Objective Thyroid-associated ophthalmopathy(TAO)is an autoimmune disorder involving the orbital tissue.This study aimed to understand the role of regulatory T cells(Tregs)in TAO during 12-week systemic glucocorticoid(...Objective Thyroid-associated ophthalmopathy(TAO)is an autoimmune disorder involving the orbital tissue.This study aimed to understand the role of regulatory T cells(Tregs)in TAO during 12-week systemic glucocorticoid(GC)treatment.Methods Thirty-two moderate-severe TAO patients with a clinical activity score(CAS)≥3/7 or with prolonged T2 relaxation time(T2RT)on at least one side of extraocular muscle(EOM)were enrolled.The percentage of the peripheral CD4+CD25(high)CD127(−/low)Tregs was analyzed using flow cytometry before and after the GC treatment.The activity and severity of TAO,T2RT,and the clinical outcomes after the GC treatment were assessed.Their correlation with the peripheral Tregs was investigated.Results There was no significant association between the baseline Treg fraction and the activity and severity of TAO or the treatment response.A significant reduction of Tregs was observed after the GC therapy merely in patients without any clinical improvement.Conclusion Treg reduction after systemic GC therapy is indicative of a poor therapeutic response.Accordingly,dynamic alterations of Tregs could help to evaluate the effectiveness of the GC treatment.展开更多
Glycogen plays essential roles in glucose metabolism.Imaging glycogen in the liver,the major glycogen reservoir in the body,may shed new light on many metabolic disorders.^(13)C magnetic resonance spectroscopy(MRS)has...Glycogen plays essential roles in glucose metabolism.Imaging glycogen in the liver,the major glycogen reservoir in the body,may shed new light on many metabolic disorders.^(13)C magnetic resonance spectroscopy(MRS)has become the mainstream method for monitoring glycogen in the body.However,the equipment of special hard-ware to standard clinical magnetic resonance imaging(MRI)scanners limits its clinical applications.Herein,we utilized endogenous glycogen as a T_(2)-based relaxation contrast agent for imaging glycogen metabolism in the liver in vivo.The in vitro results demonstrated that the transverse relaxation rate of glycogen strongly correlates with the concentration,pH,and field strength.Based on the Swift-Connick theory,we characterized the exchange property of glycogen and measured the exchange rate of glycogen as 31,847 Hz at 37°C.Besides,the viscosity and echo spacing showed no apparent effect on the transverse relaxation rate.This unique feature enables vi-sualization of glycogen signaling in vivo through T_(2)-weighted MRI.Two hours-post intraperitoneal injection of glucagon,a clinical drug to promote glycogenolysis and gluconeogenesis,the signal intensity of the mice’s liver increased by 1.8 times from the T_(2)-weighted imaging experiment due to the decomposition of glycogen.This study provides a convenient imaging strategy to non-invasively investigate glycogen metabolism in the liver,which may find clinical applications in metabolic diseases.展开更多
MR imaging of gene transcription is important as it should enable the non-invasive detection of mRNA alterations in disease. A range of MRI methods have been proposed for in vivo molecular imaging of cells based on th...MR imaging of gene transcription is important as it should enable the non-invasive detection of mRNA alterations in disease. A range of MRI methods have been proposed for in vivo molecular imaging of cells based on the use of ultra- small super-paramagnetic iron oxide (USPIO) nanoparticles and related susceptibility weighted imaging methods. Al-though immunohistochemistry can robustly differentiate the expression of protein variants, there is currently no direct gene assay technique that is capable of differentiating established to differentiate the induction profiles of c-Fos mRNA in vivo. To visualize the differential FosB gene expression profile in vivo after burn trauma, we developed MR probes that link the T2* contrast agent [superparamagnetic iron oxide nanoparticles (SPION)] with an oligodeoxynucleotide (ODN) sequence complementary to FosB mRNA to visualize endogenous mRNA targets via in vivo hybridization. The presence of this SPION-ODN probe in cells results in localized signal reduction in T2*-weighted MR images, in which the rate of signal reduction (R2*) reflects the regional iron concentration at different stages of amphetamine (AMPH) exposure in living mouse tissue. Our aim was to produce a superior contrast agent that can be administered using sys- temic as opposed to local administration and which will target and accumulate at sites of burn injury. Specifically, we developed and evaluated a PEGylated lipid coated MR probe with ultra-small super-paramagnetic iron oxide nanoparti- cles (USPION, a T2 susceptibility agent) coated with cationic fusogenic lipids, used for cell transfection and gene de- livery and covalently linked to a phosphorothioate modified oligodeoxynucleotide (sODN) complementary to c-Fos mRNA (SPION-cFos) and used the agent to image mice with leg burns. Our study demonstrated the feasibility of monitoring burn injury using MR imaging of c-Fos transcription in vivo, in a clinically relevant mouse model of burn injury for the first time.展开更多
Background: The zone of calcified cartilage (ZCC) plays an important role in the pathogenesis of osteoarthritis (OA) but has never been imaged in vivo with magnetic resonance (MR) imaging techniques. We investigated t...Background: The zone of calcified cartilage (ZCC) plays an important role in the pathogenesis of osteoarthritis (OA) but has never been imaged in vivo with magnetic resonance (MR) imaging techniques. We investigated the feasibility of direct imaging of the ZCC in both cadaveric whole knee specimens and in vivo healthy knees using a 3-dimensional ultrashort echo time cones (3D UTE-Cones) sequence on a clinical 3T scanner. Methods: In all, 12 cadaveric knee joints and 10 in vivo healthy were collected. At a 3T MR scanner with an 8-channel knee coil, a fat-saturated 3D dual-echo UTE-Cones sequence was used to image the ZCC, following with a short rectangular pulse excitation and 3D spiral sampling with conical view ordering. The regions of interests (ROIs) were delineated by a blinded observer. Singlecomponent T2* and T2 values were calculated from fat-saturated 3D dual-echo UTE-Cones and a Carr-Purcell-Meiboom-Gill (T2 CPMG) data using a semi-automated MATLAB code. Results: The single-exponential fitting curve of ZCC was accurately obtained with R2 of 0.989. For keen joint samples, the ZCC has a short T2* ranging from 0.62 to 2.55 ms, with the mean ±standard deviation (SD) of 1.49 ±0.66 ms, and with 95% confidence intervals (CI) of 1.20-1.78 ms. For volunteers, the short T2* ranges from 0.93 to 3.52ms, with the mean±SD of 2.09±0.56 ms, and the 95% CI is 1.43 to 2.74ms in ZCC. Conclusions: The high-resolution 3D UTE-Cones sequence might be used to directly image ZCC in the human knee joint on a clinical 3T scanner with a scan time of more than 10 min. Using this non-invasive technique, the T2* relaxation time of the ZCC can be further detected.展开更多
基金supported by the National Natural Science Foundation of China(No.81100581)the Beijing Bethune Charitable Foundation(No.2021).
文摘Objective Thyroid-associated ophthalmopathy(TAO)is an autoimmune disorder involving the orbital tissue.This study aimed to understand the role of regulatory T cells(Tregs)in TAO during 12-week systemic glucocorticoid(GC)treatment.Methods Thirty-two moderate-severe TAO patients with a clinical activity score(CAS)≥3/7 or with prolonged T2 relaxation time(T2RT)on at least one side of extraocular muscle(EOM)were enrolled.The percentage of the peripheral CD4+CD25(high)CD127(−/low)Tregs was analyzed using flow cytometry before and after the GC treatment.The activity and severity of TAO,T2RT,and the clinical outcomes after the GC treatment were assessed.Their correlation with the peripheral Tregs was investigated.Results There was no significant association between the baseline Treg fraction and the activity and severity of TAO or the treatment response.A significant reduction of Tregs was observed after the GC therapy merely in patients without any clinical improvement.Conclusion Treg reduction after systemic GC therapy is indicative of a poor therapeutic response.Accordingly,dynamic alterations of Tregs could help to evaluate the effectiveness of the GC treatment.
基金This work is supported by the National Key R&D Program of China(2018YFA0704000)the National Natural Science Foundation of China(91859206,U21A20392,82127802 and 21921004)+2 种基金the Key Research Program of Frontier Sciences,Chinese Academy of Sciences(ZDBS-LY-JSC004)the Scientific Instrument Developing Project of the Chi-nese Academy of Sciences(GJJSTD20200002)Xin Zhou acknowledges the support from the Tencent Foundation through the XPLORER PRIZE.
文摘Glycogen plays essential roles in glucose metabolism.Imaging glycogen in the liver,the major glycogen reservoir in the body,may shed new light on many metabolic disorders.^(13)C magnetic resonance spectroscopy(MRS)has become the mainstream method for monitoring glycogen in the body.However,the equipment of special hard-ware to standard clinical magnetic resonance imaging(MRI)scanners limits its clinical applications.Herein,we utilized endogenous glycogen as a T_(2)-based relaxation contrast agent for imaging glycogen metabolism in the liver in vivo.The in vitro results demonstrated that the transverse relaxation rate of glycogen strongly correlates with the concentration,pH,and field strength.Based on the Swift-Connick theory,we characterized the exchange property of glycogen and measured the exchange rate of glycogen as 31,847 Hz at 37°C.Besides,the viscosity and echo spacing showed no apparent effect on the transverse relaxation rate.This unique feature enables vi-sualization of glycogen signaling in vivo through T_(2)-weighted MRI.Two hours-post intraperitoneal injection of glucagon,a clinical drug to promote glycogenolysis and gluconeogenesis,the signal intensity of the mice’s liver increased by 1.8 times from the T_(2)-weighted imaging experiment due to the decomposition of glycogen.This study provides a convenient imaging strategy to non-invasively investigate glycogen metabolism in the liver,which may find clinical applications in metabolic diseases.
文摘MR imaging of gene transcription is important as it should enable the non-invasive detection of mRNA alterations in disease. A range of MRI methods have been proposed for in vivo molecular imaging of cells based on the use of ultra- small super-paramagnetic iron oxide (USPIO) nanoparticles and related susceptibility weighted imaging methods. Al-though immunohistochemistry can robustly differentiate the expression of protein variants, there is currently no direct gene assay technique that is capable of differentiating established to differentiate the induction profiles of c-Fos mRNA in vivo. To visualize the differential FosB gene expression profile in vivo after burn trauma, we developed MR probes that link the T2* contrast agent [superparamagnetic iron oxide nanoparticles (SPION)] with an oligodeoxynucleotide (ODN) sequence complementary to FosB mRNA to visualize endogenous mRNA targets via in vivo hybridization. The presence of this SPION-ODN probe in cells results in localized signal reduction in T2*-weighted MR images, in which the rate of signal reduction (R2*) reflects the regional iron concentration at different stages of amphetamine (AMPH) exposure in living mouse tissue. Our aim was to produce a superior contrast agent that can be administered using sys- temic as opposed to local administration and which will target and accumulate at sites of burn injury. Specifically, we developed and evaluated a PEGylated lipid coated MR probe with ultra-small super-paramagnetic iron oxide nanoparti- cles (USPION, a T2 susceptibility agent) coated with cationic fusogenic lipids, used for cell transfection and gene de- livery and covalently linked to a phosphorothioate modified oligodeoxynucleotide (sODN) complementary to c-Fos mRNA (SPION-cFos) and used the agent to image mice with leg burns. Our study demonstrated the feasibility of monitoring burn injury using MR imaging of c-Fos transcription in vivo, in a clinically relevant mouse model of burn injury for the first time.
文摘Background: The zone of calcified cartilage (ZCC) plays an important role in the pathogenesis of osteoarthritis (OA) but has never been imaged in vivo with magnetic resonance (MR) imaging techniques. We investigated the feasibility of direct imaging of the ZCC in both cadaveric whole knee specimens and in vivo healthy knees using a 3-dimensional ultrashort echo time cones (3D UTE-Cones) sequence on a clinical 3T scanner. Methods: In all, 12 cadaveric knee joints and 10 in vivo healthy were collected. At a 3T MR scanner with an 8-channel knee coil, a fat-saturated 3D dual-echo UTE-Cones sequence was used to image the ZCC, following with a short rectangular pulse excitation and 3D spiral sampling with conical view ordering. The regions of interests (ROIs) were delineated by a blinded observer. Singlecomponent T2* and T2 values were calculated from fat-saturated 3D dual-echo UTE-Cones and a Carr-Purcell-Meiboom-Gill (T2 CPMG) data using a semi-automated MATLAB code. Results: The single-exponential fitting curve of ZCC was accurately obtained with R2 of 0.989. For keen joint samples, the ZCC has a short T2* ranging from 0.62 to 2.55 ms, with the mean ±standard deviation (SD) of 1.49 ±0.66 ms, and with 95% confidence intervals (CI) of 1.20-1.78 ms. For volunteers, the short T2* ranges from 0.93 to 3.52ms, with the mean±SD of 2.09±0.56 ms, and the 95% CI is 1.43 to 2.74ms in ZCC. Conclusions: The high-resolution 3D UTE-Cones sequence might be used to directly image ZCC in the human knee joint on a clinical 3T scanner with a scan time of more than 10 min. Using this non-invasive technique, the T2* relaxation time of the ZCC can be further detected.
