Kidney-type glutaminase is a biomarker for the diagnosis and prognosis of hepatocellular carcinoma: a prospective study.

PURPOSE: The pathological diagnosis and prognosis prediction of hepatocellular carcinoma (HCC) is challenging due to the lack of specific biomarkers. This study aimed to validate the diagnostic and prognostic efficiency of Kidney-type glutaminase (GLS1) for HCC in prospective cohorts with a large sample size. METHODS: A total of 1140 HCC patients were enrolled in our prospective clinical trials. Control cases included 114 nontumour tissues. The registered clinical trial (ChiCTR-DDT-14,005,102, chictr.org.cn) was referred to for the exact protocol. GLS1 immunohistochemistry was performed on the whole tumour section. The diagnostic and prognostic performances of GLS1 was evaluated by the receiver operating characteristic curve and Cox regression model. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, Youden index, and area under the curve of GLS1 for the diagnosis of HCC were 0.746, 0.842, 0.979, 0.249, 0.588, and 0.814, respectively, which could be increased to 0.846, 0.886, 0.987,0.366, 0.732, and 0.921 when combined with glypican 3 (GPC3) and alpha-fetoprotein (AFP), indicating better diagnostic performance. Further, we developed a nomogram with GPC3 and GLS1 for identifying HCC which showed good discrimination and calibration. GLS1 expression was also related with age, T stage, TNM stage, Edmondson-Steiner grade, microvascular invasion, Ki67, VEGFR2, GPC3, and AFP expression in HCC. GLS1 expression was negatively correlated with disease-free survival (P < 0.001) probability of patients with HCC. CONCLUSIONS: It was validated that GLS1 was a sensitive and specific biomarker for pathological diagnosis of HCC and had prognostic value, thus having practical value for clinical application.

LeSAM: Adapt Segment Anything Model for medical lesion segmentation.

The Segment Anything Model (SAM) is a foundational model that has demonstrated impressive results in the field of natural image segmentation. However, its performance remains suboptimal for medical image segmentation, particularly when delineating lesions with irregular shapes and low contrast. This can be attributed to the significant domain gap between medical images and natural images on which SAM was originally trained. In this paper, we propose an adaptation of SAM specifically tailored for lesion segmentation termed LeSAM. LeSAM first learns medical-specific domain knowledge through an efficient adaptation module and integrates it with the general knowledge obtained from the pre-trained SAM. Subsequently, we leverage this merged knowledge to generate lesion masks using a modified mask decoder implemented as a lightweight U-shaped network design. This modification enables better delineation of lesion boundaries while facilitating ease of training. We conduct comprehensive experiments on various lesion segmentation tasks involving different image modalities such as CT scans, MRI scans, ultrasound images, dermoscopic images, and endoscopic images. Our proposed method achieves superior performance compared to previous state-of-the-art methods in 8 out of 12 lesion segmentation tasks while achieving competitive performance in the remaining 4 datasets. Additionally, ablation studies are conducted to validate the effectiveness of our proposed adaptation modules and modified decoder.

The value of apparent diffusion coefficient values in predicting Gleason grading of low to intermediate-risk prostate cancer.

OBJECTIVES: To investigate the diagnostic performance of the apparent diffusion coefficient (ADC) for low to intermediate-risk prostate cancer (PCa), as well as its correlation with the prognostic Gleason score (GS). MATERIALS AND METHODS: Retrospective analysis of MRI images and relevant clinical data from patients with prostate disease. The differences in ADC between different GS groups were compared, and the efficacy of ADC in PCa diagnosis were analyzed. Furthermore, the diagnostic performance of the mean ADC (ADCmean) and minimum ADC (ADCmin) values was compared. RESULTS: There were 1414 patients with 1631 lesions. In terms of GS, both ADCmin and ADCmean values of the GS 4 + 3 group were significantly lower than those of the GS 3 + 4 group, GS 3 + 3 group, and the benign group, with all differences being statistically significant (p < 0.01). The AUC values for diagnosing PCa based on ADCmin and ADCmean were 0.914 and 0.944, respectively. The corresponding diagnostic thresholds were 0.703 × 10-3 mm2/s for ADCmin and 0.927 × 10-3 mm2/s for ADCmean. The magnitudes of ADCmin and ADCmean values exhibited a negative correlation with GS values (ρ = -0.750, p < 0.001; ρ = -0.752, p < 0.001). CONCLUSIONS: ADC values demonstrate an inverse relationship with the invasiveness of PCa, indicating that higher invasiveness is associated with lower ADC values. Additionally, ADC values exhibit high diagnostic potential, sensitivity, and specificity for distinguishing between GS 3 + 4 and GS 4 + 3 lesions. Moreover, the diagnostic value of ADCmean is even more significant, highlighting its crucial role in the diagnosis of low to intermediate-risk PCa. CRITICAL RELEVANCE STATEMENT: ADC values are a valuable tool for distinguishing different levels of aggressiveness in PCa. They help in the preoperative assessment of the biological characteristics of PCa, allowing clinicians to develop personalized treatment strategies, effectively mitigating the risk of unnecessary interventions. KEY POINTS: The preoperative GS is crucial for planning the clinical treatment of PCa. The invasiveness of PCa is inversely correlated with ADC values. ADC values play a crucial role in the accurate preoperative evaluation of low to intermediate-risk PCa, thus aiding clinicians in developing tailored treatment plans.

Primary pulmonary intravascular large B­cell lymphoma misdiagnosed as pneumonia: Four case reports and a literature review.

Primary pulmonary intravascular large B-cell lymphoma (IVLBCL) is a rare, malignant extranodal lymphoma. It is difficult to diagnose clinically as it requires a combination of clinical and computed tomography (CT) evaluations, as well as laboratory and pathological examinations. In the present study, 4 cases of primary pulmonary IVLBCL were reviewed. The patients' ages ranged from 60 to 69 years old. Of the 4 patients, 3 developed progressive dyspnea on exertion and intermittent fever. Other symptoms included coughing, chest tightness and weight loss. Laboratory data indicated that all patients had anemia, thrombocytopenia, hypoxemia, a markedly high serum lactate dehydrogenase level, elevated erythrocyte sedimentation rate and increased C-reactive protein. CT demonstrated increased attenuation in bilateral lung parenchyma, especially in the upper lobes, with multiple ground-glass opacities associated with small nodules in these patients. Initially, all 4 patients were misdiagnosed with pneumonia. However, none of them responded to anti-inflammatory treatments. The pathologies of all patients were confirmed using lung biopsy. Only 1 patient received regular combination chemotherapy. Based on the observations of the present study, a standard regimen for lymphoma treatment may result in a notable clinical response.

Transfection of clMagR/clCry4 imparts MR-T2 imaging contrast properties to living organisms (E. coli) in the presence of Fe3+ by endogenous formation of iron oxide nanoparticles.

Rapid development of medical imaging, such as cellular tracking, has increased the demand for "live" contrast agents. This study provides the first experimental evidence demonstrating that transfection of the clMagR/clCry4 gene can impart magnetic resonance imaging (MRI) T2-contrast properties to living prokaryotic Escherichia coli (E. coli) in the presence of Fe3+ through the endogenous formation of iron oxide nanoparticles. The transfected clMagR/clCry4 gene markedly promoted uptake of exogenous iron by E. coli, achieving an intracellular co-precipitation condition and formation of iron oxide nanoparticles. This study will stimulate further exploration of the biological applications of clMagR/clCry4 in imaging studies.

Some Preliminary Results to Eradicate Leukemic Cells in Extracorporeal Circulation by Actuating Doxorubicin-Loaded Nanochains of Fe3O4 Nanoparticles.

Leukemia is a non-solid cancer which features the malignant proliferation of leukocytes. Excessive leukocytes of lesions in peripheral blood will infiltrate organs, resulting in intumescence and weakening treatment efficiency. In this study, we proposed a novel approach for targeted clearance of the leukocytes in the peripheral blood ex vivo, which employed magnetic nanochains to selectively destroy the leukocytes of the lesions. The nanochains were doxorubicin-loaded nanochains of Fe3O4 nanoparticles which were fabricated by the solvent exchange method combined with magnetic field-directed self-assembly. Firstly, the nanochains were added into the peripheral blood during extracorporeal circulation and subjected to a rotational magnetic field for actuation. The leukocytes of the lesion were then conjugated by the nanochains via folic acid (FA) targeting. Finally, the rotational magnetic field actuated the nanochains to release the drugs and effectively damage the cytomembrane of the leukocytes. This strategy was conceptually shown in vitro (K562 cell line) and the method's safety was evaluated in a rat model. The preliminary results demonstrate that the nanochains are biocompatible and suitable as drug carriers, showing direct lethal action to the leukemic cells combined with a rotational magnetic field. More importantly to note is that the nanochains can be effectively kept from entry into the body. We believe this extracorporeal circulation-based strategy by activating nanochains magnetically could serve as a potential method for leukemia treatment in the future.

Edge prior guided dictionary learning for quantitative susceptibility mapping reconstruction.

BACKGROUND: Compared with conventional magnetic resonance imaging methods, the quantitative magnetic susceptibility mapping (QSM) technique can quantitatively measure the magnetic susceptibility distribution of tissues, which has an important clinical application value in the investigations of brain micro-bleeds, Parkinson's, and liver iron deposition, etc. However, the quantitative susceptibility mapping algorithm is an ill-posed inverse problem due to the near-zero value in the dipole kernel, and high-quality QSM reconstruction with effective streaking artifact suppression remains a challenge. In recent years, the performance of sparse representation has been well validated in improving magnetic resonance image (MRI) reconstruction. METHODS: In this study, by incorporating feature learning into sparse representation, we propose an edge prior guided dictionary learning-based reconstruction method for the dipole inversion in quantitative susceptibility mapping reconstruction. The structure feature dictionary relies on magnitude images for susceptibility maps have similar structures with magnitude images, and this structure feature dictionary and edge prior information are used in the dipole inversion step. RESULTS: The performance of the proposed algorithm is assessed through in vivo human brain clinical data, leading to high-quality susceptibility maps with improved streaking artifact suppression, structural recovery, and quantitative metrics. CONCLUSIONS: The proposed edge prior guided dictionary learning method for dipole inversion in QSM achieves improved performance in streaking artifacts suppression, structural recovery and deep gray matter reconstruction.

High-density thrombus and maximum transverse diameter on multi-spiral computed tomography angiography combine to predict abdominal aortic aneurysm rupture.

Objective: We attempted to measure maximum transverse diameter (MTD) of and CT values of ILT by using multi-spiral computed tomography angiography (MSCTA) to investigate the predictive value of MTD with different CT values of thrombus on the risk of AAA rupture. Methods: Forty-five intact abdominal aortic aneurysms (IAAA) and 17 ruptured abdominal aortic aneurysms (RAAA) were included in this study. MTD and CT values in their planes were measured from MSCTA images and aneurysm lumen and thrombus volumes were calculated for the range of different CT values. Results: The median of maximum CT value of thrombus at the plane of MTD was higher in RAAA (107.0 HU) than the median in IAAA (84.5 HU) (P < 0.001). Univariate logistic regression analysis showed that the maximum CT value was a risk factor for RAAA (P < 0.001). It was further found that the area under the ROC curve for thrombus maximum CT value in the MTD plane to predict RAAA was 0.848 (P < 0.001), with a cut-off value of 97.5 HU, a sensitivity of 82.35%, and a specificity of 84.44%. And the MTD of the abnormal lumen combined with the maximum CT value at its plane predicted RAAA with an area under the ROC curve of 0.901, a sensitivity of 76.47%, and a specificity of 97.78%. The further analysis of thrombus volume in the range of different CT value showed that median thrombus volume in RAAA in the range of 30 HU~150 HU was 124.2 cm3 which was higher than the median of 81.4 cm3 in IAAA (P = 0.005). To exclude confounding factors (aneurysm volume), we calculated the standardized thrombus (ILT volume/total aneurysm volume), and the thrombus volume in the range of 30 HU~150 HU in RAAA was positively correlated with the standardized thrombus volume (ρ = 0.885, P < 0.001), while the thrombus volume in the range of -100 HU~30 HU was not correlated with it (ρ = 0.309, P = 0.228). Conclusions: High-density ILT shown on MSCTA in AAAs is associated with aneurysm rupture, and its maximum transverse diameter combined with the maximum CT value in its plane is a better predictor of RAAA.

Deep learning-based framework for segmentation of multiclass rib fractures in CT utilizing a multi-angle projection network.

PURPOSE: Clinical rib fracture diagnosis via computed tomography (CT) screening has attracted much attention in recent years. However, automated and accurate segmentation solutions remain a challenging task due to the large sets of 3D CT data to deal with. Down-sampling is often required to face computer constraints, but the performance of the segmentation may decrease in this case. METHODS: A new multi-angle projection network (MAPNet) method is proposed for accurately segmenting rib fractures by means of a deep learning approach. The proposed method incorporates multi-angle projection images to complementarily and comprehensively extract the rib characteristics using a rib extraction (RE) module and the fracture features using a fracture segmentation (FS) module. A multi-angle projection fusion (MPF) module is designed for fusing multi-angle spatial features. RESULTS: It is shown that MAPNet can capture more detailed rib fracture features than some commonly used segmentation networks. Our method achieves a better performance in accuracy (88.06 ± 6.97%), sensitivity (89.26 ± 5.69%), specificity (87.58% ± 7.66%) and in terms of classical criteria like dice (85.41 ± 3.35%), intersection over union (IoU, 80.37 ± 4.63%), and Hausdorff distance (HD, 4.34 ± 3.1). CONCLUSION: We propose a rib fracture segmentation technique to deal with the problem of automatic fracture diagnosis. The proposed method avoids the down-sampling of 3D CT data through a projection technique. Experimental results show that it has excellent potential for clinical applications.

Combined clinical features and MRI parameters for the prediction of VEGFR2 in hepatocellular carcinoma patients.

Purpose: To develop a prediction model for estimating the expression of vascular endothelial growth factor receptor 2 (VEGFR2) in hepatocellular carcinoma (HCC) patients using clinical features and the contrast-enhanced MRI Liver Imaging Reporting and Data System (LI-RADS). Methods: A total of 206 HCC patients were subjected to preoperative contrast-enhanced MRI, radical resection, and VEGFR2 immunohistochemistry labeling. The intensity of VEGFR2 expression was used to split patients into either the positive group or the negative group. For continuous data, the Mann-Whitney U test was employed, and for categorical variables, the χ2 test was utilized. Results: VEGFR2-positivity was identified in 41.7% (86/206) of the patients. VEGFR2-positive HCCs were confirmed by higher serum alpha-fetoprotein (AFP) levels, larger tumor dimensions (either on MRI or upon final pathology), and a higher LI-RADS score (all p < 0.001). LI-RADS scores and AFP levels were independent predictors for high VEGFR2 expression. These two parameters were used to establish a VEGFR2-positive risk nomogram, which was validated to possess both good discrimination and calibration. The area under the curve was 0.830 (sensitivity 83.6%, specificity 72.5%) and the mean absolute error was 0.021. The threshold probabilities ranged between 0.07 and 0.95, and usage of the model contributed net benefits. Conclusion: A nomogram including clinical features and contrast-enhanced MRI parameters was developed and was demonstrably effective at predicting VEGFR2 expression in HCC patients.

Triphasic dynamic contrast-enhanced computed tomography predictive model of benign and malignant risk of gallbladder occupying lesions.

Gallbladder occupying lesions are common diseases of biliary system. Among them, gallbladder cancer is difficult to diagnose due to the indistinguishable early symptoms, thus posing a great risk to the population. This study aims to establish a computed tomography (CT) prediction model for distinguishing benign and malignant lesions of gallbladder occupying lesions.The study included 211 patients with benign or malignant gallbladder occupying lesions who have taken resection in the Nanjing Drum Tower Hospital from January 2009 to December 2017. Clinical data collected includes age and sex; CT data includes tumor location, tumor maximum diameter, tumor form, venous phase portal venous CT value, abdominal aortic CT value, plain phase CT value, arterial phase CT value, venous phase CT value, delayed phase CT value, ΔCT1, ΔCT2, ΔCT3, ΔCT4, ΔCT5, ΔCT6, and ΔCT7. Calculation of odds ratio between benign and malignant gallbladder occupying lesions using single factor screening variables and multivariate logistic regression was done to establish a model and calculate the areas under receiver operating characteristic curves of the model.Multivariate logistic regression analysis showed that age, tumor maximum diameter, tumor form, venous phase portal venous CT value, ΔCT2, ΔCT4, and ΔCT6 are the main characteristic index for differential diagnosis of benign and malignant risk of gallbladder occupying lesions.Patients' age, tumor maximum diameter, tumor form, venous phase portal venous CT value, ΔCT2, ΔCT4, and ΔCT6 are independent risk factors for judging the benign and malignant of gallbladder occupying lesions. The model established exhibited a potential diagnostic value for distinguishing the malignant properties of gallbladder occupying lesions.

Specific, Non-Invasive, and Magnetically Directed Targeting of Magnetic Erythrocytes in Blood Vessels of Mice.

OBJECTIVE: Targeting in vivo has been a spotlight for precise medicine. Multiple strategies have been proposed for this issue. However, the efficiency of solely biochemical strategies currently remains to be improved. It has been thought that external field-guided targeting will be a beneficial supplement for the passive and the active targeting. METHODS: Here, we focused on the magnetic field-guided targeting of magnetized erythrocytes, discovering that a focused magnetic field can direct aggregation of magnetic erythrocytes into a specific region in vivo. RESULTS: The systematic investigation about the aggregates in cerebral vessels showed that the aggregates were isotropic and able to stably exist for six hours. The formation of cellular aggregates can alter echoing characteristic of the blood vessels meaning the vascular wall became more rigid. If the erythrocytes were repeatedly directed into aggregation in an identical region, a stable plaque of erythrocytes can form, which can mimic the process of thrombosis. SIGNIFICANCE: We believe these results will be beneficial to the development of novel engineered strategy for targeted delivery of drugs and modeling of vascular diseases.

Integration of immunogenic activation and immunosuppressive reversion using mitochondrial-respiration-inhibited platelet-mimicking nanoparticles.

Here, we developed platelet membranes (PM) as nano-carriers to co-encapsulate metformin (Met) and IR780 (PM-IR780-Met NPs). The resulting nano-carrier ensured a longer circulation lifetime and facilitated the greater accumulation of IR780 and Met in tumors owing to the active adhesion between PM and tumor cells. As a photodynamic therapy (PDT) agent, IR780 could effectively kill the tumor by producing toxic reactive singlet oxygen species (ROS), while the introduction of Met inhibited mitochondrial respiration and reduced tumor oxygen consumption, thereby evoking an oxygen-boosted PDT and propelling the immunogenic cell death (ICD)-based immunogenic pathway. Meanwhile, the reversed tumor hypoxia also impeded the myeloid derived suppressor cell (MDSC)-regulated immunosuppressive pathway. Finally, tremendous T cells were recruited and activated, providing a promising platform to eliminate the primary tumors and synchronously opening a new avenue for the effective ablation of tumor metastasis.

Assessments of proliferation capacity and viability of New Zealand rabbit peripheral blood endothelial progenitor cells labeled with superparamagnetic particles.

Magnetic resonance imaging (MRI) has proven to be effective in tracking the distribution of transplanted stem cells to target organs by way of labeling cells with superparamagnetic iron oxide particles (SPIO). However, the effect of SPIO upon labeled cells is still unclear on a cellular level. With this study, the proliferation and viability of New Zealand rabbit peripheral blood endothelial progenitor cells (EPCs) labeled with SPIO were evaluated and in vitro images were obtained using a 1.5 T MR scanner. Mononuclear cells (MNCs) were isolated from peripheral blood of the adult New Zealand rabbit and cultured in fibronectin-coated culture flasks, in which EPCs were identified from cell morphology, outgrowth characteristics, and internalization of DiI-Ac-LDL and binding to FITC-UEA I. EPCs were incubated with the self-synthesized poly-L-lysine-conjugated SPIO (PLL-SPIO) particles in a range of concentrations. The prevalence of iron-containing vesicles or endosomes in the cytoplasm of labeled cells was confirmed with Prussian blue staining and transmission electron microscopy. Tetrazolium salt (MTT) assay, cell apoptosis, and cycle detection were assessed to evaluate proliferation and function of various concentrations, magnetically labeled EPCs. The quantity of iron per cell was determined by atomic absorption spectrometry. The cells underwent MRI with different sequences. The result showed that rabbit EPCs were efficiently labeled with the home synthesized PLL-SPIO. There was found to be no statistically significant difference in the MTT values of light absorption measured on the third and fifth days. Between labeled and unlabeled cells, there were also no aberrations found in the cell cycles, apoptosis, or growth curves. The atomic absorption spectrophotometer showed that the intracellular content of Fe decreased as more time elapsed after labeling. The labeled EPCs demonstrated a loss of MRI signal intensity (SI) when compared with the SI of unlabeled cells. These signal changes (ASI) were visible when cells were labeled with more than 5 x 104/ml of SPIO. The change in SI corresponded to the amount of iron in the EPCs, which reached a maximum at T2*WI. These data demonstrate that EPCs from the peripheral blood of the New Zealand rabbit can be effectively labeled with self-synthesized PLL-SPIO with minimal effects on cell proliferation and activity. Magnetically labeled EPCs can be imaged at 1.5 T MR and can therefore be used as an MR tracker of implanted EPCs.

Self-generating oxygen enhanced mitochondrion-targeted photodynamic therapy for tumor treatment with hypoxia scavenging.

Tumor hypoxia is an important reason for the limited therapeutic efficacy of photodynamic therapy (PDT) because of the oxygen requirement of the therapeutic process. PDT consumes tissue oxygen and destroys tumor vasculature, further hampering its own efficacy in promoting tumor deterioration. Therefore, overcoming the photodynamic exacerbation of tumor hypoxia is urgent. Methods: Herein, we report a photodynamic nanoparticle with sustainable hypoxia remission skills by both intratumoral H2O2 catalysis and targeted mitochondrial destruction. The Mn3O4@MSNs@IR780 nanoparticles are formed by absorbing a photosensitizer (IR780) into 90 nm mesoporous silica nanoparticles (MSNs) and capping the surface pores with 5 nm Mn3O4 nanoparticles. Results: These Mn3O4 nanoparticles can accumulate in tumors and respond to the H2O2-enriched tumor microenvironment by decomposing and catalyzing H2O2 into O2. Afterwards, IR780 is released and activated, spontaneously targeting the mitochondria due to its natural mitochondrial affinity. Under laser irradiation, this self-generated oxygen-enhanced PDT can destroy mitochondria and inhibit cell respiration, resulting in sustainable hypoxia remission in tumor tissues and consequently enhancing the therapeutic outcome. In vitro experiments suggest that Mn3O4@MSNs@IR780 exhibited highly mitochondrion-targeted properties and could sustainably inhibit tumor hypoxia. Additionally, the highest photoacoustic signal of HbO2 with the lowest Hb was observed in tumors from mice after PDT, indicating that these nanoparticles can also prevent tumor hypoxia in vivo. Conclusion: Taken together, our study indicated a new approach for overcoming the sustainable hypoxia limitation in traditional PDT by targeted oxygen supplementation and mitochondria destruction.

Systematic Intracellular Biocompatibility Assessments of Superparamagnetic Iron Oxide Nanoparticles in Human Umbilical Cord Mesenchyme Stem Cells in Testifying Its Reusability for Inner Cell Tracking by MRI.

Until now, there is no effective method for tracking transplanted stem cells in human. Ruicun (RC) is a new ultra-small SPIONs agent that has been approved by China Food and Drug Administration for iron supplementation but not as a stem cell tracer in clinic. In this study, we demonstrated magnetic resonance imaging-based tracking of RC-labeled human umbilical cord derived mesenchymal stem cells (MSCs) transplanted to locally injured site of rat spinal cords. We then comprehensively evaluated the safety and quality of the RC-labeled MSCs under good manufacturing practicecompliant conditions, to investigate the feasibility of SPIONs for inner tracking in stem cell-based therapy (SCT). Our results showed that RC labeling at appropriate dose (200 µg/mL) did not have evident impacts on characteristics of MSCs in vitro, demonstrating safety, non-carcinogenesis, and non-tissue inflammation in vivo. The systematic assessments of intracellular biocompatibility indicated that the RC labeled MSCs met with mandatory requirements and standards for law-regulation systems regarding SCT, facilitating translation of cell-tracking technologies to clinical trials.

Soft mesoporous organosilica nanorods with gold plasmonic core for significantly enhanced cellular uptake.

Soft nanoparticles have attracted increasing attention in biomedical fields because of their unique biological behaviors such as long circulation and high cellular uptake. However, previously reported soft nanoparticles are generally spherical or torispherical in shape, and non-spherical soft nanoparticles are rarely reported because of the shape is thermodynamically unstable for typical soft materials (e.g., liposomes and micelles). Herein, soft mesoporous organosilica nanorods with gold plasmonic core protected with poly-ethylene imine (GNR@SMON/PEI) have been successfully synthesized, for the first time, by a dispersive-protection etching method, in which rod-like solid mesoporous organosilicas with gold nanorod are firstly shielded with PEI (GNR@MON/PEI) and then etched with aqueous NaOH solution. The prepared GNR@SMON/PEI inherits the rod morphology of the mother particle, showing wrinkled morphology and excellent dispersity thanks to the dispersive-protection effect of PEI. In addition, the GNR@SMON/PEI possesses a uniform size (174 × 105 nm), well-defined mesopores (3.9 nm), high surface area (355 m2/g) and large pore volume (0.35 m3/g). Notably, the soft GNR@SMON/PEI exhibits significantly lower Young's modulus (120.2 MPa) in contrast with the hard counterpart (361.4 MPa). Furthermore, after being decorated with hyaluronic acid (HA), the soft GNR@SMON/PEI-HA exhibits excellent in vitro and in vivo biocompatibility. The soft GNR@SMON/PEI-HA has achieved 3-fold cellular uptake efficiency in contrast with the hard one, indicating great potential for biomedical applications. Taken together, this work reports the controllable synthesis of a soft mesoporous nanorod with high cellular uptake efficiency, providing a vital strategy for the synthesis of non-spherical soft nanoparticles and a new nanoplatform for various biomedical applications in future.

MR tracking of magnetically labeled mesenchymal stem cells in rat kidneys with acute renal failure.

Stem cell transplantation is emerging as a potential treatment option for acute renal failure (ARF) because of its capability to regenerate tissues and organs. To better understand the mechanism of cell therapy, in vivo tracking cellular dynamics of the transplanted stem cells is needed. In the present study, in vivo monitored magnetically labeled mesenchymal stem cells (MSCs) were transplanted intravascularly into an ARF rat model using a conventional magnetic resonance imaging (MRI) system. Rat bone marrow MSCs were labeled with home synthesized Fe2O3-PLL, and labeled (n = 6) or unlabeled MSCs (n = 6) were injected into the renal arteries of the rats with ARF induced by the intramuscular injection of glycerol. Using the same technique, labeled MSCs were also injected into the rats assigned to a control group (n = 8). MR images of kidneys were obtained before injection of MSCs as well as immediately, 1, 3, 5, and 8 days afterwards. MR findings were analyzed and compared with histopathological and immunohistochemical results. These results showed that the rat MSCs were successfully labeled with the home synthesized Fe2O3-PLL. In both renal failure and intact rat models, the labeled MSCs demonstrated a loss of signal intensity in the renal cortex on T2*-weighted MR images, which was visible up to 8 days after transplantation. Histological analyses showed that most of the labeled MSCs that tested positive for Prussian blue staining were in glomerular capillaries, corresponding to the areas where a loss in signal intensity was observed in the MRI. A similar signal intensity decrease was not detected in the rats with unlabeled cells. These data demonstrate that the magnetically labeled MSCs in the rat model of ARF were successfully evaluated in vivo by a 1.5 T MRI system, showing that the mechanisms of stem cell therapy have great potential for future ARF treatment recipients.

[Magnetic resonance imaging of mesenchymal stem cells transplanted intravascularly in treatment of acute renal failure:in vivo experiment with rats].

OBJECTIVE: To evaluate the efficacy of in vivo magnetic resonance imaging (MRI) of mesenchymal stem cells (MSCs) injected intravascularly in treatment of acute renal failure (ARF) , and to investigate the changes of renal function and pathology of ARF after MSC transplantation. METHODS: Rat MSCs were isolated and labeled with Fe2O3-PLL in vitro. Thirty SD rats underwent intramuscular injection of glycerol so as to establish ARF models and then randomly divided into 3 equal groups: Group I undergoing injection of labeled MSCs into abdominal aorta via transcatheter, Group II injected with unlabelled MSCs, and Group III injected with normal saline as controls. MRI of kidney was conducted before injection, and 0.5 h, and 1, 2, and 5 days after injection. One and 2 days after the transplantation 3 rats from each group underwent MRI and extraction of blood samples from the abdominal aorta and then killed with their kidneys taken out, and 5 days after the rest rats were all killed after MRI with their kidneys taken out. Serum creatinine (Scr) and blood urea nitrogen (BUN) were examined so as to evaluate the renal function. Microscopy was conducted to observe the pathological changes. Prussian blue + CD68 antibody staining was performed to identify the labeled MSCs. RESULTS: MRI showed decrease of signal intensity in renal cortex on the T2 *-weighted MR images up to 5 days after transplantation. Histological analysis showed that most Prussian blue-positive cells were in the glomerular capillaries, corresponding to the areas where signal intensity decrease was observed by MRI. The Scr and BUN levels 2 and 5 days after the implantation of Group I were both lower than those of the control group, and there were not significant differences in the Scr and BUN levels between Groups I and II. Renal tubular injury scoring showed that the renal tubular injury was significantly lighter than that of the control group. CONCLUSION: 1.5-T MRI seems a good in vivo technique to monitor the magnetically labeled MSCs administered into the abdominal aorta of ARF animals, which are distributed in the glomerular capillaries in the early stage after transplantation. MSCs may promote the recovery of ARF.

[In vitro MR imaging of Fe2O3-arginine labeled heNOS gene modified endothelial progenitor cells].

OBJECTIVE: To explore the feasibility of in vitro magnetic resonance imaging on Fe2O3-arginine labeled heNOS gene modified endothelial progenitor cells (EPCs). METHODS: Fe2O3 was incubated with arginine to form Fe2O3-arginine complex. Rabbit peripheral blood mononuclear cells (MNCs) were isolated and EPCs were isolated by adherence method, expanded and modified with heNOS gene using Lipofectamine 2000. After 48 hours, genetically modified EPCs were incubated with Fe2O3-arginine for 24 hours. Intracellular iron was detected by Prussian blue stain. The expression of heNOS gene was detected by Western blot. MTT assay was used to evaluate cell survival and proliferation of Fe2O3-arginine labeled heNOS-EPCs. Flow cytometry was used to measure cell apoptosis. The cells underwent in vitro MR imaging with various sequences. RESULTS: Iron-containing intracytoplasmatic vesicles could be clearly observed with Prussian blue staining, and the labeling rate of labeled heNOS-EPCs were similar to that of labeled EPCs (around 100%). Survival and apoptosis rates obtained by MTT and flow cytometry analysis were similar among labeled heNOS-EPCs, labeled EPCs and unlabeled EPCs with Fe2O3-arginine. The signal intensity on MRI was equally decreased in labeled heNOS-EPCs and labeled EPCs compared with that in unlabeled cells. The percentage change in signal intensity (DeltaSI) was most significant on T2*WI and DeltaSI was significantly lower in cells labeled for 7 days than that labeled for 1 days. CONCLUSIONS: The heNOS gene can be successfully transfected into rabbit peripheral blood EPCs using Lipofectamine2000. The heNOS-EPCs can be labeled with Fe2O3-arginine without significant change in viability and proliferation capacity. The labeled heNOS-EPCs can be imaged with standard 1.5 T MR equipment. The degree of MR signal intensity may indirectly reflect the cell count, growth and division status.