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1.
Nat Immunol ; 25(1): 54-65, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38062135

RESUMO

The nature of activation signals is essential in determining T cell subset differentiation; however, the features that determine T cell subset preference acquired during intrathymic development remain elusive. Here we show that naive CD4+ T cells generated in the mouse thymic microenvironment lacking Scd1, encoding the enzyme catalyzing oleic acid (OA) production, exhibit enhanced regulatory T (Treg) cell differentiation and attenuated development of experimental autoimmune encephalomyelitis. Scd1 deletion in K14+ thymic epithelia recapitulated the enhanced Treg cell differentiation phenotype of Scd1-deficient mice. The dearth of OA permitted DOT1L to increase H3K79me2 levels at the Atp2a2 locus of thymocytes at the DN2-DN3 transition stage. Such epigenetic modification persisted in naive CD4+ T cells and facilitated Atp2a2 expression. Upon T cell receptor activation, ATP2A2 enhanced the activity of the calcium-NFAT1-Foxp3 axis to promote naive CD4+ T cells to differentiate into Treg cells. Therefore, OA availability is critical for preprogramming thymocytes with Treg cell differentiation propensities in the periphery.


Assuntos
Ácido Oleico , Timócitos , Animais , Camundongos , Ácido Oleico/metabolismo , Timo , Linfócitos T Reguladores , Diferenciação Celular , Fatores de Transcrição Forkhead/genética
2.
Nature ; 591(7850): 438-444, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33627868

RESUMO

Stromal cells in adult bone marrow that express leptin receptor (LEPR) are a critical source of growth factors, including stem cell factor (SCF), for the maintenance of haematopoietic stem cells and early restricted progenitors1-6. LEPR+ cells are heterogeneous, including skeletal stem cells and osteogenic and adipogenic progenitors7-12, although few markers have been available to distinguish these subsets or to compare their functions. Here we show that expression of an osteogenic growth factor, osteolectin13,14, distinguishes peri-arteriolar LEPR+ cells poised to undergo osteogenesis from peri-sinusoidal LEPR+ cells poised to undergo adipogenesis (but retaining osteogenic potential). Peri-arteriolar LEPR+osteolectin+ cells are rapidly dividing, short-lived osteogenic progenitors that increase in number after fracture and are depleted during ageing. Deletion of Scf from adult osteolectin+ cells did not affect the maintenance of haematopoietic stem cells or most restricted progenitors but depleted common lymphoid progenitors, impairing lymphopoiesis, bacterial clearance, and survival after acute bacterial infection. Peri-arteriolar osteolectin+ cell maintenance required mechanical stimulation. Voluntary running increased, whereas hindlimb unloading decreased, the frequencies of peri-arteriolar osteolectin+ cells and common lymphoid progenitors. Deletion of the mechanosensitive ion channel PIEZO1 from osteolectin+ cells depleted osteolectin+ cells and common lymphoid progenitors. These results show that a peri-arteriolar niche for osteogenesis and lymphopoiesis in bone marrow is maintained by mechanical stimulation and depleted during ageing.


Assuntos
Arteríolas , Linfopoese , Osteogênese , Nicho de Células-Tronco , Tecido Adiposo/citologia , Envelhecimento , Animais , Células da Medula Óssea/citologia , Osso e Ossos/citologia , Feminino , Fatores de Crescimento de Células Hematopoéticas/metabolismo , Lectinas Tipo C/metabolismo , Linfócitos/citologia , Masculino , Camundongos , Receptores para Leptina/metabolismo , Fator de Células-Tronco , Células Estromais/citologia
3.
Proc Natl Acad Sci U S A ; 120(22): e2220159120, 2023 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-37216542

RESUMO

Osteolectin is a recently identified osteogenic growth factor that binds to Integrin α11 (encoded by Itga11), promoting Wnt pathway activation and osteogenic differentiation by bone marrow stromal cells. While Osteolectin and Itga11 are not required for the formation of the skeleton during fetal development, they are required for the maintenance of adult bone mass. Genome-wide association studies in humans reported a single-nucleotide variant (rs182722517) 16 kb downstream of Osteolectin associated with reduced height and plasma Osteolectin levels. In this study, we tested whether Osteolectin promotes bone elongation and found that Osteolectin-deficient mice have shorter bones than those of sex-matched littermate controls. Integrin α11 deficiency in limb mesenchymal progenitors or chondrocytes reduced growth plate chondrocyte proliferation and bone elongation. Recombinant Osteolectin injections increased femur length in juvenile mice. Human bone marrow stromal cells edited to contain the rs182722517 variant produced less Osteolectin and underwent less osteogenic differentiation than that of control cells. These studies identify Osteolectin/Integrin α11 as a regulator of bone elongation and body length in mice and humans.


Assuntos
Condrócitos , Osteogênese , Adulto , Camundongos , Animais , Humanos , Condrócitos/metabolismo , Osteogênese/fisiologia , Lâmina de Crescimento , Estudo de Associação Genômica Ampla , Osso e Ossos , Diferenciação Celular , Integrinas/metabolismo , Proliferação de Células
4.
Proc Natl Acad Sci U S A ; 120(43): e2304689120, 2023 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-37856544

RESUMO

The importance of classical CD8+ T cells in tumor eradication is well acknowledged. However, the anti-tumor activity of MHC (major histocompatibility complex) Ib-restricted CD8+ T (Ib-CD8+ T) cells remains obscure. Here, we show that CX3CR1-expressing Ib-CD8+ T cells (Ib-restricted CD8+ T cells) highly express cytotoxic factors, austerely resist exhaustion, and effectively eliminate various tumors. These Ib-CD8+ T cells can be primed by MHC Ia (MHC class Ia molecules) expressed on various cell types for optimal activation in a Tbet-dependent manner. Importantly, MHC Ia does not allogeneically activate Ib-CD8+ T cells, rather, sensitizes these cells for T cell receptor activation. Such effects were observed when MHC Ia+ cells were administered to tumor-bearing Kb-/-Db-/-mice. A similar population of tumoricidal CX3CR1+CD8+ T cells was identified in wild-type mice and melanoma patients. Adoptive transfer of Ib-CD8+ T cells to wild-type mice inhibited tumor progression without damaging normal tissues. Taken together, we demonstrate that MHC class Ia can prime Ib-CD8+ T cells for robust tumoricidal activities.


Assuntos
Linfócitos T CD8-Positivos , Antígenos de Histocompatibilidade Classe I , Humanos , Camundongos , Animais , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos H-2 , Antígenos de Histocompatibilidade/metabolismo , Camundongos Endogâmicos C57BL
5.
Dig Dis Sci ; 69(9): 3413-3425, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38987445

RESUMO

OBJECTIVE: The purpose of this work was to check the connection between parameters of lipid profile and body mass index (BMI) in relation to the occurrence of acute pancreatitis within a sample of adults from northern China. METHODOLOGY: A total of 123,214 participants from the Kailuan Group were incorporated into this prospective study. The subjects were categorized into quartiles on the basis of their initial levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). On the basis of BMI classification, the individuals in the study were divided into three distinct groups: normal weight, overweight, and obese. The data were analyzed to explore the correlation between lipid profile and BMI with acute pancreatitis. RESULTS: Over a period of 12.59 ± 0.98 years, during the median follow-up duration, a total of 410 new patients with acute pancreatitis were recorded. The occurrence rate and total occurrence of acute pancreatitis demonstrated an upward trend in correlation with elevated levels of TG, TC, and BMI. Following adjustment for multiple variables, it was observed that individuals in the fourth quartile of TG and TC levels demonstrated the highest likelihood of developing acute pancreatitis. Furthermore, our analysis revealed that a proportion of 19.29% of the correlation between BMI and the likelihood of experiencing acute pancreatitis can be attributed to the influence of elevated TG levels, whereas 12.69% of the association was mediated by higher TC. CONCLUSIONS: We found that hypertriglyceridemia, hypercholesterolemia, and obesity were risk factors for acute pancreatitis, especially in young and middle-aged men.TG and TC were the mediating factors between BMI and the risk of acute pancreatitis.


Assuntos
Índice de Massa Corporal , Hipercolesterolemia , Hipertrigliceridemia , Pancreatite , Humanos , Hipertrigliceridemia/epidemiologia , Hipertrigliceridemia/sangue , Hipertrigliceridemia/complicações , Masculino , Pancreatite/epidemiologia , Pancreatite/sangue , Pancreatite/etiologia , Pancreatite/diagnóstico , Feminino , Pessoa de Meia-Idade , Hipercolesterolemia/epidemiologia , Hipercolesterolemia/sangue , Adulto , Estudos Prospectivos , Fatores de Risco , China/epidemiologia , Doença Aguda , Triglicerídeos/sangue , Obesidade/epidemiologia , Obesidade/complicações , Obesidade/sangue , Idoso
6.
Proc Natl Acad Sci U S A ; 118(25)2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34140410

RESUMO

We previously described a new osteogenic growth factor, osteolectin/Clec11a, which is required for the maintenance of skeletal bone mass during adulthood. Osteolectin binds to Integrin α11 (Itga11), promoting Wnt pathway activation and osteogenic differentiation by leptin receptor+ (LepR+) stromal cells in the bone marrow. Parathyroid hormone (PTH) and sclerostin inhibitor (SOSTi) are bone anabolic agents that are administered to patients with osteoporosis. Here we tested whether osteolectin mediates the effects of PTH or SOSTi on bone formation. We discovered that PTH promoted Osteolectin expression by bone marrow stromal cells within hours of administration and that PTH treatment increased serum osteolectin levels in mice and humans. Osteolectin deficiency in mice attenuated Wnt pathway activation by PTH in bone marrow stromal cells and reduced the osteogenic response to PTH in vitro and in vivo. In contrast, SOSTi did not affect serum osteolectin levels and osteolectin was not required for SOSTi-induced bone formation. Combined administration of osteolectin and PTH, but not osteolectin and SOSTi, additively increased bone volume. PTH thus promotes osteolectin expression and osteolectin mediates part of the effect of PTH on bone formation.


Assuntos
Fatores de Crescimento de Células Hematopoéticas/metabolismo , Lectinas Tipo C/metabolismo , Osteogênese/efeitos dos fármacos , Hormônio Paratireóideo/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Osso Esponjoso/efeitos dos fármacos , Osso Esponjoso/patologia , Feminino , Fatores de Crescimento de Células Hematopoéticas/sangue , Fatores de Crescimento de Células Hematopoéticas/deficiência , Humanos , Lectinas Tipo C/sangue , Lectinas Tipo C/deficiência , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Osteoporose/sangue , Pré-Menopausa/sangue , Via de Sinalização Wnt/efeitos dos fármacos
7.
Lipids Health Dis ; 22(1): 190, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37946249

RESUMO

OBJECTIVE: To investigate the correlation between anthropometric indexes [cardiometabolic index (CMI), lipid accumulation products (LAP), waist triglyceride index (WTI), and body mass index (BMI)] and acute pancreatitis (AP) in a Chinese adult population. METHODOLOGY: The present investigation consisted of a prospective group including 117,326 subjects who were enrolled in the Kailuan investigation. The individuals were categorized into quartiles based on their baseline levels of CMI, LAP, and WIT. BMI was categorized into three distinctive groups: normal weight group (BMI < 24 kg/m2), overweight group (BMI 24-28 kg /m2), and obesity group (BMI ≥ 28 kg/m2). The data were subjected to analysis in order to investigate the correlation between these anthropometric indexes and the incidence of AP. Cox regression models were employed to assess the relative risk of AP while accounting for known risk factors through appropriate adjustments. OUTCOMES: Over the course of a median follow-up duration of 12.59 ± 0.98 years, we documented 401 incident AP cases. Incidence density and cumulative incidence rates of AP increased with the increase of CMI, LAP, and WTI. After multivariate adjustment, the fourth quartile of CMI, LAP, and WTI exhibited the greatest risk of AP [CMI: hazard ratio (HR) 1.93, 95% confidential interval (CI) (1.45-2.57); LAP: HR 2.00, 95% CI(1.49-2.68); WTI: HR 2.13,95% CI (1.59-2.83)]. In comparison to the normal weight group, the obesity group (BMI ≥ 28 kg/m2) had an elevated risk of AP (HR = 1.58, 95% CI: 1.21-2.05). Furthermore, the incremental effect of BMI combined with CMI on the prognostic value of AP was greater than that of BMI alone (the C statistics demonstrated a result of 0.607 versus 0.546; the integrated discrimination improvement revealed a result of 0.321%; net reclassification improvement was 1.975%). CONCLUSION: We found that CMI, LAP, and WTI were positively and independently connected to the risk of AP. Additionally, CMI demonstrates a superior prognostic capacity than other indexes in anticipating AP.


Assuntos
Doenças Cardiovasculares , Produto da Acumulação Lipídica , Pancreatite , Humanos , Adulto , Triglicerídeos , Estudos Prospectivos , Doença Aguda , Pancreatite/epidemiologia , Obesidade/epidemiologia , Fatores de Risco , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , China/epidemiologia
8.
Proc Natl Acad Sci U S A ; 117(5): 2462-2472, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-31953260

RESUMO

Preadipocytes can give rise to either white adipocytes or beige adipocytes. Owing to their distinct abilities in nutrient storage and energy expenditure, strategies that specifically promote "beiging" of adipocytes hold great promise for counterbalancing obesity and metabolic diseases. Yet, factors dictating the differentiation fate of adipocyte progenitors remain to be elucidated. We found that stearoyl-coenzyme A desaturase 1 (Scd1)-deficient mice, which resist metabolic stress, possess augmentation in beige adipocytes under basal conditions. Deletion of Scd1 in mature adipocytes expressing Fabp4 or Ucp1 did not affect thermogenesis in mice. Rather, Scd1 deficiency shifted the differentiation fate of preadipocytes from white adipogenesis to beige adipogenesis. Such effects are dependent on succinate accumulation in adipocyte progenitors, which fuels mitochondrial complex II activity. Suppression of mitochondrial complex II by Atpenin A5 or oxaloacetic acid reverted the differentiation potential of Scd1-deficient preadipocytes to white adipocytes. Furthermore, supplementation of succinate was found to increase beige adipocyte differentiation both in vitro and in vivo. Our data reveal an unappreciated role of Scd1 in determining the cell fate of adipocyte progenitors through succinate-dependent regulation of mitochondrial complex II.


Assuntos
Complexo II de Transporte de Elétrons/metabolismo , Gorduras/metabolismo , Obesidade/enzimologia , Estearoil-CoA Dessaturase/genética , Ácido Succínico/metabolismo , Adipócitos Bege/citologia , Adipócitos Bege/metabolismo , Adipogenia , Animais , Metabolismo Energético , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Obesidade/genética , Obesidade/metabolismo , Obesidade/fisiopatologia , Estearoil-CoA Dessaturase/metabolismo , Termogênese
9.
Sensors (Basel) ; 21(13)2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34199103

RESUMO

Efficient, high-precision, and automatic measurement of tunnel structural changes is the key to ensuring the safe operation of subways. Conventional manual, static, and discrete measurements cannot meet the requirements of rapid and full-section detection in subway construction and operation. Mobile laser scanning technology is the primary method for tunnel detection. Herein, we propose a method to calculate shield tunnel displacements of a full cross-section tunnel. The point cloud data, obtained via a mobile tunnel deformation detection system, were fitted, projected, and interpolated to generate an orthophoto image. Combined with the cumulative characteristics of the tunnel gray gradient, the longitudinal ring seam of the tunnel was identified, while the Canny algorithm and Hough line detection algorithm identified the transverse seam. The symmetrical vertical foot method and cross-section superposition analysis were used to calculate the circumferential and radial displacements, respectively. The proposed displacement calculation method achieves automatic recognition of a ring seam, reduces human-computer interaction, and is fast, intelligent, and accurate. Furthermore, the description of the tunnel deformation location and deformation amount is more quantitative and specific. These results confirm the significance of shield tunnel displacement monitoring based on mobile monitoring systems in tunnel disease monitoring.


Assuntos
Algoritmos , Computadores , Eletrocardiografia , Humanos
10.
Sensors (Basel) ; 20(4)2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32069916

RESUMO

With the ongoing developments in laser scanning technology, applications for describing tunnel deformation using rich point cloud data have become a significant topic of investigation. This study describes the independently developed CNU-TS-2 mobile tunnel monitoring system for data acquisition, which has an electric system to control its forward speed and is compatible with various laser scanners such as the Faro and Leica models. A comparison with corresponding data acquired by total station data demonstrates that the data collected by CNU-TS-2 is accurate. Following data acquisition, the overall and local deformation of the tunnel is determined by denoising and 360° deformation analysis of the point cloud data. To enhance the expression of the analysis results, this study proposes an expansion of the tunnel point cloud data into a two-dimensional image via cylindrical projection, followed by an expression of the tunnel deformation through color difference to visualize the deformation. Compared with the three-dimensional modeling method of visualization, this method is easier to implement and facilitates storage. In addition, it is conducive to the performance of comprehensive analysis of problems such as water leakage in the tunnel, thereby achieving the effect of multiple uses for a single image.

11.
Sensors (Basel) ; 19(9)2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-31035415

RESUMO

It is valuable to study the land use/land cover (LULC) classification for suburbs. The fusion of Light Detection and Ranging (LiDAR) data and aerial imagery is often regarded as an effective method for the LULC classification; however, more in-depth analysis would be required to explore effective information for enhancing the suburban LULC classification. In this study, first, both aerial imageries and point clouds were simultaneously collected. Then, LiDAR-derived models, i.e., normalized digital surface model (nDSM) and surface intensity model (IM), were generated from the elevation and intensity of point clouds. Further, considering the surface characteristics of ground objects in suburb, we proposed a new LiDAR-derived model, namely surface roughness model (RM), to reveal the degree of surface fluctuations. Additionally, various combinations of aerial imageries and the LiDAR-derived data were used to analyze the effects of multi-variable fusion under different scenarios and optimize the multi-variable integration for suburban LULC classification. The mean decrease impurity method was used to identify the importance of variables; three machine learning classifiers, i.e., random forest (RF), k-nearest neighbor (KNN) and artificial neural network (ANN) were adopted in various scenarios. The results were as follows. The fusion of aerial imagery and all the LiDAR-derived models, i.e., nDSM, RM and IM, with RF classifier performs best in the suburban LULC classification (overall accuracy = 84.75%, kappa coefficient = 0.80). Variable importance analysis shows that nDSM has the highest variable importance proportion (VIP) value, followed by RM, IM, and spectral information, indicating the feasibility of this proposed LiDAR-derived model-RM. This research presents effective methods relating to the application of aerial imagery and LiDAR-derived model for the complex suburban surface scenarios.

12.
Cell Immunol ; 326: 24-32, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28778535

RESUMO

Stem cells are characterized by self-renew and multipotent differentiation abilities. Besides their roles in cell compensation, stem cells are also rich sources of growth factors, cytokines, chemokines, micro-RNAs and exosomes and serve as drug stores to maintain tissue homeostasis. Recent studies have revealed that the secretome of stem cells is regulated by the local inflammatory cues and highlighted the roles of these secretory factors in stem cell based therapies. Importantly, stem cell conditioned medium, in the absence of stem cell engraftment, have shown efficiency in treating diseases involves immune disorders. In this review, we summarize the recent advances in understanding the regulatory effects of stem cells secreted factors on different immune cells including macrophages, dendritic cells, neutrophils, NK cells, T cells, and B cells. We also discuss how stem cells released factors participate in the initiation, maintenance and resolution of inflammation. The in depth understanding of interaction between stem cells secreted factors and immune system would lead to new strategies to restore tissue homeostasis and improve the efficiency of stem cell therapies.


Assuntos
Diferenciação Celular/imunologia , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Leucócitos/citologia , Células-Tronco/metabolismo , Animais , Humanos , Leucócitos/imunologia
13.
Sensors (Basel) ; 18(2)2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29389856

RESUMO

A rapid, precise and automated means for the regular inspection and maintenance of a large number of tunnels is needed. Based on the depth study of the tunnel monitoring method, the CNU-TS-1 mobile tunnel monitoring system (TS1) is developed and presented. It can efficiently obtain the cross-sections that are orthogonal to the tunnel in a dynamic way, and the control measurements that depend on design data are eliminated. By using odometers to locate the cross-sections and correcting the data based on longitudinal joints of tunnel segment lining, the cost of the system has been significantly reduced, and the interval between adjacent cross-sections can reach 1-2 cm when pushed to collect data at a normal walking speed. Meanwhile, the relative deformation of tunnel can be analyzed by selecting cross-sections from original data. Through the measurement of the actual tunnel, the applicability of the system for tunnel deformation detection is verified, and the system is shown to be 15 times more efficient than that of the total station. The simulation experiment of the tunnel deformation indicates that the measurement accuracy of TS1 for cross-sections is 1.1 mm. Compared with the traditional method, TS1 improves the efficiency as well as increases the density of the obtained points.

14.
Mol Genet Genomics ; 291(1): 93-105, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26174736

RESUMO

Parthenocarpic fruit is a very attractive trait for consumers and especially in eggplants where seeds can lead to browning of the flesh and bitterness. However, the molecular mechanisms underlying parthenocarpy in eggplant still remain unknown. Some auxin response factors have been previously shown in model species, such as Arabidopsis and tomato, to play an important role in such a process. Here, we have identified a natural parthenocarpic mutant and showed that ARF8 from eggplant (SmARF8), is down-regulated in buds compared to wild-type plants. Further characterization of SmARF8 showed that it is a nuclear protein and an active transcriptional regulator. We determined that amino acids 629-773 of SmARF8 act as the transcriptional activation domain, the C terminus of SmARF8 is the protein-binding domain, and that SmARF8 might form homodimers. Expression analysis in eggplant showed that SmARF8 is expressed ubiquitously in all tissues and organs and is responsive to auxin. Eggplant transgenic lines harboring RNA interference of SmARF8 exhibited parthenocarpy in unfertilized flowers, suggesting that SmARF8 negatively regulates fruit initiation. Interestingly, SmARF8-overexpressing Arabidopsis lines also induced parthenocarpy. These results indicate that SmARF8 could affect the dimerization of auxin/indole acetic acid repressors with SmARF8 via domains III and IV and thus induce fruit development. Furthermore, the introduction of SmARF8 full-length cDNA could partially complement the parthenocarpic phenotypes in Arabidopsis arf8-1 and arf8-4 mutants. Collectively, our results demonstrate that SmARF8 may act as a key negative regulator involved in parthenocarpic fruit development of eggplant. These findings give more insights into the conserved mechanisms leading to parthenocarpy in which auxin signaling plays a pivotal role, and provide potential target for eggplant breeding.


Assuntos
Proteínas de Plantas/genética , Solanum melongena/genética , Fatores de Transcrição/genética , Proteínas de Ligação a DNA/genética , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Flores/efeitos dos fármacos , Flores/genética , Frutas/efeitos dos fármacos , Frutas/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/genética , Ácidos Indolacéticos/farmacologia , Mutação/efeitos dos fármacos , Mutação/genética , Plantas Geneticamente Modificadas/efeitos dos fármacos , Plantas Geneticamente Modificadas/genética , Sementes/efeitos dos fármacos , Sementes/genética , Solanum melongena/efeitos dos fármacos
15.
J Immunol ; 192(1): 103-9, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24293629

RESUMO

Mesenchymal stem cells (MSCs) possess potent immunosuppression capacity and could exert strong therapeutic effects in many diseases, especially inflammatory disorders, in animal models and clinical settings. Although inflammatory cytokines are critical in inducing the immune modulatory properties of MSCs, detailed molecular mechanisms are yet to be fully understood. TGF-ß is a well-known anti-inflammatory cytokine and exists in various inflammatory processes; therefore, we investigated whether it could synergize with MSCs in suppressing immune responses. To our surprise, we found that TGF-ß actually reversed the immunosuppressive effect of MSCs on anti-CD3 activated splenocytes. Using TGF-ß unresponsive MSCs, we demonstrated that the TGF-ß directly acted on MSCs. Furthermore, we showed that the effect of TGF-ß is exerted through inhibiting inflammatory cytokines induced inducible NO synthase (iNOS) expression in a SMAD3-dependent manner. Interestingly, we found that TGF-ß produced by MSCs could act in an autocrine manner to reduce inflammatory cytokine-induced inducible NO synthase expression by MSCs themselves. Therefore, our study revealed a previously unrecognized property of TGF-ß in promoting immune responses in the presence of MSCs.


Assuntos
Tolerância Imunológica/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/imunologia , Fator de Crescimento Transformador beta/farmacologia , Animais , Comunicação Autócrina/imunologia , Regulação da Expressão Gênica/efeitos dos fármacos , Tolerância Imunológica/genética , Células-Tronco Mesenquimais/metabolismo , Camundongos , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Proteína Smad3/metabolismo , Transcrição Gênica
16.
J Sep Sci ; 39(3): 545-51, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26576704

RESUMO

In this work, bentonite magnetic nanoparticles synthesized by a typical coprecipitation method were used as the adsorbent for the magnetic solid-phase extraction of six quinolones (ciprofloxacin, difloxacin, enrofloxacin, norfloxacin, sarafloxacin, and lomefloxacin) from milk samples followed by high-performance liquid chromatography with fluorimetric detection. Under the optimized conditions, the linear quantitation range for the six quinolones was 0.3-200 ng/mL, and the correlation coefficients of the calibration curves ranged from 0.9994 to 0.9999. The detection limit of the method was 0.1 ng/mL. Recoveries of quinolones from pure and low-fat spiked milk samples varied from 80.4 to 92.7% and from 81.3 to 93.5%, respectively. These results demonstrated that the proposed method for the determination of six quinolones in milk samples was rapid, reliable, and efficient.


Assuntos
Bentonita/química , Cromatografia Líquida de Alta Pressão/métodos , Fluorometria/métodos , Nanopartículas de Magnetita , Adsorção , Concentração de Íons de Hidrogênio , Limite de Detecção , Microscopia Eletrônica de Varredura , Reprodutibilidade dos Testes , Microextração em Fase Sólida
17.
J Sep Sci ; 39(22): 4398-4407, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27641624

RESUMO

In this study, the magnetic materials known as polymerized ionic liquid@3-(trimethoxysilyl)propyl methacrylate@Fe3 O4 nanoparticles were synthesized and utilized as potential adsorbents. First, these nanoparticles were applied to the analysis of sulfonamides and quinolones present in different water samples using magnetic solid phase extraction and high-performance liquid chromatography. Under optimized conditions, the developed method showed excellent detection sensitivity, with limits of detection (S/N = 3) and quantification limits (S/N = 10) within 0.2-1.0 and 0.8-3.4 µg/L, respectively. The spiked recoveries of the SAs and QNs in environmental water samples ranged from 83.5 to 103.0%, with RSDs of less than 4.5%. In addition, the adsorbents effectively removed sulfamethoxazole and ofloxacin present in existing aquatic environments. The adsorption kinetics and isotherms of sulfamethoxazole and ofloxacin on the magnetic adsorbents were studied to assess removal performance. The results indicate that the adsorption process follows a pseudo-second-order mechanism, which reveals that the sorption mechanism is the rate-limiting step and produces high qmax values (sulfamethoxazole = 70.35 mg/g and ofloxacin = 48.95 mg/g), thus demonstrating the enormous adsorption capacity of these magnetic adsorbents.


Assuntos
Quinolonas/isolamento & purificação , Sulfonamidas/isolamento & purificação , Poluentes Químicos da Água/isolamento & purificação , Adsorção , Cromatografia Líquida de Alta Pressão , Magnetismo , Metacrilatos , Nanopartículas , Compostos de Organossilício , Extração em Fase Sólida
18.
J Biol Chem ; 288(16): 11074-9, 2013 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-23449975

RESUMO

MSCs possess potent immunosuppressive capacity. We have reported that mouse MSCs inhibit T cell proliferation and function via nitric oxide. This immune regulatory capacity of MSCs is induced by the inflammatory cytokines IFNγ together with either TNFα or IL-1ß. This effect of inflammatory cytokines on MSCs is extraordinary; logarithmic increases in the expression of iNOS and chemokines are often observed. To investigate the molecular mechanisms underlying this robust effect of cytokines, we examined the expression of microRNAs in MSCs before and after cytokine treatment. We found that miR-155 is most significantly up-regulated. Furthermore, our results showed that miR-155 inhibits the immunosuppressive capacity of MSCs by reducing iNOS expression. We further demonstrated that miR-155 targets TAK1-binding protein 2 (TAB2) to regulate iNOS expression. Additionally, knockdown of TAB2 reduced iNOS expression. In summary, our study demonstrated that miR-155 inhibits the immunosuppressive capacity of MSCs by reducing iNOS expression by targeting TAB2. Our data revealed a novel role of miR-155 in regulating the immune modulatory activities of MSCs.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/imunologia , Regulação Enzimológica da Expressão Gênica/imunologia , Tolerância Imunológica/fisiologia , Células-Tronco Mesenquimais/imunologia , MicroRNAs/imunologia , Óxido Nítrico Sintase Tipo II/imunologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Linhagem Celular , Regulação Enzimológica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Humanos , Interferon gama/genética , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-1beta/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Óxido Nítrico Sintase Tipo II/biossíntese , Óxido Nítrico Sintase Tipo II/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo
19.
J Fluoresc ; 24(1): 143-52, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23900848

RESUMO

The complex characteristics of p-sulfonated calix[n]arene (SCnA) and two tryptophans N-[(tert-butoxy) carbonyl]-tryptophan (trp-A) and N-carbobenzoxy-tryptophane (trp-B) were examined through various techniques. Spectrofluorimetry was performed at different temperatures to determine the stability constants and evaluate the thermodynamic parameters of the two complexes. The effect of pH on complex formation was estimated. According to the fluorescence data, the assumption about the steric hindrance of the tert-butyl group of trp-A and the phenyl group of trp-B was put forward. (1)H NMR was also performed to determine the binding interaction mechanism. Results showed that the indole benzene rings of the two tryptophans partly penetrated into the cavity of p-sulfonated calix[n]arene. The shift in Ha, Hb and Hc, Hd positions became more significant as the number of phenolic units of the calixarene ring increased. Molecular modeling of the complexes elucidated the assumption about the steric hindrance of the tert-butyl group of trp-A and the phenyl group of trp-B. These observations of molecular modeling computation are consistent with previous fluorescence data and (1)H NMR results.


Assuntos
Calixarenos/química , Ácidos Sulfônicos/química , Triptofano/química , Substâncias Macromoleculares/química , Modelos Moleculares , Estrutura Molecular , Espectrometria de Fluorescência
20.
Plant Phenomics ; 6: 0145, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38332900

RESUMO

Identifying the spatiotemporal distributions and phenotypic characteristics of understory saplings is beneficial in exploring the internal mechanisms of plant regeneration and providing technical assistances for continues cover forest management. However, it is challenging to detect the understory saplings using 2-dimensional (2D) spectral information produced by conventional optical remotely sensed data. This study proposed an automatic method to detect the regenerated understory saplings based on the 3D structural information from aerial laser scanning (ALS) data. By delineating individual tree crown using the improved spectral clustering algorithm, we successfully removed the overstory canopy and associated trunk points. Then, individual understory saplings were segmented using an adaptive-mean-shift-based clustering algorithm. This method was tested in an experimental forest farm of North China. Our results showed that the detection rates of understory saplings ranged from 94.41% to 152.78%, and the matching rates increased from 62.59% to 95.65% as canopy closure went down. The ALS-based sapling heights well captured the variations of field measurements [R2 = 0.71, N = 3,241, root mean square error (RMSE) = 0.26 m, P < 0.01] and terrestrial laser scanning (TLS)-based measurements (R2 = 0.78, N =443, RMSE = 0.23 m, P < 0.01). The ALS-based sapling crown width was comparable with TLS-based measurements (R2 = 0.64, N = 443, RMSE = 0.24 m). This study provides a solution for the quantification of understory saplings, which can be used to improve forest ecosystem resilence through regulating the dynamics of forest gaps to better utilize light resources.

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