization to protect against PQ-poisoning caused ALI.
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OBJECTIVE: This study observes the morphological changes in the enteric nervous system (ENS) - interstitial cells of Cajal (ICC) - smooth muscle cells (SMC) network in sphincter of Oddi dysfunction (SOD) in hypercholesterolemic rabbits following treatment with Shaoyao Gancao decoction (SGD), as well as the apoptosis of the ICC. METHODS: In this study, 48 healthy adult New Zealand rabbits are randomly divided into three groups (n = 16 in each group): the control, the model, and the SGD treatment groups. The hypercholesterolemic rabbit model is established. Hematoxylin and eosin staining, transmission electron microscopy, immunofluorescence, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, immunohistochemistry, Western blot analysis, and reverse transcription-polymerase chain reaction are used to detect the morphological changes in the ENS-ICC-SMC network, the expression of apoptosis-related proteins in the ICC, and to observe the curative effect of SGD after treatment. RESULTS: Compared with the control group, the morphology and the ultrastructure of the SO are destroyed in the model group. In addition, the protein gene product 9.5 (PGP9.5), nitric oxide (NO), the SMCs, and the ICC all significantly decreased while substance P (SP) significantly increased. Compared with the model group, the SO morphology and ultrastructure are repaired in the SGD group. In addition, the PGP9.5, NO, the SMCs, and the ICC significantly increased while SP decreased. In addition, SGD may activate the stem cell factor (SCF)/c-Kit signaling pathway to treat SO dysfunction by up-regulating the expression of c-Kit and SCF. Similarly, this pathway restores SO by up-regulating the expression of Bcl2 and inhibiting cleaved caspase-3, Bax, and the tumor necrosis factor. CONCLUSION: Shaoyao Gancao decoction can promote the recovery of sphincter of Oddi dysfunction in hypercholesterolemic rabbits by protecting the ENS-ICC-SMC network.
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Endoscopic retrograde cholangiopancreatography (ERCP) is the main diagnosis and treatment for biliary and pancreatic diseases; however, ERCP requires a high level of technical skill and experience, and there is always a risk of complications. ERCP-related duodenal perforation is one of the most serious complications of ERCP, and although the incidence rate is relatively low, the mortality rate is high. Recently, the introduction of new classification methods and the development of endoscopic technology and equipment have made endoscopic therapy a new trend. This may change the management strategy of perforation. Therefore, we reviewed the latest developments in endoscopic management, surgical management, and conservative internal medicine management. In addition to introducing many new endoscope treatment methods, we also discussed the timing of interventions, the progress of endoscope and surgical indications, and corresponding prevention strategies. We aim to retrospectively analyse these treatment modalities to propose appropriate solutions to improve dynamic clinical therapy.
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Herein, a new multidentate ligand, 5-(imidazol-1-yl)-N'-(pyridin-4-ylmethylene) nicotinohydrazide (L), with an acylhydrazone group was synthesized and characterized. Subsequently, four porous Cd(ii)-MOFs, i.e. [Cd(L)(NO3)] n (1), [Cd(L)Cl] n (2), [Cd(L)Br] n (3), and [Cd(L)I] n (4), were assembled using the ligand L by a solvothermal method and characterized by single-crystal X-ray diffraction, infrared spectroscopy, thermogravimetric analysis, and powder X-ray diffraction. Structural analysis shows that the coordination environments around Cd(ii) in all the four compounds are different due to the different coordinated anions. Among them, the coordination geometries and the arrangement of five-coordinated groups of the compound 1 containing the coordinated NO3 - anions are significantly different from those of the other three compounds containing halides. However, all the four MOFs have similar one-dimensional rhombic channels. In these channels, both the nitrate ions and the halide ions are attached to the inner walls of the pores. The CO2 adsorption properties of 1-4 were studied at 273 K, and the results showed that these compounds exhibit different adsorption capacities for CO2 due to the presence of different ions in their pores.
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E-cadherin and SDC1 are markers of epithelial-to-mesenchymal transition (EMT) that can be used to assess tumour prognosis. SDC1 has different effects in various types of cancers. On the one hand, reduced expression of SDC1 can leads to advantage stages of some cancers, such as gastric and colorectal cancer. On the other hand, SDC1 overexpression can also promote the growth and proliferation of cancer cells in pancreatic and breast cancer. However, the function of SDC1 is influenced and regulated by many factors. Exfoliated extracellular domain HS chain can mediate the function of SDC1 and play an important role in the occurrence and development of cancer. SDC1 binds to various ligands and influences the growth and reproduction of cancer cells via the activation of Wnt, the long isoform of FLICE-inhibitory protein (FLIP long), vascular endothelial growth factor receptor (VEGFR), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and MAPK/c-Jun N-terminal kinase (JNK) and other pathways. Cadherins occur in several types, but this review focuses on classical cadherins. N-cadherin and P-cadherin are activated during tumour development, whereas E-cadherin is a tumour suppressor. The cellular signalling pathways involved in classical cadherins, such as Wnt and VEGFR pathways, are also related to SDC1. The activation of E-cadherin caused by SDC1 knockdown has also been observed. Despite this evidence, no articles regarding the relationship of SDC1 and cadherin activation have been published. This review summarises the expressions of these two molecules in different cancers and analyses their possible relationship to provide insights into future cancer research and clinical treatment.
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Caderinas/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Transdução de Sinais/fisiologia , Sindecana-1/metabolismo , Adesão Celular/fisiologia , Humanos , Sindecana-1/genéticaRESUMO
A new asymmetric ligand, 5-{3-[5-(4-methylphenyl)-1,3,4-oxadiazol-2-yl]phenyl}-2-(pyridin-3-yl)-1,3,4-oxadiazole (L5), which contains two oxadiazole rings, was synthesized and characterized. The assembly of symmetric 2,5-bis(pyridin-3-yl)-1,3,4-oxadiazole (L1) and asymmetric L5 with AgCO2CF3 in solution yielded two novel AgI complexes, namely catena-poly[[di-µ-trifluoroacetato-disilver(I)]-bis[µ-2,5-bis(pyridin-3-yl)-1,3,4-oxadiazole]], [Ag2(C2F3O2)2(C12H8N4O)2]n or [Ag2(µ2-O2CCF3)2(L1)2]n (1), and bis(µ3-5-{3-[5-(4-methylphenyl)-1,3,4-oxadiazol-2-yl]phenyl}-2-(pyridin-3-yl)-1,3,4-oxadiazole)tetra-µ3-trifluoroacetato-tetrasilver(I) dichloromethane monosolvate, [Ag4(C2F3O2)4(C22H15N5O2)2]·CH2Cl2 or [Ag2(µ3-O2CCF3)2(L5)]2·CH2Cl2 (2). Complex 1 displays a one-dimensional ring-chain motif, where dinuclear Ag2(CF3CO2)2 units alternate with Ag2(L1)2 macrocycles. This structure is different from previously reported Ag-L1 complexes with different anions. Complex 2 features a tetranuclear supramolecular macrocycle, in which each ligand adopts a tridentate coordination mode with the oxadiazole ring next to the p-tolyl ring coordinated and that next to the pyridyl ring free. Two L5 ligands are bound to two Ag1 centres through two oxadiazole N and two pyridyl N atoms to form a macrocycle. The other two oxadiazole N atoms coordinate to the two Ag2 centres of the Ag2(O2CCF3)4 dimer. Each CF3CO2- anion adopts a µ3-coordination mode, bridging the Ag1 and Ag2 centres to form a tetranuclear silver(I) complex. This study indicates that the donor ability of the bridging oxadiazole rings can be tuned by electron-withdrawing and -donating substituents. The emission properties of ligands L1 and L5 and complexes 1 and 2 were also investigated in the solid state.
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Three new one- (1D) and two-dimensional (2D) CuII coordination polymers, namely poly[[bis{µ2-4-amino-3-(pyridin-2-yl)-5-[(pyridin-3-ylmethyl)sulfanyl]-1,2,4-triazole}copper(II)] bis(methanesulfonate) tetrahydrate], {[Cu(C13H12N5S)2](CH3SO3)2·4H2O}n (1), catena-poly[[copper(II)-bis{µ2-4-amino-3-(pyridin-2-yl)-5-[(pyridin-4-ylmethyl)sulfanyl]-1,2,4-triazole}] dinitrate methanol disolvate], {[Cu(C13H12N5S)2](NO3)2·2CH3OH}n (2), and catena-poly[[copper(II)-bis{µ2-4-amino-3-(pyridin-2-yl)-5-[(pyridin-4-ylmethyl)sulfanyl]-1,2,4-triazole}] bis(perchlorate) monohydrate], {[Cu(C13H12N5S)2](ClO4)2·H2O}n (3), were obtained from 4-amino-3-(pyridin-2-yl)-5-[(pyridin-3-ylmethyl)sulfanyl]-1,2,4-triazole with pyridin-3-yl terminal groups and from 4-amino-3-(pyridin-2-yl)-5-[(pyridin-4-ylmethyl)sulfanyl]-1,2,4-triazole with pyridin-4-yl terminal groups. Compound 1 displays a 2D net-like structure. The 2D layers are further linked through hydrogen bonds between methanesulfonate anions and amino groups on the framework and guest H2O molecules in the lattice to form a three-dimensional (3D) structure. Compound 2 and 3 exhibit 1D chain structures, in which the complicated hydrogen-bonding interactions play an important role in the formation of the 3D network. These experimental results indicate that the coordination orientation of the heteroatoms on the ligands has a great influence on the polymeric structures. Moreover, the selection of different counter-anions, together with the inclusion of different guest solvent molecules, would also have a great effect on the hydrogen-bonding systems in the crystal structures.
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Four [Ag-Ag]2+ unit-encapsulated trimetallic cages 1-4 were synthesized from one new tripodal ligand L and silver salts in different solvent systems by a one-pot method. The formation of coordination cages occurred simultaneously with the condensation of amino groups and ketone. The remarkable structural feature of cages 1-4 is their spontaneous incorporation of [Ag-Ag]2+ cationic units. Moreover, the argentophilic interactions are modulated by the uncoordinated amino substituents. The study herein shows that modification and subtle changes of the cage structures could be realized by a one-pot synthetic method.
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OBJECTIVE: To investigate the significance of Th17/Treg imbalance in the development and treatment of primary immune thrombocytopenia (ITP) in children. METHODS: Thirty-two children diagnosed with ITP between May and August, 2015 and 22 healthy children were enrolled. Flow cytometry was used to determine the Th17/Treg ratio in peripheral blood of healthy children and children with ITP before and after treatment with immunoglobulin. RESULTS: Compared with the patients with ITP before treatment, the healthy children and the patients treated with immunoglobulin had a significantly lower percentage of Th17 cells in CD4+ T cells, a significantly lower Th17/Treg ratio, and a significantly higher percentage of Treg cells in CD4+ T cells in peripheral blood (P<0.05). In the 32 ITP children treated with immunoglobulin, 20 had complete response, 4 had response, and 8 had no response. The patients with complete response had a significantly lower percentage of Th17 cells in CD4+ T cells and a significantly lower Th17/Treg ratio in peripheral blood than the patients without response (P<0.05). CONCLUSIONS: The Th17/Treg imbalance can be found in children with ITP. Immunoglobulin can improve the cellular immune function by regulation of the Th17/Treg ratio. The Th17/Treg ratio may serve as an indicator for assessing the therapeutic effects of ITP.
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Púrpura Trombocitopênica Idiopática/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , MasculinoRESUMO
OBJECTIVE: To explore significance of serum soluble CD163(sCD163) and soluble CD25(sCD25) in diagnosis and guiding treatment of children with hemophagocytic lymphohistiocytosis (HLH). METHOD: Data of 42 cases of children with HLH, 32 cases of non-HLH children with infection presented to First Affiliated Hospital of Zhengzhou University pediatric clinic and ward were collected from December 2013 to December 2014. Twenty-four healthy children were enrolled into a normal control group in the same period.Peripheral venous blood specimens (3 ml) were taken from the children with HLH after fasting before treatment, two weeks after treatment and eight weeks after treatment.Peripheral venous blood specimens (3 ml) were also taken from children of non-HLH infected group and normal control group after fasting at the initial visit. Serum sCD163 and sCD25 levels in the peripheral blood in three groups were determined by ELISA. According to cause of disease, children with HLH were divided into infection-related HLH, tumor-related HLH, primary HLH and others; relationship between serum sCD163 and sCD25 level and cause of disease was analyzed. RESULT: Serum sCD163 of HLH group ((6 094 ± 2 769) µg/L) and serum sCD163 of non-HLH infection group ((2 174 ± 950) µg/L) were significantly higher than that of normal control group ((777 ± 256) µg/L), F=71.396, P<0.05), and the differences among groups were statistically significant (P<0.05); serum sCD25 of HLH group ((41 963 ± 31 821) ng/L) and serum sCD25 of non-HLH infection group ((6 700 ± 4 105) ng/L) were significantly higher than that of normal control group ((2 440 ± 1 870) ng/L, F=37.513, P<0.05).There was no statistically significant difference between the non-HLH infection group with the normal control group (P>0.05), and the difference between the remaining groups was statistically significant (P<0.05). And serum sCD163 and sCD25 level of HLH group had a positive linear correlation, and Pearson correlation coefficient r=0.742 (t=7.000, P<0.05). The difference of serum sCD163 and sCD25 level among the different cause of disease in HLH group was significant (P<0.05).Pairwise comparison showed that serum sCD163 and sCD25 level of tumor-associated HLH group significantly increased as compared with infection-associated HLH group (P<0.05), but the difference was not statistically significant between the other groups (all P>0.05). Serum sCD163 and sCD25 level of HLH group before treatment, 2 weeks and 8 weeks after treatment showed a statistically significant tendency of decrease (P<0.05). Seen from the ROC curve, when sCD163 cut-off point was 2 359.08 µg/L, the diagnostic sensitivity was 83.3%, and specificity was 83.9%.When sCD25 cut-off point was 14 901.024 ng/L, the diagnosis sensitivity was 76.2%, and specificity was 98.2%. CONCLUSION: Serum sCD163 and sCD25 levels may be used for diagnosis of HLH.Dynamically monitoring of serum sCD163 and sCD25 level can help to determine deterioration of HLH and guide treatment.
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Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Linfo-Histiocitose Hemofagocítica/sangue , Receptores de Superfície Celular/sangue , Estudos de Casos e Controles , Criança , Ensaio de Imunoadsorção Enzimática , Humanos , Subunidade alfa de Receptor de Interleucina-2/sangue , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/terapia , Curva ROC , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To explore the functions of connective tissue growth factor (CTGF) in the restoration of hair follicles with a mixture of human dermal papilla cells and human hair follicle outer root sheath cells in vitro in nude mice. METHODS: Human hair follicle outer root sheath cells (hfORS) and human hair dermal papilla cells (hDP) were cultured in vitro and mixed in a fixed ratio (hfORS: hDP = 5:1). Flow cytometry was used to detect the content of CD200(+) cells in human hair follicle outer root sheath cells.And 8 nude mice were divided randomly into 2 groups according to a random number table and back wounds produced. Group A was transplanted with cell mixture plus 20 µg/L CTGF. Group B was transplanted with cell mixture alone. After 8 weeks of transplantation, the development of hair follicle formation was observed histologically.PCR was used to detect the expression of human specific DNA and mice DNA in transplants. RESULTS: The portion of CD200(+) cells in cultured hfORS was 19.65%. At 8 weeks after implantation, hair follicle formation could be observed in Group A (268 ± 96) more than Group B (62 ± 20). The difference was statistically significant (P < 0.05). And PCR showed that there was human composition in transplant. CONCLUSION: CTGF can induce the formation of hair follicle by promoting the interference between hDP and hfORS.
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Fator de Crescimento do Tecido Conjuntivo/farmacologia , Folículo Piloso/citologia , Engenharia Tecidual/métodos , Animais , Transplante de Células , Células Cultivadas , Humanos , Masculino , Camundongos , Camundongos Nus , Células-Tronco/citologiaRESUMO
MicroRNAs regulate a host of physiological and pathological processes in mesenchymal stem cells (MSCs), although no published studies describe changes in microRNA expression or function in MSCs under in vitro hyperglycemic conditions. By using a microRNA microarray approach, we have identified that miRNA-32-5p expression is significantly reduced under hyperglycemic conditions in rat bone marrow-derived MSCs. Expression of miRNA-32-5p targets the 3'-untranslated region of the mRNA encoding phosphatase and tensin homologs deleted on chromosome 10 (PTEN), a negative regulator of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Exposure to high glucose levels reduced miR-32-5p expression, induced PTEN expression, and inhibited activation of the PI3K/Akt signaling pathway of MSCs. Conversely, overexpression of miR-32-5p inhibited the expression of PTEN, ameliorated the inhibitory effect of high glucose levels on the PI3K/Akt signaling pathway, and promoted cell cycle progression from G0/G1 to G2/M and S phases. Our study indicates that exposure of MSCs to hyperglycemic conditions reduces miR-32-5p expression and disturbs cell cycle progression through a PTEN-mediated inhibitory effect on the PI3K/Akt signaling pathway. In summary, MiR-32-5p is a potentially important therapeutic agent for preventing MSC dysfunction under hyperglycemic conditions.
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Ciclo Celular/efeitos dos fármacos , Glucose/farmacologia , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Regiões 3' não Traduzidas , Animais , Western Blotting , Medula Óssea/metabolismo , Células Cultivadas , Biologia Computacional/métodos , Regulação para Baixo , Ativação Enzimática , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/patologia , MicroRNAs/genética , Oligonucleotídeos/metabolismo , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Transdução de Sinais , Transfecção , Regulação para CimaRESUMO
OBJECTIVE: To explore the expression of endoplasmic reticulum stress (ERS) associated proteins in livers of severely burned rats and examine its potential significance. METHODS: Sixty-four Wistar rats were randomly divided into the control and burn groups (30% total body surface area full-thickness thermal injury) (n = 32 each). Livers were harvested at Day 1, 4, 7, 14 post-burn. Western blot was used to detect the expressions of endoplasmic reticulum stress associated proteins glucose regulated protein 78 (GRP78), C/EBP-homologous protein (CHOP), active caspase-12 and active caspase-3. Hepatic apoptosis was assessed by the assay of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). RESULTS: Compared with the control group, the expression of GRP78 became elevated at Day 1, 4, 7, 14 post-burn (1.29 ± 0.11 vs 1.00 ± 0.00, 1.28 ± 0.12 vs 0.95 ± 0.16, 1.29 ± 0.14 vs 0.93 ± 0.06, 1.41 ± 0.17 vs 1.02 ± 0.13 respectively); the expression of CHOP was higher at Day 1, 4 (1.72 ± 0.07 vs 1.00 ± 0.00, 1.82 ± 0.18 vs 1.46 ± 0.08 respectively) while active caspase-12 and active caspase-3 increased at Day 1, 4, 7 post-burn (2.05 ± 0.65 vs 1.00 ± 0.00, 2.16 ± 0.69 vs 0.95 ± 0.21, 1.98 ± 0.56 vs 0.90 ± 0.22; 1.96 ± 0.15 vs 1.00 ± 0.00, 1.40 ± 0.14 vs 1.07 ± 0.12, 1.77 ± 0.17 vs 1.15 ± 0.21 respectively); the apoptotic index(%) of hepatocytes was higher at Day 1, 4, 7, 14 post-burn (27.20 ± 3.63 vs 5.00 ± 0.71, 16.40 ± 1.52 vs 5.40 ± 1.14, 27.60 ± 1.82 vs 7.40 ± 1.14, 10.20 ± 1.92 vs 5.20 ± 1.64 respectively). All results were statistically significant (all P < 0.05). CONCLUSION: ERS activates and expressions of associated proteins GRP78, CHOP, active caspase-12 and active caspase-3 increase in livers of severely burned rats.