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1.
Front Endocrinol (Lausanne) ; 14: 1241307, 2023.
Article in English | MEDLINE | ID: mdl-37732124

ABSTRACT

Background: Diabetes mellitus (DM) is a chronic disease that poses a serious risk of cardiovascular diseases. Therefore, early detection of impaired cardiac function with non-invasive myocardial imaging is critical for improving the prognosis of patients with DM. Purpose: This study aimed to assess the left ventricular (LV) function in patients with type 2 diabetes mellitus (T2DM) by non-invasive myocardial work technique. Materials and methods: In all, 67 patients with T2DM and 28 healthy controls were included and divided into a DM group and a control group. Two-dimensional dynamic images of apical three-chamber view, apical two-chamber view, and apical four-chamber view were collected from all subjects, consisting of at least three cardiac cycles. LV myocardial strain parameters, including global longitudinal strain (GLS) and peak strain dispersion (PSD), as well as myocardial work parameters, including global constructive work (GCW), global wasted work (GWW), global work index (GWI), and global work efficiency (GWE), were obtained and analyzed. Results: A total of 15 subjects were randomly selected to assess intra-observer and inter-observer consistency of myocardial work parameters and strain parameters, which showed excellent results (intra-class correlation coefficients: 0.856 - 0.983, P<0.001). Compared with the control group, the DM group showed significantly higher PSD (37.59 ± 17.18 ms vs. 27.72 ± 13.52 ms, P<0.05) and GWW (63.98 ± 43.63 mmHg% vs. 39.28 ± 25.67 mmHg%, P<0.05), and lower GWE (96.38 ± 2.02% vs. 97.72 ± 0.98%, P<0.001). Furthermore, the PSD was positively correlated with GWW (r = 0.565, P<0.001) and negatively correlated with GWE (r = -0.569, P<0.001). Conclusion: Uncoordinated LV myocardial strain, higher GWW, and lower GWE in patients with T2DM may serve as indicators for the early assessment of cardiac impairment in T2DM.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/complications , Ventricular Function, Left , Myocardium , Heart
2.
Echocardiography ; 40(6): 537-549, 2023 06.
Article in English | MEDLINE | ID: mdl-37178387

ABSTRACT

OBJECTIVES: To evaluate the left ventricular energy loss (EL), energy loss reserve (EL-r), and energy loss reserve rate in patients with mild coronary artery stenosis by using vector flow mapping (VFM) combined with exercise stress echocardiography. METHODS: A total of 34 patients (case group) with mild coronary artery stenosis and 36 sex and age matched patients (control group) without coronary artery stenosis according to coronary angiogram were prospectively enrolled. The total energy loss (ELt), basal segment energy loss (ELb), middle segment energy loss (ELm), apical segment energy loss (ELa), energy loss reserve (EL-r), and energy loss reserve rate were recorded in the isovolumic systolic period (S1), rapid ejection period (S2), slow ejection period (S3), isovolumic diastolic period (D1), rapid filling period (D2), slow filling period (D3), and atrial contraction period (D4). RESULTS: Compared with the control group, some of the EL in the resting case group were higher; some of the EL in the case group were lower after exercise, and those during D1 ELb and D3 ELb were higher. Compared with the resting state, the total EL and the EL within the time segment in the control group were higher after exercise, except during D2 ELb. In the case group, except for during D1 ELt, ELb and D2 ELb, the total and segmental EL of each phase was mostly higher after exercise (p < .05). Compared with the control group, most of the EL-r and EL reserve rates in the case group were lower (p < .05). CONCLUSION: The EL, EL-r, and energy loss reserve rate have a certain value in the evaluation of cardiac function in patients with mild coronary artery stenosis.


Subject(s)
Coronary Stenosis , Echocardiography, Stress , Humans , Systole , Diastole , Heart Ventricles/diagnostic imaging , Ventricular Function, Left
3.
Comput Intell Neurosci ; 2023: 1353965, 2023.
Article in English | MEDLINE | ID: mdl-36818578

ABSTRACT

Antinuclear antibodies (ANAs) testing is the main serological diagnosis screening test for autoimmune diseases. ANAs testing is conducted principally by the indirect immunofluorescence (IIF) on human epithelial cell-substrate (HEp-2) protocol. However, due to its high variability and human subjectivity, there is an insistent need to develop an efficient method for automatic image segmentation and classification. This article develops an automatic segmentation and classification framework based on artificial intelligence (AI) on the ANA images. The Otsu thresholding method and watershed segmentation algorithm are adopted to segment IIF images of cells. Moreover, multiple texture features such as scale-invariant feature transform (SIFT), local binary pattern (LBP), cooccurrence among adjacent LBPs (CoALBP), and rotation invariant cooccurrence among adjacent LBPs (RIC-LBP) are utilized. Firstly, this article adopts traditional machine learning methods such as support vector machine (SVM), k-nearest neighbor algorithm (KNN), and random forest (RF) and then uses ensemble classifier (ECLF) combined with soft voting rules to merge these machine learning methods for classification. The deep learning method InceptionResNetV2 is also utilized to train on the classification of cell images. Eventually, the best accuracy of 0.9269 on the Changsha dataset and 0.9635 on the ICPR 2016 dataset for the traditional methods is obtained by a combination of SIFT and RIC-LBP with the ECLF classifier, and the best accuracy obtained by the InceptionResNetV2 is 0.9465 and 0.9836 separately, which outperforms other schemes.


Subject(s)
Antibodies, Antinuclear , Deep Learning , Humans , Artificial Intelligence , Algorithms , Machine Learning
4.
Technol Health Care ; 31(1): 165-179, 2023.
Article in English | MEDLINE | ID: mdl-35964217

ABSTRACT

BACKGROUND: Carotid atherosclerosis plaque rupture is an important cause of myocardial infarction and stroke. The effective segmentation of ultrasound images of carotid atherosclerotic plaques aids clinicians to accurately assess plaque stability. At present, this procedure relies mainly on the experience of the medical practitioner to manually segment the ultrasound image of the carotid atherosclerotic plaque. This method is also time-consuming. OBJECTIVE: This study intends to establish an automatic intelligent segmentation method of ultrasound images of carotid plaque. METHODS: The present study combined the U-Net and DenseNet networks, to automatically segment the ultrasound images of carotid atherosclerotic plaques. The same test set was selected and segmented using the traditional U-Net network and the ResUNet network. The prediction results of the three network models were compared using Dice (Dice similarity coefficient), and VOE (volumetric overlap error) coefficients. RESULTS: Compared with the existing U-Net network and ResUNet network, the Dense-UNet network exhibited an optimal effect on the automated segmentation of the ultrasound images. CONCLUSION: The Dense-UNet network could realize the automatic segmentation of atherosclerotic plaque ultrasound images, and it could assist medical practitioners in plaque evaluation.


Subject(s)
Carotid Artery Diseases , Plaque, Atherosclerotic , Stroke , Humans , Plaque, Atherosclerotic/diagnostic imaging , Carotid Arteries/diagnostic imaging , Carotid Artery Diseases/diagnostic imaging , Ultrasonography/methods , Image Processing, Computer-Assisted/methods
5.
Pharmaceutics ; 14(8)2022 Jul 25.
Article in English | MEDLINE | ID: mdl-35893797

ABSTRACT

Chemokines can induce chemotactic cell migration by interacting with G protein-coupled receptors to play a significant regulatory role in the development of cancer. CXC chemokine-12 (CXCL12) can specifically bind to CXC chemokine receptor 4 (CXCR4) and is closely associated with the progression of cancer via multiple signaling pathways. Over recent years, many CXCR4 antagonists have been tested in clinical trials; however, Plerixafor (AMD3100) is the only drug that has been approved for marketing thus far. In this review, we first summarize the mechanisms that mediate the physiological effects of the CXCL12/CXCR4 axis. Then, we describe the use of CXCL12/CXCR4 antagonists. Finally, we discuss the use of nano-based drug delivery systems that exert action on the CXCL12/CXCR4 biological axis.

6.
J Nanobiotechnology ; 19(1): 421, 2021 Dec 14.
Article in English | MEDLINE | ID: mdl-34906155

ABSTRACT

BACKGROUND: Cancer-associated fibroblasts (CAFs), as an important component of stroma, not only supply the "soils" to promote tumor invasion and metastasis, but also form a physical barrier to hinder the penetration of therapeutic agents. Based on this, the combinational strategy that action on both tumor cells and CAFs simultaneously would be a promising approach for improving the antitumor effect. RESULTS: In this study, the novel multifunctional liposomes (IRI-RGD/R9-sLip) were designed, which integrated the advantages including IRI and scFv co-loading, different targets, RGD mediated active targeting, R9 promoting cell efficient permeation and lysosomal escape. As expected, IRI-RGD/R9-sLip showed enhanced cytotoxicity in different cell models, effectively increased the accumulation in tumor sites, as well as exhibited deep permeation ability both in vitro and in vivo. Notably, IRI-RGD/R9-sLip not only exhibited superior in vivo anti-tumor effect in both CAFs-free and CAFs-abundant bearing mice models, but also presented excellent anti-metastasis efficiency in lung metastasis model. CONCLUSION: In a word, the novel combinational strategy by coaction on both "seeds" and "soils" of the tumor provides a new approach for cancer therapy, and the prepared liposomes could efficiently improve the antitumor effect with promising clinical application prospects.


Subject(s)
Cancer-Associated Fibroblasts/drug effects , Colorectal Neoplasms/metabolism , Drug Delivery Systems/methods , Irinotecan , Liposomes , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Coculture Techniques , Colorectal Neoplasms/pathology , Female , Irinotecan/chemistry , Irinotecan/pharmacokinetics , Irinotecan/pharmacology , Liposomes/chemistry , Liposomes/pharmacokinetics , Liposomes/pharmacology , Mice , Mice, Inbred BALB C , NIH 3T3 Cells , Single-Chain Antibodies/chemistry , Single-Chain Antibodies/pharmacokinetics
7.
J Cardiovasc Magn Reson ; 23(1): 120, 2021 10 25.
Article in English | MEDLINE | ID: mdl-34689798

ABSTRACT

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by increased left ventricular wall thickness, cardiomyocyte hypertrophy, and fibrosis. Adverse cardiac risk characterization has been performed using late gadolinium enhancement (LGE), native T1, and extracellular volume (ECV). Relaxation time constants are affected by background field inhomogeneity. T1ρ utilizes a spin-lock pulse to decrease the effect of unwanted relaxation. The objective of this study was to study T1ρ as compared to T1, ECV, and LGE in HCM patients. METHODS: HCM patients were recruited as part of the Novel Markers of Prognosis in Hypertrophic Cardiomyopathy study, and healthy controls were matched for comparison. In addition to cardiac functional imaging, subjects underwent T1 and T1ρ cardiovascular magnetic resonance imaging at short-axis positions at 1.5T. Subjects received gadolinium and underwent LGE imaging 15-20 min after injection covering the entire heart. Corresponding basal and mid short axis LGE slices were selected for comparison with T1 and T1ρ. Full-width half-maximum thresholding was used to determine the percent enhancement area in each LGE-positive slice by LGE, T1, and T1ρ. Two clinicians independently reviewed LGE images for presence or absence of enhancement. If in agreement, the image was labeled positive (LGE + +) or negative (LGE --); otherwise, the image was labeled equivocal (LGE + -). RESULTS: In 40 HCM patients and 10 controls, T1 percent enhancement area (Spearman's rho = 0.61, p < 1e-5) and T1ρ percent enhancement area (Spearman's rho = 0.48, p < 0.001e-3) correlated with LGE percent enhancement area. T1 and T1ρ percent enhancement areas were also correlated (Spearman's rho = 0.28, p = 0.047). For both T1 and T1ρ, HCM patients demonstrated significantly longer relaxation times compared to controls in each LGE category (p < 0.001 for all). HCM patients also showed significantly higher ECV compared to controls in each LGE category (p < 0.01 for all), and LGE -- slices had lower ECV than LGE + + (p = 0.01). CONCLUSIONS: Hyperenhancement areas as measured by T1ρ and LGE are moderately correlated. T1, T1ρ, and ECV were elevated in HCM patients compared to controls, irrespective of the presence of LGE. These findings warrant additional studies to investigate the prognostic utility of T1ρ imaging in the evaluation of HCM patients.


Subject(s)
Cardiomyopathy, Hypertrophic , Contrast Media , Cardiomyopathy, Hypertrophic/diagnostic imaging , Cardiomyopathy, Hypertrophic/pathology , Fibrosis , Gadolinium , Humans , Magnetic Resonance Imaging, Cine , Magnetic Resonance Spectroscopy , Myocardium/pathology , Predictive Value of Tests
8.
Biomaterials ; 276: 121003, 2021 09.
Article in English | MEDLINE | ID: mdl-34273686

ABSTRACT

Peripheral nerves have emerged as the important components in tumor microenvironment (TME), which could activate hepatic stellate cells (HSCs) by secreting substance P (SP), leading to hepatocellular carcinoma (HCC) invasion and metastasis. Herein, we proposed a novel anti-HCC concept of blocking "SP-HSCs-HCC" axis for omnidirectional inhibition of HCC development. To pursue this aim, the novel CAP/GA-sHA-DOX NPs were developed for targeted co-delivery of capsaicin (CAP) and doxorubicin (DOX) using glycyrrhetinic acid (GA) modified sulfated-HA (sHA) as nanocarriers. Among that, CAP could inhibit the activation of HSCs as an inhibitor of SP. Notably, to real mimic "SP-HSCs-HCC" axis for in vitro and in vivo evaluation, both "SP + LX-2+BEL-7402" co-cultured cell model and "SP + m-HSC + H22" co-implantation mice model were attempted for the first time. Furthermore, in vivo anti-HCC effects were performed in three different tumor-bearing models: subcutaneous implantation of H22 or "SP + m-HSC + H22", intravenous injection of H22 for lung metastasis, and orthotopic implantation of H22 for primary HCC. Our results showed that CAP/GA-sHA-DOX NPs could be efficiently taken up by tumor cells and activated HSCs (aHSCs) simultaneously, and effectively inhibit tumor drug-resistance and migration by blocking SP-induced HSCs activation. In addition, CAP/GA-sHA-DOX NPs exhibited low ECM deposition, less tumor angiogenesis, and superior in vivo anti-HCC effects. The anti-HCC mechanisms revealed that CAP/GA-sHA-DOX NPs could down-regulate the expression level of Vimentin and P-gp, reverse epithelial-mesenchymal transition (EMT) of tumor cells. In brief, the nano-sized combination therapy based on GA-sHA-DOX polymers could effectively inhibit drug-resistance and metastasis of HCC by blocking "SP-HSCs-HCC" axis, which provides a promising approach for cancer therapy.


Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Hepatocellular , Drug Resistance, Neoplasm , Liver Neoplasms , Animals , Carcinoma, Hepatocellular/drug therapy , Cell Line, Tumor , Hepatic Stellate Cells , Liver Neoplasms/drug therapy , Mice , Substance P , Tumor Microenvironment
9.
Nanoscale ; 13(23): 10509-10525, 2021 Jun 17.
Article in English | MEDLINE | ID: mdl-34096957

ABSTRACT

Cancer-associated fibroblasts (CAFs) play a crucial role in facilitating tumor invasion and metastasis, which act as the "soil" in the tumor microenvironment (TME). Accordingly, it would be a promising strategy to enhance the antitumor effect by killing both tumor cells and CAFs simultaneously. Herein, novel TME acid-responsive liposomes for co-delivery of IRI and 398 (IRI&398-s-LPs) were developed, in which the rapid release of both drugs could be triggered under acidic conditions. Notably, a CT-26/3T3 cell co-culture system was used to mimic the real TME both in vitro and in vivo. Cellular immunofluorescence revealed that IRI&398-s-LPs could efficiently decrease the activation of CAFs. In vitro cytotoxicity evaluation demonstrated that IRI&398-s-LPs exhibited higher cytotoxicity than the other liposomal formulations in the CT-26 and CT-26/3T3 cell co-culture system. In vivo NIRF imaging showed that the IRI&398-s-LPs could increase drug accumulation in the tumor sites. Furthermore, IRI&398-s-LPs not only presented superior in vivo anti-tumor activity in CT-26 bearing BALB/c mice, but also enhanced the effect in CT-26/3T3 cell bearing mice with decreased collagen and CAF biomarker expression. Furthermore, IRI&398-s-LPs also presented superior anti-metastatic efficiency in a lung metastasis model. These results indicated that this combinational strategy for eliminating both tumor cells and CAFs provides a new approach for cancer therapy, and the prepared TME-responsive liposomes for co-delivery of drugs hold promising clinical application prospects.


Subject(s)
Cancer-Associated Fibroblasts , Colorectal Neoplasms , Animals , Cell Line, Tumor , Colorectal Neoplasms/drug therapy , Liposomes , Mice , Mice, Inbred BALB C , Tumor Microenvironment
10.
Int J Nanomedicine ; 16: 4001-4016, 2021.
Article in English | MEDLINE | ID: mdl-34135585

ABSTRACT

BACKGROUND: Tumor angiogenesis has been proven to potentiate tumor growth and metastasis; therefore, the strategies targeting tumor-related angiogenesis have great potentials in antitumor therapy. METHODS: Here, the GA&Gal dual-ligand-modified liposomes co-loaded with curcumin and combretastatin A-4 phosphate (CUCA/GA&Gal-Lip) were prepared and characterized. A novel "BEL-7402+HUVEC" co-cultured cell model was established to mimic tumor microenvironment. The cytotoxicity and migration assays were performed against the novel co-cultured model. Angiogenesis ability was evaluated by tube formation test, and in vivo metastatic ability was evaluated by lung metastasis test. RESULTS: The result demonstrated that dual-ligand-modified liposomes showed greater inhibition of tumor angiogenesis and metastasis in comparison with other combined groups. Significantly, the mechanism analysis revealed that curcumin and combretastatin A-4 phosphate could inhibit tumor angiogenesis and metastasis via down-regulation of VEGF and VEGFR2 expression, respectively, and that GA&Gal-Lip could improve antitumor effect by GA/Gal-mediated active-targeting delivery. CONCLUSION: CUCA/GA&Gal-Lip hold great potentials in hepatoma-targeting delivery of antitumor drugs and can achieve anti-angiogenic and anti-metastatic effects by simultaneously blocking VEGF/VEGFR2 signal pathway, therefore exhibiting superior anti-hepatoma efficacy.


Subject(s)
Angiogenesis Inhibitors/administration & dosage , Antineoplastic Agents, Phytogenic/administration & dosage , Liposomes/pharmacology , Neovascularization, Pathologic/drug therapy , Angiogenesis Inhibitors/pharmacology , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Curcumin/administration & dosage , Curcumin/pharmacokinetics , Drug Liberation , Gene Expression Regulation, Neoplastic/drug effects , Human Umbilical Vein Endothelial Cells , Humans , Ligands , Liposomes/administration & dosage , Liposomes/chemistry , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/secondary , Mice, Inbred BALB C , Stilbenes/administration & dosage , Stilbenes/pharmacology , Xenograft Model Antitumor Assays
11.
Biomolecules ; 12(1)2021 12 30.
Article in English | MEDLINE | ID: mdl-35053199

ABSTRACT

Bortezomib (BTZ) is the first proteasome inhibitor approved by the Food and Drug Administration. It can bind to the amino acid residues of the 26S proteasome, thereby causing the death of tumor cells. BTZ plays an irreplaceable role in the treatment of mantle cell lymphoma and multiple myeloma. Moreover, its use in the treatment of other hematological cancers and solid tumors has been investigated in numerous clinical trials and preclinical studies. Nevertheless, the applications of BTZ are limited due to its insufficient specificity, poor permeability, and low bioavailability. Therefore, in recent years, different BTZ-based drug delivery systems have been evaluated. In this review, we firstly discussed the functions of proteasome inhibitors and their mechanisms of action. Secondly, the properties of BTZ, as well as recent advances in both clinical and preclinical research, were reviewed. Finally, progress in research regarding BTZ-based nanoformulations was summarized.


Subject(s)
Antineoplastic Agents , Multiple Myeloma , Adult , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Bortezomib/pharmacology , Cell Line, Tumor , Drug Delivery Systems , Humans , Multiple Myeloma/drug therapy , Proteasome Inhibitors/pharmacology
12.
Colloids Surf B Biointerfaces ; 196: 111303, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32798988

ABSTRACT

Nano-based drug delivery systems have been widely applied in cancer therapy, among that, particle sizes may affect the delivery efficiency of nanocarriers. The purpose of this study was to evaluate the potential impacts of particle size on tumor therapy, in consideration of this, lipid/glycocholic acid mixed micelles (LGs) were designed as the model nanocarriers. Doxorubicin (DOX) loaded LGs with two different particle sizes at around 10 nm and 100 nm, respectively, were successfully prepared by controlling the ratio of EPC to GAH. In vitro release study showed that the release behaviors of DOX in mixed micelles with two different particle sizes was basically consistent and showed sustained release. DOX-LGs at 10 nm exhibited higher cellular uptake capacity, compared with DOX-LGs at 100 nm. Besides, in vivo NIFR imaging also demonstrated that DOX-LGs at 10 nm had more accumulation in tumor site. Furthermore, DOX-LGs at 10 nm presented both higher in vitro cytotoxicity and superior in vivo antitumor activity than that of 100 nm. In vivo safety evaluations showed that the mixed micelles had lower toxicities than free DOX solution formulations. These results indicated that the nanoparticles with smaller particle size could improve the profiles in cellular uptake, tumor accumulation as well as anti-tumor efficacy, which would provide a theoretical principle for the design of nanoparticles.


Subject(s)
Micelles , Neoplasms , Cell Line, Tumor , Doxorubicin/pharmacology , Drug Carriers , Humans , Neoplasms/drug therapy , Particle Size
13.
Int J Cardiovasc Imaging ; 36(11): 2139-2144, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32767023

ABSTRACT

Use of echocardiography to evaluate the characteristics of right heart and pulmonary artery of Tibetans with hepatic hydatidosis living in a high plateau area. We recruited 222 Tibetan adults diagnosed with hydatidosis from June 2016 to June 2017 in Shiqu and Seda areas of Tibet; 40 healthy control from the same area, denoted as the high plateau group. We also include 755 Healthy adults of Han nationality living in the plain from the EMINCA study as the low altitude group. Compared to high plateau group, hydatidosis individuals showed decreased RVADed, RVTDed, increased E(T)/A(T) and reduced RVFAC and TAPSE (p < 0.05). The 2 groups did not differ in the incidence rate of tricuspid regurgitation (TR) and pulmonary regurgitation (PR) (63.9% vs. 55.0%, p = 0.281 and 15.3% vs. 5.0%, p = 0.135, respectively) or incidence of pulmonary hypertension (PH) (13.9% vs. 20.5%, p = 0.167). PH risk did not differ between hydatidosis individuals and high plateau controls (OR 0.559, 95% CI 0.243-1.287). The RVADed and TAPSE were higher and E(T)/A(T) was lower for high plateau group than low altitude group (p < 0.05). The decreased right ventricular size and reduced diastolic and systolic function were found in Tibetans with hydatidosis. Hepatic hydatidosis had no significant effect on the incidence of pulmonary hypertension in Tibetans. Healthy Tibetans showed increased right ventricular size, decreased diastolic function, and increased systolic function compared to the Han counterparts.


Subject(s)
Acclimatization , Altitude , Echinococcosis, Hepatic/diagnosis , Echocardiography, Doppler, Color , Hypertension, Pulmonary/diagnosis , Adolescent , Adult , Aged , Arterial Pressure , Asian People , Cardiac Catheterization , Case-Control Studies , Echinococcosis, Hepatic/ethnology , Echinococcosis, Hepatic/physiopathology , Female , Humans , Hypertension, Pulmonary/ethnology , Hypertension, Pulmonary/physiopathology , Incidence , Male , Middle Aged , Predictive Value of Tests , Prognosis , Race Factors , Tibet/epidemiology , Ventricular Function, Right , Ventricular Remodeling , Young Adult
14.
J Drug Target ; 28(7-8): 714-726, 2020.
Article in English | MEDLINE | ID: mdl-32183540

ABSTRACT

Tumour microenvironment provides the 'soil' for tumour growth. Besides tumour cells, there are also numbers of stromal cells, extracellular matrix and other components in the tumour microenvironment. In the past years, kinds of ligands and markers specifically high-expressed on the surface of the tumour stromal cells have been explored, which can be used as the therapeutic targets for cancer treatment. Recently, the antitumor drugs by targeting stromal cells, including small-molecular inhibitor and large-molecular monoclonal antibody, have been widely discovered and applied in clinic attributed to their specific targeting ability. Moreover, the targeted drug delivery system also paid more and more attentions due to their desired profiles in increased accumulation at tumour sites, enhanced antitumor ability and less toxicity and side effects. Therefore, it is of great significance to find and construct drug delivery systems targeting tumour stromal cells. In this review, we discussed the widely recognised therapeutic targets on tumour stromal cells, besides, the current status on the targeting drugs as well as the drug delivery systems were also highlighted.


Subject(s)
Antineoplastic Agents/therapeutic use , Neoplasms/therapy , Stromal Cells/physiology , Tumor Microenvironment , Animals , Antineoplastic Agents/administration & dosage , Drug Delivery Systems , Humans
15.
Sci Total Environ ; 708: 134824, 2020 Mar 15.
Article in English | MEDLINE | ID: mdl-31796273

ABSTRACT

Desertification and eutrophication are two global environmental problems human beings face. Inoculating cyanobacteria to form biocrusts is considered an effective technology to inhibit desertification. The main limitation of biocrust formation is the lack of propagules and nutrients in deserts. A possible low cost source of propagules and nutrients is eutrophic water containing aquatic cyanobacteria (AC), nitrogen and phosphorus. In this study, we fabricated a network-structured nanocomposite (designated as MC) using a metal-organic framework (MOF) and carboxymethyl cellulose (CMC). MC, with a large specific surface area and numerous surface groups, had a high retention capacity for water and nutrients and good biosafety. The combination of AC-containing water (ACW) and MC could provide a suitable microenvironment in the soil, promote the growth of desert cyanobacteria (DC), formation of biocrusts and inhibition of desertification. This study provides a novel approach to simultaneously relieve desertification and eutrophication.


Subject(s)
Cyanobacteria , Nanocomposites , Ecosystem , Eutrophication , Nitrogen , Soil
17.
Int J Cardiovasc Imaging ; 33(11): 1663-1671, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28500378

ABSTRACT

To assess the elastic mechanical properties of atherosclerotic plaque with different morphological properties by intravascular ultrasound elastography (IVUSE). 30 purebred New Zealand rabbits were fed a high-cholesterol diet; the abdominal aorta endothelium was balloon-injured after 2 weeks; at week 12, 2 plaques with moderate echo from each rabbit were chosen for in situ imaging, and 2 consecutive frames near the end-diastole images in situ were used to construct an IVUS elastogram. Shear strain (SS) and area strain (AS) were greater for eccentric than centripetal plaque (SS: 2.65(2.45)% vs. 1.79 ± 0.97%, p < 0.05; AS: 4.81(4.99)% vs. 3.23 ± 1.75%, p < 0.05) but were lower with low than high plaque burden (SS: 2.14 ± 0.37% vs. 3.40 ± 0.34%, p < 0.05; AS: 3.88 ± 0.60% vs. 5.81 ± 0.54%, p < 0.05). SS and AS were significantly greater for plaque with negative than no remodeling (SS: 3.98 ± 1.53% vs. 1.82(1.40)%, p < 0.017; AS: 6.94 ± 2.24% vs. 2.59(2.87)%, p < 0.017) and were found correlated with eccentric index and plaque burden (R2 = 0.365 and R2 = 0.359, both p < 0.05). Plaques associated with eccentricity, high plaque burden and negative remodeling showed greater strain than those with centripetalism, low plaque burden and positive remodeling. Eccentric index and plaque burden may be useful to predict the elastic stability of plaque.


Subject(s)
Aorta, Abdominal/diagnostic imaging , Aortic Diseases/diagnostic imaging , Elasticity Imaging Techniques/methods , Plaque, Atherosclerotic , Ultrasonography, Interventional , Vascular System Injuries/diagnostic imaging , Animals , Aorta, Abdominal/injuries , Aorta, Abdominal/pathology , Aorta, Abdominal/physiopathology , Aortic Diseases/etiology , Aortic Diseases/pathology , Aortic Diseases/physiopathology , Biomechanical Phenomena , Cholesterol, Dietary , Diet, High-Fat , Disease Models, Animal , Elasticity , Male , Predictive Value of Tests , Rabbits , Vascular Remodeling , Vascular System Injuries/etiology , Vascular System Injuries/pathology , Vascular System Injuries/physiopathology
18.
Ultrasound Med Biol ; 42(8): 1730-40, 2016 08.
Article in English | MEDLINE | ID: mdl-27126237

ABSTRACT

The aim of this study was to assess left ventricular (LV) energy loss (EL) using vector flow mapping in patients with prediabetes (pre-DM) and type 2 diabetes mellitus (DM). Thirty pre-DM patients, 51 DM patients, and 38 controls were studied by transthoracic echocardiography. EL-total, EL-base, EL-mid and EL-apex climaxed at different phases. Compared with controls, pre-DM and DM patients showed increased EL-total during slow ejection, isovolumic relaxation, rapid filling and slow filling (p < 0.05). Similarly, EL-base, EL-mid and EL-apex increased during certain phases. Stepwise multiple regression analysis revealed that the early transmitral valve blood flow velocity E, the late transmitral valve blood flow velocity A, the ratio of E/A, LV peak torsion, diastolic untwisting velocity, vortex circulation and area were independently associated with EL during different phases (all p < 0.05). Our study suggests that LV EL is increased during diastole and certain phases of systole in DM patients compared with controls. The changes in LV vortex and deformation mechanics were correlated with EL.


Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Prediabetic State/physiopathology , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/physiopathology , Blood Flow Velocity/physiology , Cross-Sectional Studies , Female , Heart Ventricles/diagnostic imaging , Heart Ventricles/physiopathology , Humans , Male , Middle Aged , Reproducibility of Results
19.
Atherosclerosis ; 248: 27-35, 2016 May.
Article in English | MEDLINE | ID: mdl-26978584

ABSTRACT

OBJECTIVES: The present study aimed to investigate the effect of potent rosuvastatin therapy on plaque mechanical stabilization as seen on IVUSE. METHODS: 14 purebred New Zealand rabbits were fed a high-cholesterol diet; the abdominal aorta endothelium was balloon-injured after 2 weeks; at week 13, 7 rabbits received rosuvastatin (1.5 mg/kg/day), and the other 7 received an equal volume of saline. IVUS images of abdominal aortas were acquired, and 2 consecutive frames near the end-diastole images in situ were used to construct an IVUS elastogram. RESULTS: Control rabbits showed a significant increase in shear strain (SS) and area strain (AS) in total plaques. The rosuvastatin group showed no change in SS and AS, but serum TG and LDL-C levels were reduced, with less lipid deposition, macrophage infiltration, production of proinflammatory cytokines and apoptosis in plaques. The changes in SS and AS from baseline between groups significantly differed (SS: 1.15 (1.96) % vs. -0.99 ± 2.83%, p = 0.013; AS: 1.25 (2.29) % vs. -1.67 ± 5.05%, p = 0.022). At follow-up, for controls, strain values were increased in the shoulder of eccentric plaques (SS: 2.66 ± 1.31% vs. 4.86 ± 1.93%, p = 0.016; AS: 4.45 ± 2.33% vs. 7.91 ± 2.74%, p = 0.009) but not the plaque body. Changes in SS and AS in the plaque shoulder differed between the control and rosuvastatin groups (SS: 2.20 ± 2.17% vs. -0.87 ± 3.31%, p = 0.028; AS: 2.10 (4.61) % vs. -2.75 ± 5.97%, p = 0.009). CONCLUSION: Rosuvastatin therapy in rabbits with atherosclerotic plaques led to less vulnerable plaque features. IVUSE is a very sensitive technique for detecting pharmacologically-induced mechanical changes in rabbit atherosclerotic plaques.


Subject(s)
Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/drug therapy , Rosuvastatin Calcium/therapeutic use , Ultrasonography, Interventional , Animals , Anticholesteremic Agents/therapeutic use , Aorta, Abdominal , Atherosclerosis , Disease Models, Animal , Elasticity Imaging Techniques , Image Processing, Computer-Assisted , Inflammation , Male , Rabbits , Rupture , Shear Strength , Stress, Mechanical
20.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 28(6): 1170-4, 2011 Dec.
Article in Chinese | MEDLINE | ID: mdl-22295708

ABSTRACT

The present study was to investigate in vitro the rat cardiomyocyte injury with targeting of home-made perfluorocarbon lipid particles with avidin-biotin interaction. Neonatal rat cardiomyocytes were cultured in vitro and divided into two groups: TNF-alpha activated group and non-activated group. Those in the TNF-alpha activated group were exposed to 200 ng/ml TNF-alpha solution for 6 hours and then cardiomyocytes in both groups were pretargeted with biotinylated ICAM-1 monoclonal antibodies, and were exposed to streptavidin, and then to homemade green fluorescently-labeled biotinylated perfluorocarbon lipid particles. Cardiomyocytes nucleus stained with Hoechst. The results were detected with fluorescence microscope. As a result, in TNF-alpha activated group, around blue fluorescent cardiomyocytes nucleus, a great amount of green fluorescent particles were found, while there were few green fluorescent particles in non-TNF activated group. It has been shown that ICAM-1 is expressed in the surface of cardiomyocytes when they are stimulated by TNF-alpha. Perfluorocarbon lipid particles associated with ICAM-1 monoclonal antibodies can be targeted to injured cardiomyocytes by avidin-biotin interaction.


Subject(s)
Fluorocarbons/metabolism , Myocytes, Cardiac/pathology , Ultrasonography , Animals , Animals, Newborn , Antibodies, Monoclonal/metabolism , Cells, Cultured , Contrast Media , Female , Fluorocarbons/immunology , Intercellular Adhesion Molecule-1/metabolism , Lipids/chemistry , Male , Microspheres , Myocytes, Cardiac/metabolism , Rats , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/pharmacology
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