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1.
Echocardiography ; 41(5): e15835, 2024 May.
Article in English | MEDLINE | ID: mdl-38784978

ABSTRACT

PURPOSE: There is currently limited information on the utility of transthoracic echocardiography (TTE)-derived Doppler parameters for assessing bioprosthetic tricuspid valve (BTV) dysfunction. Our study aimed to establish the precision and appropriate reference ranges for routinely collected transthoracic Doppler parameters in the assessment of BTV dysfunction. METHODS: We retrospectively evaluated 100 BTV patients who underwent TTE. Based on redo surgical confirmation or more than 2 repeat TTE or transesophageal echocardiography (TEE) examinations, patients were allocated to normal (n = 61), regurgitant (n = 24), or stenotic (n = 15) BTV group. Univariate and multivariate binary logistic regression were performed to identify TTE Doppler parameters that detected BTV dysfunction. RESULTS: The VTI ratio (VTITV/VTILVOT) was the most accurate Doppler parameter for detecting BTV dysfunction, with a ratio of >2.8 showing 84.6% sensitivity and 90.2% specificity. VTI ratio > 3.2, mean gradient (MGTV) > 6.2 mmHg and pressure half-time > 218 ms detected significant BTV stenosis, with sensitivities of 100%, 93.3% and 93.3% and specificities of 82.4%, 75.3% and 87.1%, respectively. After multivariate analysis, the VTI ratio > 2.8 (OR = 9.00, 95% CI = 2.13-41.61, p = .003) and MGTV > 5.1 mmHg (OR = 6.50, 95% CI = 1.69-27.78, p = .008) were the independent associations of BTV dysfunction. With these cutoff values, 75.0%-92.2% of normal and 62.5%-96.0% of dysfunctional BTV were identified. CONCLUSIONS: Doppler parameters from TTE can accurately identify BTV dysfunction, particularly with VTI ratio > 2.8 and MGTV > 5.1 mmHg, to assess the need for additional testing with TEE.


Subject(s)
Bioprosthesis , Echocardiography, Doppler , Heart Valve Prosthesis , Sensitivity and Specificity , Tricuspid Valve , Humans , Female , Male , Tricuspid Valve/diagnostic imaging , Tricuspid Valve/physiopathology , Middle Aged , Echocardiography, Doppler/methods , Retrospective Studies , Reproducibility of Results , Aged , Tricuspid Valve Insufficiency/physiopathology , Tricuspid Valve Insufficiency/diagnostic imaging
2.
J Nanobiotechnology ; 21(1): 37, 2023 Feb 02.
Article in English | MEDLINE | ID: mdl-36732759

ABSTRACT

BACKGROUND: Cancer stem cells (CSCs) are crucial for the growth, metastasis, drug resistance, recurrence, and spread of tumors. Napabucasin (NAP) could effectively inhibit CSC, but its mechanism has not been fully explained. Additionally, NAP also has the drawbacks of poor water solubility and low utilization. Therefore, this study not only elaborated the new mechanism of NAP inhibiting CSCs, but also built NAP-loaded nanoprobes using apoptotic tumor-derived microparticles (TMPs) as carriers to combine diagnose and treat of colon cancer and lessen the adverse effects of NAP. RESULTS: The study discovered a new mechanism for NAP inhibiting tumors. NAP, in addition to inhibiting STAT3, may also inhibit STAT1, thereby inhibiting the expression of CD44, and the stemness of colon cancer. N3-TMPs@NAP was successfully synthesized, and it possessed a lipid bilayer with a particle size of 220.13 ± 4.52 nm, as well as strong tumor binding ability and anti-tumor effect in vitro. In static PET/CT imaging studies, the tumor was clearly visible and showed higher uptake after N3-TMPs@NAP injection than after oral administration. The average tumor volume and weight of the N3-TMPs@NAP group on day 14 of the treatment studies were computed to be 270.55 ± 107.59 mm3 and 0.30 ± 0.12 g, respectively. These values were significantly lower than those of the other groups. Additionally, N3-TMPs@NAP might prevent colon cancer from spreading to the liver. Furthermore, due to TMPs' stimulation of innate immunity, N3-TMPs@NAP might stimulate anti-tumor. CONCLUSIONS: As a combined diagnostic and therapeutic nanoprobe, N3-TMPs@NAP could successfully conduct PET/CT imaging, suppress CSCs, and synergistically stimulate anticancer immune responses. Additionally, this nanoprobe might someday be employed in clinical situations because TMPs for it can be produced from human tissue and NAP has FDA approval.


Subject(s)
Cell-Derived Microparticles , Colonic Neoplasms , Humans , Cell Line, Tumor , Colonic Neoplasms/metabolism , Colonic Neoplasms/therapy , Neoplastic Stem Cells , Positron Emission Tomography Computed Tomography , Immunotherapy
3.
Cell Mol Biol Lett ; 28(1): 9, 2023 Jan 30.
Article in English | MEDLINE | ID: mdl-36717768

ABSTRACT

BACKGROUND: Bone marrow-derived mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs) have shown potent anti-inflammatory function in various pathological conditions, such as osteoarthritis and neurodegenerative diseases. Since the number of EVs naturally secreted by cells is finite and they usually bear specific repertoires of bioactive molecules to perform manifold cell-cell communication, but not one particular therapeutic function as expected, their practical application is still limited. Strategies are needed to increase the production of EVs and enhance their therapeutic function. Recent studies have suggested that low-intensity pulsed ultrasound (LIPUS) is a promising non-invasive method to increase the secretion of EVs and promote their anti-inflammatory effects. However, the effect of LIPUS stimulation of BMSCs on EVs derived from the cells remains unclear. The objective of this study was to investigate whether LIPUS stimulation on BMSCs could increase the secretion of EVs and enhance their anti-inflammatory effects. METHODS: BMSCs were exposed to LIPUS (300 mW/cm2) for 15 min and EVs were isolated by ultracentrifugation. Anti-inflammatory effects of EVs were investigated on RAW264.7 cells in vitro and in the allogeneic skin transplantation model. Small RNA-seq was utilized to identify components difference in EVs with/without LIPUS irradiation. RESULTS: In this study, we found that LIPUS stimulation could lead to a 3.66-fold increase in the EVs release from BMSCs. Moreover, both in vitro and in vivo experimental results suggested that EVs secreted from LIPUS-treated BMSCs (LIPUS-EVs) possessed stronger anti-inflammatory function than EVs secreted from BMSCs without LIPUS stimulation (C-EVs). RNA-seq analysis revealed that miR-328-5p and miR-487b-3p were significantly up-regulated in LIPUS-EVs compare with C-EVs. The suppression of MAPK signaling pathway by these two up-regulated miRNAs could be the potential mechanism of strengthened anti-inflammatory effects of LIPUS-EVs. CONCLUSION: LIPUS stimulation on BMSCs could significantly increase the secretion of EVs. Moreover, EVs generated from LIPUS-treated BMSCs possessed much stronger anti-inflammatory function than C-EVs. Therefore, LIPUS could be a promising non-invasive strategy to promote the production of EVs from BMSCs and augment their anti-inflammatory effects.


Subject(s)
Extracellular Vesicles , Mesenchymal Stem Cells , MicroRNAs , Mesenchymal Stem Cells/metabolism , Signal Transduction , MicroRNAs/metabolism , Extracellular Vesicles/metabolism , Ultrasonic Waves
4.
Int Heart J ; 64(6): 1040-1048, 2023.
Article in English | MEDLINE | ID: mdl-38030291

ABSTRACT

The prognosis of patients with nonvalvular atrial fibrillation (NVAF) with a low CHA2DS2-VASc score (0-1) following a stroke is not well studied. In this investigation, stroke risk factors and prognostic markers in low-risk NVAF patients who are nonetheless at risk for stroke were examined.From January 2012 to January 2022, we retrospectively assessed atrial fibrillation (AF) patients at Xiamen University's Zhongshan Hospital for ischemic stroke. Along with a control group of patients with CHA2DS2-VASc scores of 0-1 who weren't suffering from a stroke, patients with CHA2DS2-VASc scores of 0-1 at the time of stroke were included in the study. Using multivariate logistic regression, independent risk factors were identified. To assess the cumulative occurrences of in-hospital mortality in patients with NVAF-related stroke, the Kaplan-Meier method was used.The study included 156 out of 3.237 inpatients with AF-related stroke who had CHA2DS2-VASc ratings of 0-1. Left atrial diameter (LAD) (odds ratio [OR]: 1.858, 95% confidence interval (CI) 1.136-3.036, P = 0.013), D-dimer (OR: 2.569, 95% CI 1.274-5.179, P = 0.008), and NT-proBNP (OR: 4.558, 95% CI 2.060-10.087, P = 0.000) were found to be independent risk factors for stroke in NVAF patients with a low CHA2DS2-VASc score. During hospitalization, nine patients with NVAF-related stroke died. In patients with NVAF-related stroke, NT-proBNP (hazard ratio: 3.504, 95% CI 1.079-11.379, P = 0.037) was an indicator of mortality risk.Patients with NVAF and CHA2DS2-VASc scores of 0-1 had independent risk factors for stroke in the form of LAD, D-dimer, and NT-proBNP. Notably, in low-risk NVAF patients with stroke, NT-proBNP was discovered to be a potent predictor of in-hospital death.


Subject(s)
Atrial Fibrillation , Stroke , Humans , Prognosis , Retrospective Studies , Hospital Mortality , Risk Factors , Stroke/epidemiology , Stroke/etiology , Risk Assessment
5.
Rev Cardiovasc Med ; 23(11): 372, 2022 Nov.
Article in English | MEDLINE | ID: mdl-39076182

ABSTRACT

Background: The role of soluble interleukin-1 receptor type 2 (sIL-1R2) in acute myocardial infarction (AMI) remains undocumented. In the present study, we aimed to evaluate the possible associations of sIL-1R2 with left ventricular (LV) function, remodeling and future clinical events in the setting of AMI. Methods: Circulating sIL-1R2 levels were quantified after percutaneous coronary intervention (PCI) on day 1 of hospital admission for 204 AMI patients, and upon enrollment of 204 healthy controls. Echocardiography was conducted in the acute phase and at 12-month follow-up. Adverse clinical events were registered after 12 months. Results: Circulating sIL-1R2 levels were significantly higher in AMI patients than in healthy controls (medians respectively 6652.81 pg/mL, 3799.13 pg/mL, p < 0.0001). AMI patients with sIL-1R2 levels less than the median had a larger proportion of worsened LV ejection fraction [a decrease in LV ejection fraction (LVEF) of more than 10% units] and reduced LVEF (a final LVEF < 50%). After multivariate adjustment, sIL-1R2 levels less than the median were associated with an increased risk of worsened LVEF [odds ratio (OR): 3.7, 95% confidence interval (CI): 1.6-8.5, p = 0.002] and reduced LVEF at 12 months (OR: 2.1, 95% CI: 1.1-4.3, p = 0.035). Moreover, low sIL-1R2 levels were associated with an increased risk of having an adverse clinical event during the first 12 months after AMI [hazard ratio (HR): 2.5, 95% CI: 1.0-6.1, p = 0.039]. Conclusions: Low levels of circulating sIL-1R2 were associated with impaired recovery of LV function and adverse clinical outcomes in AMI patients. These findings might contribute to understanding the important role of sIL-1R2 in postinfarction inflammation.

7.
Mikrochim Acta ; 186(6): 353, 2019 05 16.
Article in English | MEDLINE | ID: mdl-31098674

ABSTRACT

The authors describe the syntheses and application of glutathione-capped gold nanoclusters (AuNCs) with thermoresponsive properties. The AuNCs have excitation/emission maxima at 430/610 nm and the bright redfluorescence changes along with the temperature in the range from 0 to 90 °C which covers the normal temperature range of living cells. In the range of physiological temperatures (35-42 °C), the temperature resolution is 0.73 °C. The AuNCs display excellent colloidal stability and biocompatibility. They were used for fluorometric temperature detection and imaging of hepatic stellate cells. With such attractive features, the AuNCs are quite promising luminescence nanothermometers. Graphical abstract Schematic presentation of the fluorescence of glutathione-capped gold nanoclusters (AuNCs) as nanothermometers in living cells. The AuNCs have excitation/emission maxima at 430/610 nm and the red fluorescence changes with temperature in a wide range of 0 to 90 °C which covers the normal temperature of living cells.


Subject(s)
Fluorometry , Gold/chemistry , Metal Nanoparticles/chemistry , Nanotechnology , Optical Imaging , Temperature , Cell Survival , Cells, Cultured , Fluorometry/instrumentation , Humans , Infrared Rays , Nanotechnology/instrumentation
9.
Adv Exp Med Biol ; 1096: 99-115, 2018.
Article in English | MEDLINE | ID: mdl-30324350

ABSTRACT

Prostate cancer (PCa) is the most common type of cancer in men with high morbidity and mortality. However, the current treatment with drugs often leads to chemotherapy resistance. It is known that the multi-disciplines research on molecular imaging is very helpful for early diagnosing, staging, restaging and precise treatment of PCa. In the past decades, the tumor-specific targeted drugs were developed for the clinic to treat prostate cancer. Among them, the emerging nanotechnology has brought about many exciting novel diagnosis and treatments systems for PCa. Nanotechnology can greatly enhance the treatment activity of PCa and provide novel theranostics platform by utilizing the unique physical/chemical properties, targeting strategy, or by loading with imaging/therapeutic agents. Herein, this chapter focuses on state-of-art advances in imaging and diagnosing PCa with nanomaterials and highlights the approaches used for functionalization of the targeted biomolecules, and in the treatment for various aspects of PCa with multifunctional nanoparticles, nanoplatforms and nanodelivery system.


Subject(s)
Nanoparticles , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/therapy , Drug Delivery Systems , Humans , Male , Nanotechnology
10.
Mikrochim Acta ; 185(4): 218, 2018 03 12.
Article in English | MEDLINE | ID: mdl-29594600

ABSTRACT

A nanoprobe is described for the ratiometric fluorometric determination of sulfite ions. Upconversion nanoparticles (UCNPs) of the type ß-NaYF4:Yb(III),Er(III),Tm(III) were covalently modified with the molecular probe HIAN which is a hydroxynaphthalimide fluorophore modified with a (cationic) indolinium moiety. Under excitation at 980 nm, the green emission of the UCNPs (peaking at 543 nm) is almost totally quenched, while the NIR emission (peaking at 802 nm) remains unaffected. In the presence of sulfite or bisulfite (hydrogen sulfite), the green fluorescence is restored and can be visually observed. A ratiometric method was worked out by measurement of the ratio of the green and NIR emissions. The analytical range extends from 10 to 250 µM, the limit of detection is 0.14 µM, and the assay can be performed within 40 s. Graphical abstract Based on the use of a molecular probe for sulfite and hydrogen sulfite, and by exploiting an inner filter effect (IFE), an assay for sulfite/hydrogen sulfite was developed by using upconversion nanoparticles (UCNPs). Addition reaction of sulfite/bisulfite with the material results in weakened IFE and enhanced green fluorescence of the UCNPs at excitation/emission wavelengths of 980/543 nm.

11.
Anal Chem ; 89(18): 10085-10093, 2017 09 19.
Article in English | MEDLINE | ID: mdl-28828856

ABSTRACT

Specific detection or imaging protein has high potential to contribute greatly to medical diagnosis, biological research, and therapeutic applications. The level of human serum albumin (HSA) in blood is related to a variety of diseases and thus serves as an important biomarker for fast clinical diagnosis. Here we report the use of aggregation-induced emission (AIE) based supramolecular assembly to design biomolecular responsive smart organic nanomaterials for detection protein HSA. The designed nanoprobes were aggregates of small molecules and silent in fluorescence, but in the presence of HSA they disassembled and produced a clear turn-on fluorescent signal. Of a small library of nanoprobes constructed for HSA detection, structure-optical signaling and screening studies revealed that nanoprobe 7 is the most efficient one. Mechanism studies showed that nanoprobe 7 was bonded with Site I of HSA through the multiple noncovalent interactions. The resultant restriction of intramolecular rotation of nanoprobe 7 in the hydrophobic cavity of HSA induced fluorescent emission, which was validated by competitive binding assays and molecular docking. More importantly, nanoprobe 7 was successfully applied to recognize and quantify HSA in human serum samples. This study demonstrates nanoprobe 7 is a promising tool for clinical real and fast detection of HSA and thus may find many applications, and the molecular assembly based on AIE also opens a new avenue for designing smart nanomaterials for the sensitive and selective detection for varied analytes.


Subject(s)
Fluorescent Dyes/chemistry , Nanostructures/chemistry , Serum Albumin, Human/analysis , Fluorescence , Fluorescent Dyes/chemical synthesis , Humans , Hydrophobic and Hydrophilic Interactions
12.
Org Biomol Chem ; 15(20): 4375-4382, 2017 May 23.
Article in English | MEDLINE | ID: mdl-28474717

ABSTRACT

Sulfur dioxide (SO2) is a widely distributed air pollutant, and humans can easily be exposed to sulfite by inhaling SO2, thus inducing respiratory responses and diseases. Hence, to develop a rapid, sensitive and selective method for detection of sulfites is of great importance. Herein, we designed and synthesized a novel tetraphenyl imidazole compound TIBM with aggregation-induced emission enhancement (AIEE). TIBM can self-assemble into well-organized nanoparticles and is reported as an excellent probe for detection of sulfite with high selectivity and sensitivity. The nanoprobe performed very well for the detection of sulfite with an ultrafast detection time (15 s) and an ultralow detection limit (7.4 nM), which is superior to most of the reported probes. Moreover, the nanoprobe was successfully used to detect sulfite in food samples with a favorable accuracy. In addition, we developed paper-based devices for point-of-care detection of sulfite with naked eyes. Furthermore, due to its high water solubility, cell membrane permeability and good biocompatibility, the nanoproboe was further applied to detect sulfite in living systems. This study may offer some helpful insights for designing other AIE-based fluorescent nanosensors for various analytes.


Subject(s)
Fluorescent Dyes/chemistry , Food Analysis/methods , Food Contamination/analysis , Nanoparticles/chemistry , Optical Imaging/methods , Sulfites/analysis , Benzylidene Compounds , Cell Line, Tumor , Cell Membrane Permeability , Fluorescence , Fluorescent Dyes/chemical synthesis , Humans , Hydrogen-Ion Concentration , Imidazoles , Molecular Structure , Nitriles , Particle Size , Quantum Theory
13.
Molecules ; 21(9)2016 Aug 31.
Article in English | MEDLINE | ID: mdl-27589715

ABSTRACT

Characterization of the chemical environment, movement, trafficking and interactions of proteins in live cells is essential to understanding their functions. Labeling protein with functional molecules is a widely used approach in protein research to elucidate the protein location and functions both in vitro and in live cells or in vivo. A peptide or a protein tag fused to the protein of interest and provides the opportunities for an attachment of small molecule probes or other fluorophore to image the dynamics of protein localization. Here we reviewed the recent development of no-wash small molecular probes for photoactive yellow protein (PYP-tag), by the means of utilizing a quenching mechanism based on the intramolecular interactions, or an environmental-sensitive fluorophore. Several fluorogenic probes have been developed, with fast labeling kinetics and cell permeability. This technology allows quick live-cell imaging of cell-surface and intracellular proteins without a wash-out procedure.


Subject(s)
Bacterial Proteins , Halorhodospira halophila , Photoreceptors, Microbial , Staining and Labeling/methods , Animals , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Halorhodospira halophila/chemistry , Halorhodospira halophila/genetics , Humans , Microscopy, Fluorescence , Photoreceptors, Microbial/chemistry , Photoreceptors, Microbial/genetics
14.
Analyst ; 140(6): 1814-6, 2015 Mar 21.
Article in English | MEDLINE | ID: mdl-25652214

ABSTRACT

A new ESIPT dye of benzothiazole with a conjugative electron acceptor was discovered and synthesized. Due to its unique NIR keto emission and a large Stokes shift, it was used to develop a fluorescent probe for sensitive and selective detection of hydrogen sulfide.


Subject(s)
Benzothiazoles/chemistry , Fluorescent Dyes/chemistry , Hydrogen Sulfide/analysis , Spectrometry, Fluorescence
15.
Int J Pharm ; 656: 124074, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38565406

ABSTRACT

Tacrolimus (FK506) is an effective therapeutic for transplant rejection in clinical practice, primarily inhibiting rejection by suppressing the activation and proliferation of allogeneic T cells in the lymph nodes (LNs). However, conventional administration methods face challenges in directly delivering free FK506 to the LNs. In this study, we introduce a novel LN-targeted delivery system based on mesoporous silica nanoparticles (MSNs-FK506-MECA79). These particles were designed to selectively target high endothelial venules in LNs; this was achieved through surface modification with MECA79 antibodies. Their mean size and zeta potential were 201.18 ± 5.98 nm and - 16.12 ± 0.36 mV, respectively. Our findings showed that MSNs-FK506-MECA79 could accumulate in LNs and increase the local concentration of FK506 from 28.02 ± 7.71 ng/g to 123.81 ± 76.76 ng/g compared with the free FK506 treatment group. Subsequently, the therapeutic efficacy of MSNs-FK506-MECA79 was evaluated in a skin transplantation model. The treatment with MSNs-FK506-MECA79 could lead to a decrease in the infiltration of T cells in the grafts, a reduction in the grade of rejection, and a significant prolongation of survival. Consequently, this study presents a promising strategy for the active LN-targeted delivery of FK506 and improving the immunotherapeutic effects on transplant rejection.


Subject(s)
Graft Rejection , Immunosuppressive Agents , Lymph Nodes , Nanoparticles , Silicon Dioxide , Tacrolimus , Tacrolimus/administration & dosage , Tacrolimus/chemistry , Silicon Dioxide/chemistry , Graft Rejection/prevention & control , Graft Rejection/immunology , Animals , Lymph Nodes/drug effects , Lymph Nodes/immunology , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/chemistry , Immunosuppressive Agents/pharmacology , Porosity , Mice, Inbred BALB C , Skin Transplantation/methods , Male , Mice , Mice, Inbred C57BL , Drug Delivery Systems/methods , Drug Carriers/chemistry
16.
Int J Cardiol ; 405: 131946, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38460732

ABSTRACT

BACKGROUND: Prior research underscores the significant impact of remnant cholesterol (RC) on stroke occurrence due to its proatherogenic and proinflammatory traits. This study aims to explore diverse risks of new-onset stroke associated with RC, considering distinct inflammation levels in the middle-aged and senior population in China. METHODS: We analyzed 6509 participants from the China Health and Retirement Longitudinal Study (CHARLS) across four waves (2011-2018). We employed a multivariable Cox proportional hazards regression model, incorporated restricted cubic spline techniques, and conducted sensitivity analyses to evaluate the association among RC, high-sensitivity C-reactive protein (hsCRP), and the risk of new-onset stroke. RESULTS: Over 7 years, 540 new-onset strokes occurred. Individuals in the highest quartile of RC levels exhibited a heightened risk of new-onset stroke, with a multivariable-adjusted hazard ratio (HR) peaking at 1.50 (95% confidence interval 1.12-2.00, P for trend = 0.021), showing a non-linear correlation (P nonlinearity = 0.049). High hsCRP alone had an adjusted HR of 1.10 (95% CI 0.87-1.39), compared to 1.40 (95% CI 1.00-1.96) for high RC alone. Additionally, concurrent high RC and hsCRP showed an adjusted HR of 1.43 (95% CI 1.05-1.96). Consistency persisted across various hsCRP thresholds, after adjusting for additional parameters, or excluding chronic diseases in the primary model, reinforcing result robustness. CONCLUSION: Our findings reveal a substantial and non-linear association between higher baseline RC levels and an elevated risk of new-onset stroke. Moreover, elevated levels of both RC and hsCRP jointly pose the highest risk for new-onset stroke, surpassing the risk associated with each factor individually.


Subject(s)
Cholesterol , Inflammation , Stroke , Humans , Male , Female , China/epidemiology , Longitudinal Studies , Middle Aged , Aged , Stroke/epidemiology , Stroke/blood , Inflammation/blood , Inflammation/epidemiology , Cholesterol/blood , Retirement , Risk Factors , Biomarkers/blood , Follow-Up Studies
17.
Heliyon ; 10(2): e24203, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38312645

ABSTRACT

T cells serve a pivotal role in the rejection of transplants, both by directly attacking the graft and by recruiting other immune cells, which intensifies the rejection process. Therefore, monitoring T cells becomes crucial for early detection of transplant rejection, while targeted drug delivery specifically to T cells can significantly enhance the effectiveness of rejection therapy. However, regulating the activity of T cells within transplanted organs is challenging, and the prolonged use of immunosuppressive drugs is associated with notable side effects and complications. Functionalized nanoparticles offer a potential solution by targeting T cells within transplants or lymph nodes, thereby reducing the off-target effects and improving the long-term survival of the graft. In this review, we will provide an overview of recent advancements in T cell-targeted imaging molecular probes for diagnosing transplant rejection and the progress of T cell-regulating nanomedicines for treating transplant rejection. Additionally, we will discuss future directions and the challenges in clinical translation.

18.
Adv Sci (Weinh) ; 11(26): e2309907, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38696589

ABSTRACT

Myocardial ischemia/reperfusion injury (MIRI) is the leading cause of irreversible myocardial damage. A pivotal pathogenic factor is ischemia/reperfusion (I/R)-induced cardiomyocyte ferroptosis, marked by iron overload and lipid peroxidation. However, the impact of lipid droplet (LD) changes on I/R-induced cardiomyocyte ferroptosis is unclear. In this study, an aggregation-induced emission probe, TPABTBP is developed that is used for imaging dynamic changes in LD during myocardial I/R-induced ferroptosis. TPABTBP exhibits excellent LD-specificity, superior capability for monitoring lipophagy, and remarkable photostability. Molecular dynamics (MD) simulation and super-resolution fluorescence imaging demonstrate that the TPABTBP is specifically localized to the phospholipid monolayer membrane of LDs. Imaging LDs in cardiomyocytes and myocardial tissue in model mice with MIRI reveals that the LD accumulation level increase in the early reperfusion stage (0-9 h) but decrease in the late reperfusion stage (>24 h) via lipophagy. The inhibition of LD breakdown significantly reduces the lipid peroxidation level in cardiomyocytes. Furthermore, it is demonstrated that chloroquine (CQ), an FDA-approved autophagy modulator, can inhibit ferroptosis, thereby attenuating MIRI in mice. This study describes the dynamic changes in LD during myocardial ischemia injury and suggests a potential therapeutic target for early MIRI intervention.


Subject(s)
Disease Models, Animal , Ferroptosis , Lipid Droplets , Myocardial Reperfusion Injury , Myocytes, Cardiac , Animals , Mice , Myocytes, Cardiac/metabolism , Myocardial Reperfusion Injury/metabolism , Lipid Droplets/metabolism , Male , Molecular Dynamics Simulation , Lipid Peroxidation
19.
Colloids Surf B Biointerfaces ; 234: 113680, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38101143

ABSTRACT

Myocardial ischemia-reperfusion injury (MIRI) is a widely recognized cardiovascular disease that significantly impacts the prognosis of patients undergoing myocardial infarction recanalization. This condition can be fatal and involves complex pathophysiological mechanisms. Early diagnosis of MIRI is crucial to minimize myocardial damage and reducing mortality. Based on the inherent relationship between platelets and MIRI, we developed biomimetic microbubbles coated with platelet membrane (MB-pla) for early identification of MIRI. The MB-pla were prepared through a recombination process involving platelet membrane obtained from rat whole blood and phospholipids, blended in appropriate proportions. By coating the microbubbles with platelet membrane, MB-pla acquired various adhesion molecules, thereby gaining the capability to selectively adhere to damaged endothelial cells in the context of MIRI. In vitro experiments demonstrated that MB-pla exhibited remarkable targeting characteristics, particularly toward type IV collagen and human umbilical vein endothelial cells that had been injured through hypoxia/reoxygenation procedures. In a rat model of MIRI, the signal intensity produced by MB-pla was notably higher than that of control microbubbles. These findings were consistent with results obtained from fluorescence imaging of isolated hearts and immunofluorescence staining of tissue sections. In conclusion, MB-pla has great potential as a non-invasive early detection method for MIRI. Furthermore, this approach can potentially find application in other conditions involving endothelial injury in the future.


Subject(s)
Myocardial Reperfusion Injury , Humans , Rats , Animals , Myocardial Reperfusion Injury/diagnostic imaging , Microbubbles , Biomimetics , Endothelial Cells , Early Diagnosis
20.
Adv Healthc Mater ; 12(9): e2202420, 2023 04.
Article in English | MEDLINE | ID: mdl-36575111

ABSTRACT

As macrophage infiltration is significantly related to the progression of inflammatory bowel disease (IBD), monitoring the macrophages is a valuable strategy for IBD diagnosis. However, owing to the harsh physiological environment of the gastrointestinal tract and enzymatic degradation, the development of orally administrable imaging probes for tracking macrophages remains a considerable challenge. Accordingly, herein, an orally administrable aggregation-induced emission biomimetic probe (HBTTPIP/ß-glucan particles [GPs]) is developed for tracing macrophages; HBTTPIP/GPs can diagnose and alleviate dextran sulfate sodium (DSS)-induced colonic inflammation and self-report the treatment efficiency. The fluorophore HBTTPIP can effectively aggregate in GPs, restricting intramolecular rotation and activating the fluorescence of HBTTPIP. After being orally administrated, HBTTPIP/GPs are phagocytosed by intestinal macrophages, which then migrate to colonic lesions, enabling non-invasive monitoring of the severity of IBD via in vivo fluorescence imaging. Notably, oral HBTTPIP/GPs ameliorate DSS-induced IBD by inhibiting the expressions of pro-inflammatory factors and improving colonic mucosal barrier function. Furthermore, these HBTTPIP/GPs realize self-feedback of the therapeutic effects of GPs on DSS-induced colitis. The oral biomimetic probe HBTTPIP/GPs reported herein provide a novel theranostic platform for IBD, integrating non-invasive diagnosis of IBD in situ and the corresponding treatment.


Subject(s)
Colitis , Inflammatory Bowel Diseases , Humans , Animals , Mice , Dextran Sulfate/pharmacology , Bionics , Cytokines/metabolism , Inflammatory Bowel Diseases/chemically induced , Inflammatory Bowel Diseases/diagnostic imaging , Inflammatory Bowel Diseases/drug therapy , Colitis/chemically induced , Colitis/diagnostic imaging , Colitis/drug therapy , Colon/diagnostic imaging , Colon/metabolism , Mice, Inbred C57BL , Disease Models, Animal
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