Journal of Huazhong University of Science and Technology [Medical Sciences]最新文献

Vasculogenic mimicry (VM) is a process by which aggressive tumor cells generate non-endothelial cell-lined channels in malignant tumors including hepatocellular carcinoma (HCC). It has provided new insights into tumor behavior and has surfaced as a potential target for drug therapy. The molecular events underlying the process of VM formation are still poorly understood. In this study, we attempted to elucidate the relationship between Notch4 and VM formation in HCC. An effective siRNA lentiviral vector targeting Notch4 was constructed and transfected into Bel7402, a HCC cell line. VM networks were observed with a microscope in a 3 dimensional cell culture system. Cell migration and invasion were evaluated using wound healing and transwell assays. Matrix metalloproteinases (MMPs) activity was detected by gelatin zymography. Furthermore, the role of Notch4 inhibition in Bel7402 cells in vivo was examined in subcutaneous xenograft tumor model of mice. The results showed that downregulation of Notch4 destroyed VM network formation and inhibited migration and invasion of tumor cells in vitro (P<0.05). In vivo, tumor growth was also inhibited in subcutaneous xenograft model (P<0.05). The potential mechanisms might be related with down-regulation of MT1-MMP, MMP-2, MMP-9 expression and inhibition of the activation of MMP2 and MMP9. These results indicated that Notch4 may play an important role in VM formation and tumor invasion in HCC. Related molecular pathways may be used as novel therapeutic targets for HCC antiangiogenesis therapy.

Current treatments for cancer and the central nervous system diseases are limited, partly due to the difficulties posed by the insolubility, poor distribution of drugs among cells and lack of selectivity of drugs, the inability of drugs to cross cellular barriers and blood brain barrier (BBB). Carbon nanotubes (CNTs) possess many distinct properties including good electronic properties, remarkably penetrating capability on the cell membrane, high drug-loading and pH-dependent therapeutic unloading capacities, thermal properties, large surface area and easy modification with molecules, which render them as a suitable candidate to deliver drugs to cancer and brain. CNTs as a drug delivery could achieve a high efficacy, enhance specificity and diminish side effects. Whereas CNTs have been primarily employed in cancer treatment, a few studies have focused on the treatment and diagnosis of the central nervous system diseases using CNTs. Here, we review the current progress of in vitro and in vivo researches of CNTs-based drug delivery to cancer involving CNTs-based tumor-targeted drug delivery systems (DDS), photodynamic therapy (PDT) and photothermal therapy (PTT). Meanwhile, we also review the current progress of in vitro and in vivo researches of CNTs-based drug delivery to brain.

HBV-associated acute-on-chronic liver failure is prevalent in mainland China. The prognosis of HBV-ACLF is poor. The mortality of HBV-ACLF is approximately 80%. Therefore, a prognostic indicator was needed in order to allow us to intervene as soon as possible. The model for end-stage liver disease (MELD) scoring system is widely used to predict the prognosis of liver failure. However, the assessment is too complex to restrict its application. This study aimed to investigate the expression of IP-10 in peripheral blood mononuclear cells (PBMC), in order to explore the relationship between the expression and prognosis of patients with HBV-ACLF. The mRNA level of IP-10 in PBMCs were analyzed in 80 patients with HBV-ACLF, 40 patients with chronic hepatitis B (CHB) and 40 healthy people by fluorescent quantitative PCR. IP-10 mRNA level was significantly higher in the HBV-ACLF group than in the other two groups (P<0.01). Group with MELD score below 30 had lower IP-10 mRNA level than group with MELD score over 30 (P<0.05). The IP-10 mRNA level in PBMCs in positive group was higher than that in negative group (P<0.01). With a threshold of 0.925, the area under the receiver operating characteristic (ROC) curves was 0.815. These findings suggest that assessment of IP-10 mRNA level in the PBMCs would be helpful for evaluating the disease severity and prognosis in patients with HBV-ACLF.

To investigate the role of signaling pathway in the effect of endoplasmic reticulum stress (ER stress) in endothelial cells stimulated with cigarette smoke extract (CSE). Human umbilical vein endothelial cells (HUVECs) were cultured and divided into 3 groups: CSE-stimulated group, CSE-stimulated with 4-PBA group, and negative control group. HUVECs were cultured and stimulated with CSE at concentrations of 5%, 10% and 20%, respectively, mRNA of CXCL-8 and GRP78 was detected by real-time PCR. ELISA was performed to test the expression of CXCL-8 protein, and neutrophils migration was detected by Transwell board test. The NF-κB, ERK, p38MAPK and transforming growth factor beta (TGF-β) were detected by flow cytometry. The mRNA of CXCL-8 and GRP78 increased in CSE-stimulated HUVECs (P<0.05). Furthermore, it was concentration-dependent. 4-PBA significantly reduced the expression of CXCL-8 protein (P<0.05) and neutrophil migration (P<0.05). The TGF-β, rather than the NF-κB, ERK and P38MAPK pathway might be involved in ER stress stimulated by CSE. CSE induced neutrophils migration by increasing the expression of CXCL-8 in endothelial cells. ER stress might play a role in the effect of neutrophils migration stimulated with CSE, and TGF-β pathway may contribute to the ER stress in HUVECs.

The effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) on potassium- chloride cotransporter-2 (KCC2) protein expression following spinal cord injury (SCI) and the action mechanism were investigated. SCI models were established in SD rats. Five groups were set up randomly: normal control group, SCI 7-day (7D) model group, SCI 14-day (14D) model group, SCI-7D rTMS group and SCI-14D rTMS group (n=5 each). The rats in SCI rTMS groups were treated with 10 Hz rTMS from 8th day and 15th day after SCI respectively, once every day, 5 days every week, a total of 4 weeks. After the model establishment, motor recovery and spasticity alleviation were evaluated with BBB scale once a week till the end of treatment. Finally, different parts of tissues were dissected out for detection of variations of KCC2 protein using Western blotting and polymerase chain reaction (PCR) technique. The results showed that the BBS scores after treatment were significantly higher in SCI-7D rTMS group than in SCI-14D rTMS group (P<0.05). As compared with normal control groups, The KCC2 protein in SCI model groups was down-regulated after SCI, and the decrease was much more significant in SCI-14D model group than in SCI-7D group (P<0.05). As compared with SCI model groups, KCC2 protein in rTMS groups was up-regulated after the treatment (P<0.05). The up-regulation of KCC2 protein content and expression was more obvious in SCI-7D rTMS group than in SCI-14D rTMS group (P<0.05). It was concluded that 10 Hz rTMS can alleviate spasticity in rats with SCI, which might be attributed to the up-regulation of KCC2 protein. It was also suggested that the high-frequency rTMS treatment after SCI at early stage might achieve more satisfactory curative effectiveness.

The aim of the present study was to examine the relationship between the protein expression of vascular endothelial growth factor (VEGF) and lymph node metastasis (LNM) in papillary thyroid cancer (PTC). VEGF-related articles that had been published until August 2016 were searched from the PubMed, EMBASE, and MEDLINE to identify the risk factors of LNM in PTC. RevMan 5.3 software was used for the meta-analysis. Finally, 9 articles met the inclusion criteria and were included in our meta-analysis. LNM was found to be present in 176 of 318 patients (57.8%) with high VEGF expression and in 71 of 159 patients (47.0%) with low VEGF expression. The overall OR was 2.81 (95% confidence interval, 1.49-5.29). LNM occurred more frequently in patients with high VEGF expression than in those with low VEGF expression (P=0.001). Heterogeneity was markedly decreased in the subgroup analyses of LNM in terms of the patients' country of origin and the detection methods. Our meta- analysis concluded that the VEGF protein expression is associated with LNM in PTC.

Food intake has a great influence on blood glucose in patients with diabetes. This study was to determine the glycemic index (GI) and glycemic load (GL) of a particular pomelo named Majia pomelo and its effects on postprandial glucose (PPG) in patients with type 2 diabetes (T2D). Twenty healthy subjects and 20 T2D patients (controlled on lifestyle measures and/or metformin) were tested on 2 separate days with 50 g of glucose and 50 g equivalent of carbohydrates from Majia pomelo for GI measurement. To test effects of Majia pomelo on PPG, 19 hospitalized T2D patients (controlled on insulin therapy) were selected for a 9-day study. The dose of insulin for each patient was adjusted on the first 3 days. A total of 100 mg Majia pomelo was consumed per meal in the last 3 tested days. Blood glucose was measured to evaluate the glycemic excursions. The GIs for Majia pomelo in healthy individuals and T2D patients were 78.34±1.88 and 72.15±1.95 respectively. The value of GL was as low as 4.23 in diabetic patients with serving size of 100 g pomelo, indicting Majia pomelo as a high GI but low GL fruit. Consumption of Majia pomelo in hospitalized T2D patients did not cause significant glucose fluctuation. It was concluded that high GI pomelo can serve as a low GL fruit if it is consumed with a limited daily amount and thus can be supplied to diabetic patients. These results may mean more varieties of food choices for T2D patients.

Polycystic ovary syndrome (PCOS) is a major endocrine disorder afflicting women of reproductive age. Women with PCOS are more likely to suffer from mental health disturbances than healthy women. The "infertility" suffered by PCOS patients would also lead to mental health disturbances. Symptom Checklist 90 (SCL-90) and questionnaire which includes patients' socio-economic and demographic data were used to assess the mental health status of PCOS (n=103) and non-PCOS (n=110) infertile patients. Logistic regression analysis and t-tests were used for comparative analysis. The data demonstrated that scores of depression, interpersonal sensitivity, obsessive-compulsive, and hostility symptoms in PCOS infertile patients were significantly higher than those in the non-PCOS infertile patients (P<0.05). Logistic regression analysis revealed that acne had negative effect on mental health status (P<0.05). Secondary infertile PCOS patients were more easily to suffer from somatization, interpersonal sensitivity, obsessive-compulsive, anxiety, hostility and paranoid ideation symptoms than the primary infertile PCOS patients (P<0.05). The results suggested that the PCOS patients especially the secondary infertile PCOS patients had obvious mental health disturbances. The acne might play an importance role in the occurrence of mental health disturbances in PCOS patients. PCOS related symptoms may be risk factors of mental health status in PCOS patients with infertility. More attention should be paid to the PCOS infertile patients, and mental health therapy should be considered if necessary.

Haploinsufficiency of the runt-related transcription factor 2 (Runx2) gene is widely known to be responsible for cleidocranial dysplasia (CCD). To date, more than 190 mutations in Runx2 gene have been reported to be related to CCD. In this study, a novel mutation of Runx2 gene was observed in a female with CCD. Genomic DNA was extracted from peripheral venous blood of the proband and eleven members of her family. Genetic testing on these twelve people identified a novel missense mutation (c.895 T>C, Y299H) in exon 5 of the RUNX2 gene in the proband. This mutation results in an amino acid change at codon 895 (P.Tyr 299 His.) from a tryptophan codon (TAT) to a histidine codon (CAT). Our finding may further extend the known mutation spectrum of the RUNX2 gene, and facilitate prenatal genetic diagnosis of CCD in the future.

The intubation of conventional transesophageal echocardiography (TEE) probes into patients causes serious esophagus irritation, and thus the use of TEE probes in pediatric practice is limited. In this study, we aimed at the development of a special probe which could be inserted through the nasopharyngeal cavity into the esophagus to obtain the same high-quality echocardiography images as those obtained by conventional TEE and improve patients' experience. During the examination, the patients felt relaxed for a longer time and cooperated with the sonographers in the process of cardiac catheterization conducted in the surgery room or the intensive care unit (ICU), resulting in improved accuracy of the diagnosis and timely administration of appropriate treatment. Two years ago, Prof. Xin-fang WANG put theories into practice by inserting the probe through the nasal cavity and pharynx into the esophagus of volunteers to successfully detect the heart and great vessels at the retrocardiac space. Later, Prof. Ming-xing XIE performed the transnasal TEE examination in 12 atrial septal defect (ASD) patients and proved the safety and reliability of this method, which could become a new way for clinical diagnosis and treatment.