Combination of a bronchogenic cyst in the thoracic spinal canal with chronic myelocytic leukemia.

The presented case report describes an incredibly rare instance of an intramedullary bronchial cyst located in the thoracic spinal canal on the dorsal side of the spinal cord, which was observed in a patient with chronic myelogenous leukemia. A 29-year-old man presented with back pain for half a month, along with numbness and pain below the chest and ribs for 1 week. Hypersensitivity was present in the inferior plane of the long xiphoid process in the nervous system. Magnetic resonance imaging (MRI) showed intramedullary cystic lesions in the vertebral body plane of the third to the fourth thoracic vertebra. There was no recurrence during the 6-month postoperative follow-up period. The histopathological findings were consistent with bronchogenic cysts. Cystic lesions were eliminated through the posterior median approach. After the cyst ruptured during surgery, gel liquid was seen, and the majority of the cyst walls were removed. One week after the surgery, the hypersensitivity fully subsided. Six months following surgery, an updated MRI revealed no recurrence. Intramedullary bronchogenic cysts on the dorsal side of the thoracic spine are extremely uncommon. Diagnosis requires histopathological evidence, and it is challenging to diagnose before surgery. Prompt surgical resection is recommended in case of positive diagnosis.

BMI1 activates P-glycoprotein via transcription repression of miR-3682-3p and enhances chemoresistance of bladder cancer cell.

Chemoresistance is the most significant reason for the failure of cancer treatment following radical cystectomy. The response rate to the first-line chemotherapy of cisplatin and gemcitabine does not exceed 50%. In our previous research, elevated BMI1 (B-cell specific Moloney murine leukemia virus integration region 1) expression in bladder cancer conferred poor survival and was associated with chemoresistance. Herein, via analysis of The Cancer Genome Atlas database and validation of clinical samples, BMI1 was elevated in patients with bladder cancer resistant to cisplatin and gemcitabine, which conferred tumor relapse and progression. Consistently, BMI1 was markedly increased in the established cisplatin- and gemcitabine-resistant T24 cells (T24/DDP&GEM). Functionally, BMI1 overexpression dramatically promoted drug efflux, enhanced viability and decreased apoptosis of bladder cancer cells upon treatment with cisplatin or gemcitabine, whereas BMI1 downregulation reversed this effect. Mechanically, upon interaction with p53, BMI1 was recruited on the promoter of miR-3682-3p gene concomitant with an increase in the mono-ubiquitination of histone H2A lysine 119, leading to transcription repression of miR-3682-3p gene followed by derepression of ABCB1 (ATP binding cassette subfamily B member 1) gene. Moreover, suppression of P-glycoprotein by miR-3682-3p mimics or its inhibitor XR-9576, could significantly reverse chemoresistance of T24/DDP&GEM cells. These results provided a novel insight into a portion of the mechanism underlying BMI1-mediated chemoresistance in bladder cancer.

Comprehensive signature analysis of drug metabolism differences in the White, Black and Asian prostate cancer patients.

The drug response sensitivity and related prognosis of prostate cancer varied from races, while the original mechanism remains rarely understood. In this study, the comprehensive signature including transcriptomics, epigenome and single nucleotide polymorphisms (SNPs) of 485 PCa cases- including 415 Whites, 58 Blacks and 12 Asians from the TCGA database were analyzed to investigate the drug metabolism differences between races. We found that Blacks and Whites had a more prominent drug metabolism, cytotoxic therapy resistance, and endocrine therapy resistance than Asians, while Whites were more prominent in drug metabolism, cytotoxic therapy resistance and endocrine therapy resistance than Blacks. Subsequently, the targeted regulation analysis indicated that the racial differences in cytotoxic therapy resistance, endocrine therapy resistance, might originate from drug metabolisms, and 19 drug metabolism-related core genes were confirmed in the multi-omics network for subsequent analysis. Furthermore, we verified that CYP1A1, CYP3A4, CYP2B6, UGT2B17, UGT2B7, UGT1A8, UGT2B11, GAS5, SNHG6, XIST significantly affected antineoplastic drugs sensitivities in PCa cell lines, and these genes also showed good predictive efficiency of drug response and treatment outcomes for PCa in this cohort of patients. These findings revealed a comprehensive signature of drug metabolism differences for the Whites, Blacks and Asians, and it may provide some evidence for making individualized treatment strategies.

Novel Chiral Thiourea Derived from Hydroquinine and l-Phenylglycinol: An Effective Catalyst for Enantio- and Diastereoselective Aza-Henry Reaction.

A series of chiral thiourea bearing multiple H-bond donors derived from hydroquinine has been reported. The aza-Henry reaction of isatin-derived ketimines and long-chain nitroalkanes catalyzed by these chiral thioureas can achieve high enantioselectivity (78-99% ee) and excellent diastereoselectivity (up to 99:1). This work is the first report on long-chain nitroalkanes as substrates with excellent diastereoselectivity in metal-free catalytic systems.

Determination of vascular alteration in smokers by quantitative computed tomography measurements.

A new method of quantitative computed tomography (CT) measurements of pulmonary vessels are applicable to morphological studies and may be helpful in defining the progression of emphysema in smokers. However, limited data are available on the relationship between the smoking status and pulmonary vessels alteration established in longitudinal observations. Therefore, we investigated the change of pulmonary vessels on CTs in a longitudinal cohort of smokers.Chest CTs were available for 287 current smokers, 439 non-smokers, and 80 former smokers who quit smoking at least 2 years after the baseline CT. CT images obtained at the baseline and 1 year later were assessed by a new quantitative CT measurement method, computing the total number of pulmonary vessels (TNV), mean lung density (MLD), and the percentage of low-attenuation areas at a threshold of -950 (density attenuation area [LAA]%950). Analysis of variance (ANOVA) and the independent sample t test were used to estimate the influence of the baseline parameters. The t paired test was employed to evaluate the change between the baseline and follow-up results.The current smokers related to have higher whole-lung MLD, as well as less and lower TNV values than the non-smokers (P <.05). But no significant differences in LAA%950 were found between smokers and non-smokers. After one year, the increase in LAA%950 was more rapid in the current (additional 0.3% per year, P <. 05-.01) than in the former smokers (additional 0.2% per year, P = .3). Additionally, the decline in TNV was faster in the current (additional -1.3 per year, P <.05-.01) than that in the former smokers (additional -0.2 per year, P = .6). Current smoke, pack-years, weight, and lung volume independently predicted TNV at baseline (P <.001) in multivariate analysis.The findings of this study reveal that the decline in the pulmonary vessels in smokers can be measured and related to their smoking status.

Spectral CT Imaging in the Differential Diagnosis of Small Bowel Adenocarcinoma From Primary Small Intestinal Lymphoma.

PURPOSE: To investigate the value of dual-energy spectral computed tomography (CT) imaging in the differential diagnosis of small bowel adenocarcinoma (SBA) from primary small intestinal lymphoma (PSIL). MATERIALS AND METHODS: We retrospectively analyzed the images of 27 SBA cases and 15 PSIL cases. These patients underwent spectral CT imaging in the arterial phase (AP) and venous phase (VP). CT attenuation values of tumors at different energy levels were measured to generate spectral attenuation curve and to calculate curve slope (λHU). Iodine concentration (IC) in tumors at AP and VP were measured and normalized to that of aorta as normalized iodine concentration (NIC). Independent samples t test was used to analyze the spectral CT parameters; Receiver operating characteristic curves were generated to evaluate the diagnostic efficacy of each parameter. RESULTS: There were significant differences between SBA and PSIL in IC (2.09 ± 0.71 vs 1.33 ± 0.15 mg/ml), NIC (0.20 ± 0.06 vs 0.13 ± 0.02) and slope (λHU) (2.78 ± 1.06 vs 1.86 ± 0.30) in AP and (1.86 ± 0.68 vs 1.37 ± 0.18 mg/ml for IC; 0.47 ± 0.13 vs 0.33 ± 0.02 for NIC and 2.00 ± 0.56 vs 1.50 ± 0.26 for λHU) in VP (all p < 0.05). For the CT value measurement, there were significant differences between SBA and PSIL in the 40-60keV energy range (p < 0.05), but not in the 70-140keV range (p > 0.05). Using 1.38 mg/ml as a threshold value for iodine concentration at AP, one could obtain the area-under-curve of 0.93 for receiver operating characteristic study and sensitivity of 94% and specificity of 85% for differentiating SBA from PSIL. The sensitivity and specificity values were significantly higher than the respective values of 62% and 60% with the conventional CT numbers at 70keV. CONCLUSION: Quantitative parameters obtained in spectral CT, especially iodine concentration in AP, provide high accuracy for differentiating SBA from PSIL.

TEM8 functions as a receptor for uPA and mediates uPA-stimulated EGFR phosphorylation.

BACKGROUND: TEM8 is a cell membrane protein predominantly expressed in tumor endothelium, which serves as a receptor for the protective antigen (PA) of anthrax toxin. However, the physiological ligands for TEM8 remain unknown. RESULTS: Here we identified uPA as an interacting partner of TEM8. Binding of uPA stimulated the phosphorylation of TEM8 and augmented phosphorylation of EGFR and ERK1/2. Finally, TEM8-Fc, a recombinant fusion protein comprising the extracellular domain of human TEM8 linked to the Fc portion of human IgG1, efficiently abrogated the interaction between uPA and TEM8, blocked uPA-induced migration of HepG2 cells in vitro and inhibited the growth and metastasis of human MCF-7 xenografts in vivo. uPA, TEM8 and EGFR overexpression and ERK1/2 phosphorylation were found co-located on frozen cancer tissue sections. CONCLUSIONS: Taken together, our data provide evidence that TEM8 is a novel receptor for uPA, which may play a significant role in the regulation of tumor growth and metastasis.

Image quality comparison of two adaptive statistical iterative reconstruction (ASiR, ASiR-V) algorithms and filtered back projection in routine liver CT.

OBJECTIVE: To compare image quality of two adaptive statistical iterative reconstruction (ASiR and ASiR-V) algorithms using objective and subjective metrics for routine liver CT, with the conventional filtered back projection (FBP) reconstructions as reference standards. METHODS: This institutional review board-approved study included 52 patients with clinically suspected hepatic metastases. Patients were divided equally into ASiR and ASiR-V groups with same scan parameters. Images were reconstructed with ASiR and ASiR-V from 0 (FBP) to 100% blending percentages at 10% interval in its respective group. Mean and standard deviation of CT numbers for liver parenchyma were recorded. Two experienced radiologists reviewed all images for image quality blindly and independently. Data were statistically analyzed. RESULTS: There was no difference in CT dose index between ASiR and ASiR-V groups. As the percentage of ASiR and ASiR-V increased from 10 to 100% , image noise reduced by 8.6 -57.9% and 8.9-81.6%, respectively, compared with FBP. There was substantial interobserver agreement in image quality assessment for ASiR and ASiR-V images. Compared with FBP reconstruction, subjective image quality scores of ASiR and ASiR-V improved significantly as percentage increased from 10 to 80% for ASiR (peaked at 50% with 32.2% noise reduction) and from 10 to 90% (peaked at 60% with 51.5% noise reduction) for ASiR-V. CONCLUSION: Both ASiR and ASiR-V improved the objective and subjective image quality for routine liver CT compared with FBP. ASiR-V provided further image quality improvement with higher acceptable percentage than ASiR, and ASiR-V60% had the highest image quality score. Advances in knowledge: (1) Both ASiR and ASiR-V significantly reduce image noise compared with conventional FBP reconstruction. (2) ASiR-V with 60 blending percentage provides the highest image quality score in routine liver CT.

SPK1-transfected UCMSC has better therapeutic activity than UCMSC in the treatment of experimental autoimmune encephalomyelitis model of Multiple sclerosis.

Multiple Sclerosis (MS), is a chronic inflammatory autoimmune disorder of the central nervous system that leads to chronic demyelination with axonal damage and neuronal loss. Mesenchymal stem cells (MSCs) represent a promising therapeutic approach for MS. In the current study, we investigated the effects of MSCs derived from the human umbilical cord (UCMSC) transfected by sphingosine kinase 1 (SPK1) gene. All the results showed that transplantation of UCMSCs gene modified by SPK1 (UCMSC-SPK1) dramatically reduce the severity of neurological deficits of the experimental autoimmune encephalomyelitis (EAE) mice, paralleling by reductions in demyelination, axonal loss, and astrogliosis. UCMSC-SPK1 transplantation also could inhibit the development of natural killer (NK) responses in the spleen of EAE mice, and increase the ratio of CD4+ CD25+ FoxP3+ (Treg) T cells. Furthermore, we described that a shift in the cytokine response from Th1/Th17 to Th2 was an underlying mechanism that suppressed CNS autoimmunity. UCMSCs transfected by SPK1 gene potentially offer a novel mode for the treatment of MS, and the specific mechanism of SPK1 in treating MS/EAE.

Dual energy spectral CT imaging for the evaluation of small hepatocellular carcinoma microvascular invasion.

OBJECTIVE: To study the clinical value of dual-energy spectral CT in the quantitative assessment of microvascular invasion of small hepatocellular carcinoma. METHODS: This study was approved by our ethics committee. 50 patients with small hepatocellular carcinoma who underwent contrast enhanced spectral CT in arterial phase (AP) and portal venous phase (VP) were enrolled. Tumour CT value and iodine concentration (IC) were measured from spectral CT images. The slope of spectral curve, normalized iodine concentration (NIC, to abdominal aorta) and ratio of IC difference between AP and VP (RICAP-VP: [RICAP-VP=(ICAP-ICVP)/ICAP]) were calculated. Tumours were identified as either with or without microvascular invasion based on pathological results. Measurements were statistically compared using independent samples t test. The receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of tumours microvascular invasion assessment. The 70keV images were used to simulate the results of conventional CT scans for comparison. RESULTS: 56 small hepatocellular carcinomas were detected with 37 lesions (Group A) with microvascular invasion and 19 (Group B) without. There were significant differences in IC, NIC and slope in AP and RICAP-VP between Group A (2.48±0.70mg/ml, 0.23±0.05, 3.39±1.01 and 0.28±0.16) and Group B (1.65±0.47mg/ml, 0.15±0.05, 2.22±0.64 and 0.03±0.24) (all p<0.05). Using 0.188 as the threshold for NIC, one could obtain an area-under-curve (AUC) of 0.87 in ROC to differentiate between tumours with and without microvascular invasion. AUC was 0.71 with CT value at 70keV and improved to 0.81 at 40keV. CONCLUSION: Dual-energy Spectral CT provides additional quantitative parameters than conventional CT to improve the differentiation between small hepatocellular carcinoma with and without microvascular invasion. CLINICAL APPLICATION/RELEVANCE: Quantitative iodine concentration measurement in spectral CT may be used to provide a new method to improve the evaluation for small hepatocellular carcinoma microvascular invasion.

Clinical Application of Dual-Energy Spectral Computed Tomography in Detecting Cholesterol Gallstones From Surrounding Bile.

RATIONALE AND OBJECTIVE: This study aimed to investigate the clinical value of spectral computed tomography (CT) in the detection of cholesterol gallstones from surrounding bile. MATERIALS AND METHODS: This study was approved by the institutional review board. The unenhanced spectral CT data of 24 patients who had surgically confirmed cholesterol gallstones were analyzed. Lipid concentrations and CT numbers were measured from fat-based material decomposition image and virtual monochromatic image sets (40-140 keV), respectively. The difference in lipid concentration and CT number between cholesterol gallstones and the surrounding bile were statistically analyzed. Receiver operating characteristic analysis was applied to determine the diagnostic accuracy of using lipid concentration to differentiate cholesterol gallstones from bile. RESULTS: Cholesterol gallstones were bright on fat-based material decomposition images yielding a 92% detection rate (22 of 24). The lipid concentrations (552.65 ± 262.36 mg/mL), CT number at 40 keV (-31.57 ± 16.88 HU) and 140 keV (24.30 ± 5.85 HU) for the cholesterol gallstones were significantly different from those of bile (-13.94 ± 105.12 mg/mL, 12.99 ± 9.39 HU and 6.19 ± 4.97 HU, respectively). Using 182.59 mg/mL as the threshold value for lipid concentration, one could obtain sensitivity of 95.5% and specificity of 100% with accuracy of 0.994 for differentiating cholesterol gallstones from bile. CONCLUSIONS: Virtual monochromatic spectral CT images at 40 keV and 140 keV provide significant CT number differences between cholesterol gallstones and the surrounding bile. Spectral CT provides an excellent detection rate for cholesterol gallstones.

Adipose-Derived Mesenchymal Stem Cells Ameliorate Lipid Metabolic Disturbance in Mice.

UNLABELLED: : Adipose-derived mesenchymal stem cells (AD-MSCs) have been shown to ameliorate hyperglycemia in diabetic animals and individuals. However, little is known about whether AD-MSCs affect lipid metabolism. Here we have demonstrated for the first time that AD-MSC infusion can significantly suppress the increase in body weight and remarkably improve dyslipidemia in db/db obese mice and diet-induced obesity mice. Induction of white fat tissue "browning" and activation of adenosine monophosphate-activated protein kinase and its downstream hormone-sensitive lipase in adipose tissue contribute to the antiobesity and lipid-lowering effects. Thus, AD-MSC infusion holds great therapeutic potential for dyslipidemia and associated cardiovascular diseases. SIGNIFICANCE: Mesenchymal stem cells (MSCs) are considered one of the most promising types of stem cells for translational application because of their rich tissue sources, multilineage differentiation capacity, and easy amplification in vitro and unique immunobiological properties. This study demonstrated that adipose-derived MSCs (AD-MSCs) infusion can significantly suppress the increase in body weight and remarkably improve dyslipidemia in obese mice. Induction of white fat tissue "browning" and activation of adenosine monophosphate-activated protein kinase and its downstream hormone-sensitive lipase in adipose tissue were demonstrated to contribute to the antiobesity and lipid-lowering effects. Thus, AD-MSC infusion holds great therapeutic potential for dyslipidemia.

[Transfection Efficiency of Ad5F11p-GFP on CIK and NK-92 Cells and Its Influence on Biological Characteristics].

OBJECTIVE: To study transfection efficiency of Ad5F11p-GFP and its influence on biological characteristics of CIK and NK-92 cells in order to predict the application of Ad5F11p vector in immunotherapy. METHODS: Two kinds of immune cells, cytokine-induced killer (CIK) cells and natural-killer (NK) cell line NK-92 cells, were transfected by Ad5F11p-GFP at different multiplicity of transfection (MOI), and untransfected immune cells were used as negative control. GFP expression was determined by flow cytometry, the cell morphology was observed with microscope, the cell proliferation was analyzed by trypan blue staining, specific cytotoxicity of NK-92 cells was determined by LDH assay. RESULTS: About 90% of transfection efficiency for NK-92 cells could be achieved at a MOI of 25, while the transfection efficiency for CIK was less than 40% at a MOI of 200. In addition, the transfection efficiency basically unchanged at the same MOI for 48 h and 96 h, and the immune cells transfected with the virus trended to form agglomeration, displaying slower proliferation, increase of IFN-γ release and enhancement of tumor killing activity. CONCLUSION: Ad5F11p- modified NK-92 shows a good prospect for adoptive immunotherapy.

Neuroprotective effects of human umbilical cord-derived mesenchymal stromal cells combined with nimodipine against radiation-induced brain injury through inhibition of apoptosis.

BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) possess the ability to repair brain injuries. Additionally, nimodipine is a neuroprotective agent that increases cerebral blood flow and may help with the homing of MSCs to the injury site. Here we investigate the effectiveness of a combined human umbilical cord-derived MSCs and nimodipine therapy in radiation-induced brain injury (RIBI). METHODS: Female mice received whole brain irradiation (WBI) and were treated with saline, nimodipine, hUC-MSCs, or hUC-MSCs combined with nimodipine. Body weight was measured weekly. An open field test for locomotor activity and a step-down avoidance test for learning and memory function were conducted at week 4 and week 12 post-WBI. The histological damage was evaluated by hematoxylin and eosin staining and glial fibrillary acidic protein immunohistochemistry. Quantitative polymerase chain reaction and Western blotting were used to detect apoptosis-related mediators (p53, Bax and Bcl-2). RESULTS: In mice receiving the hUC-MSCs or the combined treatment, their body weight recovered, their locomotor and cognitive ability improved, and the percentage of necrotic neurons and astrocytes was reduced. The combined therapy was significantly (P < 0.05) more effective than hUC-MSCs alone; these mice showed decreased expression of pro-apoptotic indicators (p53, Bax) and increased expression of an anti-apoptotic indicator (Bcl-2), which may protect brain cells. CONCLUSIONS: We demonstrated that hUC-MSCs therapy helps recover body weight loss and behavior dysfunction in a mice model of RIBI. Moreover, the effectiveness of the combined hUC-MSCs and nimodipine therapy is due to apoptosis inhibition and enhancing homing of MSCs to the injured brain.

Aggregation of Ribosomal Protein S6 at Nucleolus Is Cell Cycle-Controlled and Its Function in Pre-rRNA Processing Is Phosphorylation Dependent.

Ribosomal protein S6 (rpS6) has long been regarded as one of the primary r-proteins that functions in the early stage of 40S subunit assembly, but its actual role is still obscure. The correct forming of 18S rRNA is a key step in the nuclear synthesis of 40S subunit. In this study, we demonstrate that rpS6 participates in the processing of 30S pre-rRNA to 18S rRNA only when its C-terminal five serines are phosphorylated, however, the process of entering the nucleus and then targeting the nucleolus does not dependent its phosphorylation. Remarkably, we also find that the aggregation of rpS6 at the nucleolus correlates to the phasing of cell cycle, beginning to concentrate in the nucleolus at later S phase and disaggregate at M phase. J. Cell. Biochem. 117: 1649-1657, 2016. © 2015 Wiley Periodicals, Inc.

Short-term memory of danger signals or environmental stimuli in mesenchymal stem cells: implications for therapeutic potential.

Mesenchymal stem/stromal cells (MSCs) possess some characteristics of immune cells, including a pro-inflammatory phenotype, an immunosuppressive phenotype, antibacterial properties and the expression of Toll-like receptor proteins. Here we show that, similar to immune cells, MSCs retain information from danger signals or environmental stimuli for a period of time. When treated with the pro-inflammatory factors lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α), MSCs display increased expression of IL-6, IL-8 and MCP-1. Following re-plating and several rounds of cell division in the absence of stimulating factors, the expression of IL-6, IL-8 and MCP-1 remained higher than in untreated cells for over 7 days. A spike in cytokine secretion occurred when cells were exposed to a second round of stimulation. We primed MSCs with LPS and LPS-primed MSCs had better therapeutic efficacy at promoting skin flap survival in a diabetic rat model than did unprimed MSCs. Finally, we found that several microRNAs, including miR146a, miR150 and miR155, along with the modification of DNA by 5-hydroxymethylcytosine (5hmC), mediate the MSC response to LPS and TNF-α stimulation. Collectively, our data suggest that MSCs have a short-term memory of environmental signals, which may impact their therapeutic potential.

IL-6 secreted from senescent mesenchymal stem cells promotes proliferation and migration of breast cancer cells.

Human mesenchymal stem cells (hMSCs) are currently investigated for a variety of therapeutic applications. However, MSCs isolated from primary tissue cannot meet clinical grade needs and should be expanded in vitro for several passages. Although hMSCs show low possibility for undergoing oncogenic transformation, they do, similar to other somatic cells, undergo cellular senescence and their therapeutic potential is diminished when cultured in vitro. However, the role of senescent MSCs in tumor progression remains largely elusive. In the current study, by establishing senescent human umbilical cord mesenchymal stem cells (s-UCMSCs) through the replicative senescence model and genotoxic stress induced premature senescence model, we show that s-UCMSCs significantly stimulate proliferation and migration of breast cancer cells in vitro and tumor progression in a co-transplant xenograft mouse model compared with 'young' counterparts (defined as MSCs at passage 5, in contrast to senescent MSCs at passage 45). In addition, we identified IL-6, a known pleiotropic cytokine, as a principal mediator for the tumor-promoting activity of s-UCMSCs by induction of STAT3 phosphorylation. Depletion of IL-6 from s-UCMSCs conditioned medium partially abrogated the stimulatory effect of s-UCMSCs on the proliferation and migration of breast tumor cells.

Differentiation of hUC-MSC into dopaminergic-like cells after transduction with hepatocyte growth factor.

Parkinson's disease (PD) is a common neurodegenerative condition causing significant disability and thus negatively impacting quality of life. The recent advent of stem cell-based therapy has heralded the prospect of a potential restorative treatment option for PD. In particular, mesenchymal stem cells derived from human umbilical cord (hUC-MSCs) have great potential for developing a therapeutic agent as such. Furthermore, hepatocyte growth factor (HGF), which shows mitogenic and morphogenetic activities in a variety of cells, including MSC, and may be implicated in the pathophysiology of PD. As such, HGF may represent a new therapeutic target for the disease. In this study, we successfully isolated and facilitated the transduction of an adenoviral vector expressing HGF (Ad-HGF) into isolated hUC-MSCs. Following transduction, the hUC-MSCs can differentiate into dopaminergic neuron-like cells secreting dopamine, tyrosine hydroxylase, and dopamine transporter. Our data suggest that hUC-MSCs have the ability to differentiate into dopaminergic neurons after transduction with Ad-HGF, providing encouraging evidence to further explore this approach to the treatment of PD.

[2-DG enhances TRAIL-induced apoptosis of leukemia HL-60 cells].

This study was purposed to investigate the effects of 2-deoxy-D-glucose (2-DG) on sensitizing HL-60 cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis and its possible mechanism. The proliferative inhibition of HL-60 cells treated with different concentrations of 2-DG and TRAIL was measured by MTT assay. The cells were treated with 2-DG, TRAIL, and 2-DG combined with TRAIL at the concentration < IC50 value, i.e. 10 mmol/L for 2-DG and 100 ng/ml for TRAIL. Apoptosis was analyzed by flow cytometry with PI staining; the expression of RIP1, GRP78, and PARP was analyzed by Western blot; the activity of caspase-3 was detected by special detection kit. The results showed that the combined treatment of HL-60 cells for 48 h induced an apoptotic rate of (45.1 ± 4.3)%, which was significantly higher than that of treated with 2-DG or TRAIL alone; at the same time, the combined treatment potentiated the expression of GRP78 and caspase-3 activity, and down-regulated the expression of RIP1. It is concluded that 2-DG can sensitize HL-60 cells to TRAIL-induced apoptosis, which may be correlated with excessive endoplasmic reticulum stress response, down-regulation of RIP1, and increase of caspase-3 activity.

Attenuated Salmonella typhimurium carrying the hepatocyte growth factor and keratinocyte growth factor genes repairs gastrointestinal mucosal damage caused by chemotherapy.

Radiotherapy and chemotherapy are the main therapeutic approaches for patients with malignant tumours, especially advanced tumours. However, they can cause adverse effects, one of which is gastrointestinal mucosal damage, which can greatly affect patients' quality of life. Until now, there have been no effective therapies to avoid or treat these adverse effects. In this study, we used attenuated Salmonella typhimurium (S. typhimurium) to deliver the hepatocyte growth factor (HGF) or keratinocyte growth factor (KGF) to murine gastrointestinal mucosa. We found that attenuated S. typhimurium carrying the HGF or KGF genes can effectively reduce the ratio of tumour to non-tumour carcass weight, repair damage to the gastrointestinal mucosal from chemotherapy, improve the immune response, and reduce the mortality rate of mice. Oral administration of attenuated S. typhimurium with HGF and KGF may be promising as a way of improving the quality of life of patients undergoing radiotherapy and chemotherapy.