Advantage in Bright-blood and Black-blood Magnetic Resonance Imaging with High-resolution for Analysis of Carotid Atherosclerotic Plaques

Background:

About 50% of the cerebral ischemia events are induced by intracranial and extracranial atherosclerosis. This study aimed to evaluate the feasibility and accuracy for displaying atherosclerotic plaques in carotid arteries and analyzing their ingredients by using high-resolution new magnetic resonance imaging (MRI) techniques.

Methods:

Totally, 49 patients suspected of extracranial carotid artery stenosis were subjected to cranial MRI scan and magnetic resonance angiography (MRA) examination on carotid arteries, and high-resolution bright-blood and black-blood MRI analysis was carried out within 1 week. Digital subtraction angiography (DSA) examination was carried out for 16 patients within 1 month.

Results:

Totally, 103 plaques were detected in the 49 patients, which were characterized by localized or diffusive thickening of the vessel wall, with the intrusion of crescent-shaped abnormal signal into lumens. Fibrous cap was displayed as isointensity in T1-weighted image (T1WI) and hyperintensities in proton density weighted image (PDWI) and T2-weighted image (T2WI), lipid core was displayed as isointensity or slight hyperintensities in T1WI, isointensity, hyperintensities or hypointensity in PDWI, and hypointensity in T2WI. Calcification in plaques was detected in 11 patients. Eight patients were detected with irregular plaque surface or ulcerative plaques, which were characterized by irregular intravascular space surface in the black-blood sequences, black hypointensity band was not detected in three-dimensional time-of-flight, or the hypointensity band was not continuous, and intrusion of hyperintensities into plaques can be detected. Bright-blood and black-blood techniques were highly correlated with the diagnosis of contrast-enhanced MRA in angiostenosis degree, Rs = 0.97, P < 0.001. In comparison to DSA, the sensitivity, specificity, and accuracy of MRI diagnosis of stenosis for ≥50% were 88.9%, 100%, and 97.9%, respectively.

Conclusions:

High-resolution bright-blood and black-blood sequential MRI analysis can accurately analyze ingredients in atherosclerotic plaques. Determined by DSA, MRI diagnosis of stenosis can correctly evaluate the serious degree of arteriostenosis.     

Autophagy in 5-Fluorouracil Therapy in Gastrointestinal Cancer: Trends and Challenges

Objective:

5-Fluorouracil (5-FU)-based combination therapies are standard treatments for gastrointestinal cancer, where the modulation of autophagy is becoming increasingly important in offering effective treatment for patients in clinical practice. This review focuses on the role of autophagy in 5-FU-induced tumor suppression and cancer therapy in the digestive system.

Data Sources:

All articles published in English from 1996 to date those assess the synergistic effect of autophagy and 5-FU in gastrointestinal cancer therapy were identified through a systematic online search by use of PubMed. The search terms were “autophagy” and “5-FU” and (“colorectal cancer” or “hepatocellular carcinoma” or “pancreatic adenocarcinoma” or “esophageal cancer” or “gallbladder carcinoma” or “gastric cancer”).

Study Selection:

Critical reviews on relevant aspects and original articles reporting in vitro and/or in vivo results regarding the efficiency of autophagy and 5-FU in gastrointestinal cancer therapy were reviewed, analyzed, and summarized. The exclusion criteria for the articles were as follows: (1) new materials (e.g., nanomaterial)-induced autophagy; (2) clinical and experimental studies on diagnostic and/or prognostic biomarkers in digestive system cancers; and (3) immunogenic cell death for anticancer chemotherapy.

Results:

Most cell and animal experiments showed inhibition of autophagy by either pharmacological approaches or via genetic silencing of autophagy regulatory gene, resulting in a promotion of 5-FU-induced cancer cells death. Meanwhile, autophagy also plays a pro-death role and may mediate cell death in certain cancer cells where apoptosis is defective or difficult to induce. The dual role of autophagy complicates the use of autophagy inhibitor or inducer in cancer chemotherapy and generates inconsistency to an extent in clinic trials.

Conclusion:

Autophagy might be a therapeutic target that sensitizes the 5-FU treatment in gastrointestinal cancer.     

Alterations of Thymic Epithelial Cells in Lipopolysaccharide-induced Neonatal Thymus Involution

Background:

Vascular endothelial growth factor (VEGF) in the thymus was mainly produced by the thymic epithelial cells (TECs), the predominant component of the thymic microenvironment. The progression of TECs and the roles of VEGF in the neonatal thymus during sepsis have not been reported. This study aimed to explore the alterations of TECs and VEGF level in the neonatal thymus involution and to explore the possible mechanisms at the cellular level.

Methods:

By establishing a model of clinical sepsis, the changes of TECs were measured by hematoxylin-eosin staining, confocal microscopy, and flow cytometry. Moreover, the levels of VEGF in serum and thymus were assessed based on enzyme-linked immunosorbent assay and Western blotting.

Results:

The number of thymocytes and TECs was significantly decreased 24 h after lipopolysaccharide (LPS) challenge, (2.40 ± 0.46)×10⁷ vs. (3.93 ± 0.66)×10⁷ and (1.16 ± 0.14)×10⁵ vs. (2.20 ± 0.19)×10⁵, P < 0.05, respectively. Cortical TECs and medullary TECs in the LPS-treated mice were decreased 1.5-fold and 3.9-fold, P < 0.05, respectively, lower than those in the controls. The number of thymic epithelial progenitors was also decreased. VEGF expression in TECs was down-regulated in a time-dependent manner.

Conclusion:

VEGF in thymic cells subsets might contribute to the development of TECs in neonatal sepsis.     

Serum level of copper in patients with coronary artery disease

Background:

Atherosclerotic disease is the most important cause of mortality in the world. Oxidation is an important pathway in the pathogenesis of coronary artery disease (CAD) through oxidation of low-density lipoprotein (LDL) and free radical formation. Copper (Cu) is an essential micronutrient for enzymes that catalyse LDL oxidation reactions. Therefore, an evaluation of Cu in the atherosclerotic disease is important.

Materials and Methods:

In this study, 334 subjects without recent cardiac event and history of collagen vascular or infectious disease were investigated. All patients divided into four groups to evaluate severity of CAD according to Syntax scoring system. All groups were matched in cardiovascular risk factors.

Results:

The serum level of Cu was significantly higher in total atherosclerotic groups than normal group (P value = 0.001) and significantly increased with severity of atherosclerosis.

Conclusion:

The finding indicated that the serum level of Cu is higher in atherosclerotic patients and it increases with severity of atherosclerosis. Therefore, it may be possible that the basic relationship exist between serum Cu level and atherosclerosis and an association between Cu level and severity of atherosclerosis.     

Calcium Phosphate Scaffolds Combined with Bone Morphogenetic Proteins or Mesenchymal Stem Cells in Bone Tissue Engineering

Objective:

The purpose of this study was to review the current status of calcium phosphate (CaP) scaffolds combined with bone morphogenetic proteins (BMPs) or mesenchymal stem cells (MSCs) in the field of bone tissue engineering (BTE).

Date Sources:

Data cited in this review were obtained primarily from PubMed and Medline in publications from 1979 to 2014, with highly regarded older publications also included. The terms BTE, CaP, BMPs, and MSC were used for the literature search.

Study Selection:

Reviews focused on relevant aspects and original articles reporting in vitro and/or in vivo results concerning the efficiency of CaP/BMPs or CaP/MSCs composites were retrieved, reviewed, analyzed, and summarized.

Results:

An ideal BTE product contains three elements: Scaffold, growth factors, and stem cells. CaP-based scaffolds are popular because of their outstanding biocompatibility, bioactivity, and osteoconductivity. However, they lack stiffness and osteoinductivity. To solve this problem, composite scaffolds of CaP with BMPs have been developed. New bone formation by CaP/BMP composites can reach levels similar to those of autografts. CaP scaffolds are compatible with MSCs and CaP/MSC composites exhibit excellent osteogenesis and stiffness. In addition, a CaP/MSC/BMP scaffold can repair bone defects more effectively than an autograft.

Conclusions:

Novel BTE products possess remarkable osteoconduction and osteoinduction capacities, and exhibit balanced degradation with osteogenesis. Further work should yield safe, viable, and efficient materials for the repair of bone lesions.     

Wall Imaging for Unilateral Intracranial Vertebral Artery Hypoplasia with Three-dimensional High-isotropic Resolution Magnetic Resonance Images

Background:

There are few studies for evaluating wall characteristics of intracranial vertebral artery hypoplasia (VAH). The aim of this study was to determine wall characteristics of VAH with three-dimensional volumetric isotropic turbo spin echo acquisition (3D VISTA) images and differentiate between acquired atherosclerotic stenosis and VAH.

Methods:

Thirty patients with suspicious VAH by luminograms were retrospectively enrolled between January 2014 and February 2015. The patients were classified as “acquired atherosclerotic stenosis” or “VAH” based on 3D VISTA images. The wall characteristics of VAH were assessed to determine the presence of atherosclerotic lesions, and the patients were classified into two subgroups (VAH with atherosclerosis and VAH with normal wall). Wall characteristics of basilar arteries and vertebral arteries were also assessed. The clinical and wall characteristics were compared between the two groups.

Results:

Five of 30 patients with suspicious VAH were finally diagnosed as acquired atherosclerotic stenosis by 3D VISTA images. 25 patients were finally diagnosed as VAH including 16 (64.00%) patients with atherosclerosis and 9 (36.00%) patients with normal wall. In the 16 patients with atherosclerosis, plaque was found in 9 patients, slight wall thickening in 6 patients, and thrombus and wall thickening in 1 patient. Compared with VAH patients with normal wall, VAH patients with atherosclerosis showed atherosclerotic basilar arteries and dominant vertebral arteries more frequently (P = 0.000).

Conclusions:

Three-dimensional VISTA images enable differentiation between the acquired atherosclerotic stenosis and VAH. VAH was also prone to atherosclerotic processes.     

Diagnostic Significance of Intraoperative Ultrasound Contrast in Evaluating the Resection Degree of Brain Glioma By Transmission Electron Microscopic Examination

Background:Contrast-enhanced ultrasound is a dynamic and continuous modality providing real-time view of vascularization and flow distribution patterns of different organs and tumors.In order to evalua...     

Inactivated Sendai Virus Induces ROS-dependent Apoptosis and Autophagy in Human Prostate Cancer Cells

Objective

The current study aims to investigate the effect of Hemagglutinating virus of Japan envelope (HVJ-E) on induction of apoptosis and autophagy in human prostate cancer PC3 cells, and the underlying mechanisms.

Expression of Potassium Channels in Uterine Smooth Muscle Cells from Patients with Adenomyosis

Background:

Adenomyosis (AM) has impaired contraction. This study aimed to explore the expression of potassium channels related to contraction in myometrial smooth muscle cells (MSMCs) of AM.

Methods:

Uterine tissue samples from 22 patients (cases) with histologically confirmed AM and 12 (controls) with cervical intraepithelial neoplasia were collected for both immunohistochemistry and real-time polymerase chain reaction to detect the expression of large conductance calcium- and voltage-sensitive K⁺ channel (BKCa)-α/β subunits, voltage-gated potassium channel (Kv) 4.2, and Kv4.3. Student''s t-test was used to compare the expression.

Results:

The BKCa-α/β subunits, Kv4.2, and Kv4.3 were located in smooth muscle cells, glandular epithelium, and stromal cells. However, BKCa-β subunit expression in endometrial glands of the controls was weak, and Kv4.3 was almost undetectable in the controls. The expression of BKCa-α messenger RNA (mRNA) (0.62 ± 0.19-fold decrease, P < 0.05) and Kv4.3 mRNA (0.67 ± 0.20-fold decrease, P < 0.05) decreased significantly in the MSMCs of the control group compared with the AM group. However, there were no significant differences in BKCa-β subunit mRNA or Kv4.2 mRNA.

Conclusions:

The BKCa-α mRNA and the Kv4.3 mRNA are expressed significantly higher in AM than those in the control group, that might cause the abnormal uterus smooth muscle contractility, change the microcirculation of uterus to accumulate the inflammatory factors, impair the endometrium further, and aggravate the pain.     

Current and Future Clinical Applications of Zinc Transporter-8 in Type 1 Diabetes Mellitus

Objective:

To evaluate the utility of zinc transporter-8 (ZnT8) in the improvement of type 1 diabetes mellitus (T1DM) diagnosis and prediction, and to explore whether ZnT8 is a potential therapeutic target in T1DM.

Data Sources:

A search was conducted within the medical database PubMed for relevant articles published from 2001 to 2015. The search terms are as follows: “ZnT8,” “type 1 diabetes,” “latent autoimmune diabetes in adults,” “type 2 diabetes,” “islet autoantibodies,” “zinc supplement,” “T cells,” “β cell,” “immune therapy.” We also searched the reference lists of selected articles.

Study Selection:

English-language original articles and critical reviews concerning ZnT8 and the clinical applications of islet autoantibodies in diabetes were reviewed.

Results:

The basic function of ZnT8 is maintaining intracellular zinc homeostasis, which modulates the process of insulin biosynthesis, storage, and secretion. Autoantibodies against ZnT8 (ZnT8A) and ZnT8-specific T cells are the reliable biomarkers for the identification, stratification, and characterization of T1DM. Additionally, the results from the animal models and clinical trials have shown that ZnT8 is a diabetogenic antigen, suggesting the possibility of ZnT8-specific immunotherapy as an alternative for T1DM therapy.

Conclusions:

ZnT8 is a novel islet autoantigen with a widely potential for clinical applications in T1DM. However, before the large-scale clinical applications, there are still many problems to be solved.     

High-resolution Magnetic Resonance Imaging of Moyamoya Disease

Objective:

To introduce the imaging characteristics of moyamoya disease (MMD) using high-resolution magnetic resonance imaging (HR-MRI) and to discuss the role of HR-MRI in differentiating MMD from other intracranial artery diseases, especially intracranial atherosclerotic disease (ICAD).

Data Sources:

This review was based on the data in articles published between 2005 and 2015, which were obtained from PubMed. The keywords included HR-MRI, MMD, ICAD, and intracranial artery diseases.

Study Selection:

Articles related to HR-MRI for MMD or other intracranial artery diseases were selected for review.

Results:

There are differences between the characteristic patterns of HR-MRI in MMD and ICAD. MMD is associated with inward remodeling, smaller outer diameters, concentric occlusive lesions and homogeneous signal intensity, while ICAD is more likely to be associated with outward remodeling, normal outer diameters, eccentric occlusive lesions, and heterogeneous signal intensity. Other intracranial artery diseases, such as dissection and vasculitis, also have distinctive characteristics in HR-MRI. HR-MRI may become a useful tool for the differential diagnosis of MMD in the future.

Conclusions:

HR-MRI of MMD provides a more in-depth understanding of MMD, and it is helpful in evaluating pathological changes in the vessel wall and in differentiating MMD from other intracranial artery steno-occlusive diseases, particularly ICAD.     

Plaques of Nonstenotic Basilar Arteries with Isolated Pontine Infarction on Three-dimensional High Isotropic Resolution Magnetic Resonance Imaging

Background:

There are few studies for evaluating plaque characteristics of nonstenotic basilar arteries (BA). Our aim was to determine entire BA plaques with a three-dimensional volumetric isotropic turbo spin-echo acquisition (VISTA) and investigate the differences between the patients with and without isolated pontine infarction (IPI).

Methods:

Twenty-four consecutive symptomatic patients with nonstenotic BA on time of flight magnetic resonance angiography (TOF MRA) were enrolled from China-Japan Friendship Hospital between January 2014 and December 2014. BA was classified as “normal” or “irregular” based on TOF MRA, and “normal wall”, “slight wall-thickening”, and “plaque” based on three-dimensional VISTA images. Outcomes from MRA and VISTA were compared. Patients were categorized as IPI and non-IPI groups based on the diffusion-weighted imaging. Clinical and plaque characteristics were compared between the two groups.

Results:

A total of 1024 image slices including 311 (30.37%) plaque slices, 427 (41.70%) slight wall-thickening slices, and 286 (27.93%) normal wall slices for the entire BA from 23 patients were finally included for analysis. VISTA images detected plaques in all the 9 (100%) irregular MRA patients and 7 of 14 (50%) normal MRA patients. IPI was found in 11 (47.83%) patients. Compared to non-IPI group, the IPI group had a higher percentage of plaque slices (P = 0.001) and lower percentage of normal wall slices (P = 0.014) than non-IPI group.

Conclusions:

Three-dimensional VISTA images enable detection of BA plaques not visualized by MRA. BA plaques could be found in both the IPI and non-IPI group. However, IPI group showed plaques more extensively in BA than the non-IPI group.     

Na+/Ca2+ Exchanger 3 is Downregulated in the Hippocampus and Cerebrocortex of Rats with Hyperthermia-induced Convulsion

Background:

Na⁺/Ca²⁺ exchanger (NCX) plays a crucial role in pentylenetetrazol-induced convulsion. However, it is unclear whether NCX is critically involved in hyperthermia-induced convulsion. In this study, we examined the potential changes in NCX3 in the hippocampus and cerebrocortex of rats with hyperthermia-induced convulsion.

Methods:

Twenty-one Sprague Dawley rats were randomly assigned to control group, convulsion-prone group and convulsion-resistant group (n = 7 in each group). Whole-cell patch-clamp method was used to record NCX currents. Both the Western blotting analysis and immunofluorescence labeling techniques were used to examine the expression of NCX3.

Results:

NCX currents were decreased in rats after febrile convulsion. Compared to the control group, NCX3 expression was decreased by about 40% and 50% in the hippocampus and cerebrocortex of convulsion-prone rats, respectively. Furthermore, the extent of reduction in NCX3 expression seemed to correlate with the number of seizures.

Conclusions:

There is a significant reduction in NCX3 expression in rats with febrile convulsions. Our findings also indicate a potential link between NCX3 expression, febrile convulsion in early childhood, and adult onset of epilepsy.     

Proteomic Analysis for Finding Serum Pathogenic Factors and Potential Biomarkers in Multiple Myeloma

Background:

Multiple myeloma (MM) is a malignant tumor, which takes the second place in malignant blood disease. The clinical symptoms are complicated that make more difficult to diagnose and therapy. Lots of researches focus on the proteins about MM in order to solve those problems. We used proteomic methods to find potential biomarkers in MM patients.

Methods:

We applied the peptide ligand library beads (PLLBs) to deplete high abundance proteins in serum for finding potential pathogenic factors and biomarkers of MM. Using 1D-Gel-liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified 789 and 849 unique serum proteins in MM patients and in healthy controls, respectively.

Results:

Twenty-two proteins were found differentially expressed between the two groups including serum amyloid A protein, vitamin D-binding protein isoform-1 precursor, plasma kallikrein, and apolipoprotein A-I. Changes of integrin alpha-11 and isoform-1 of multimerin-1 were validated with Western blotting. The linkage of the differentially expressed proteins and the pathogenesis pathways of MM were discussed.

Conclusions:

PLLB combined with 1D-gel-LC-MS/MS analysis is an efficient method to identify differentially expressed proteins in serum from patients with MM.     

Embryonic Stem Cells-loaded Gelatin Microcryogels Slow Progression of Chronic Kidney Disease

Background:

Chronic kidney disease (CKD) has become a public health problem. New interventions to slow or prevent disease progression are urgently needed. In this setting, cell therapies associated with regenerative effects are attracting increasing interest. We evaluated the effect of embryonic stem cells (ESCs) on the progression of CKD.

Methods:

Adult male Sprague–Dawley rats were subjected to 5/6 nephrectomy. We used pedicled greater omentum flaps packing ESC-loaded gelatin microcryogels (GMs) on the 5/6 nephrectomized kidney. The viability of ESCs within the GMs was detected using in vitro two-photon fluorescence confocal imaging. Rats were sacrificed after 12 weeks. Renal injury was evaluated using serum creatinine, urea nitrogen, 24 h protein, renal pathology, and tubular injury score results. Structural damage was evaluated by periodic acid-Schiff and Masson trichrome staining.

Results:

In vitro, ESCs could be automatically loaded into the GMs. Uniform cell distribution, good cell attachment, and viability were achieved from day 1 to 7 in vitro. After 12 weeks, in the pedicled greater omentum flaps packing ESC-loaded GMs on 5/6 nephrectomized rats group, the plasma urea nitrogen levels were 26% lower than in the right nephrectomy group, glomerulosclerosis index was 62% lower and tubular injury index was 40% lower than in the 5/6 nephrectomized rats group without GMs.

Conclusions:

In a rat model of established CKD, we demonstrated that the pedicled greater omentum flaps packing ESC-loaded GMs on the 5/6 nephrectomized kidney have a long-lasting therapeutic rescue function, as shown by the decreased progression of CKD and reduced glomerular injury.     

Conditional Knockout of Src Homology 2 Domain-containing Protein Tyrosine Phosphatase-2 in Myeloid Cells Attenuates Renal Fibrosis after Unilateral Ureter Obstruction

Background:

Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) is a kind of intracellular protein tyrosine phosphatase. Studies have revealed its roles in various disease, however, whether SHP-2 involves in renal fibrosis remains unclear. The aim of this study was to explore the roles of myeloid cells SHP-2 in renal interstitial fibrosis.

Methods:

Myeloid cells SHP-2 gene was conditionally knocked-out (CKO) in mice using loxP-Cre system, and renal interstitial fibrosis was induced by unilateral ureter obstruction (UUO). The total collagen deposition in the renal interstitium was assessed using picrosirius red stain. F4/80 immunostaing was used to evaluate macrophage infiltration in renal tubular interstitium. Quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay were used to analyze the production of cytokines in the kidney. Transferase-mediated dUTP nick-end labeling stain was used to assess the apoptotic renal tubular epithelial cells.

Results:

Src homology 2 domain-containing protein tyrosine phosphatase-2 gene CKO in myeloid cells significantly reduced collagen deposition in the renal interstitium after UUO. Macrophage infiltration was evidently decreased in renal tubular interstitium of SHP-2 CKO mice. Meanwhile, the production of pro-inflammatory cytokines was significantly suppressed in SHP-2 CKO mice. However, no significant difference was observed in the number of apoptotic renal tubular epithelial cells between wild-type and SHP-2 CKO mice.

Conclusions:

Our observations suggested that SHP-2 in myeloid cells plays a pivotal role in the pathogenesis of renal fibrosis, and that silencing of SHP-2 gene in myeloid cells may protect renal from inflammatory damage and prevent renal fibrosis after renal injury.