Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells Promote Tumor Growth Through Hedgehog Signaling Pathway.

BACKGROUND/AIMS: Mesenchymal stem/stromal cells (MSCs) are known to home to sites of tumor microenvironments where they participate in the formation of the tumor microenvironment and to interplay with tumor cells. However, the potential functional effects of MSCs on tumor cell growth are controversial. Here, we, from the view of bone marrow MSC-derived exosomes, study the molecular mechanism of MSCs on the growth of human osteosarcoma and human gastric cancer cells. METHODS: MSCs derived from human bone marrow (hBMSCs) were isolated and cultured in complete DMEM/F12 supplemented with 10% exosome-depleted fetal bovine serum and 1% penicillin-streptomycin, cell culture supernatants containing exosomes were harvested and exosome purification was performed by ultracentrifugation. Osteosarcoma (MG63) and gastric cancer (SGC7901) cells, respectively, were treated with hBMSC-derived exosomes in the presence or absence of a small molecule inhibitor of Hedgehog pathway. Cell viability was measured by transwell invasion assay, scratch migration assay and CCK-8 test. The expression of the signaling molecules Smoothened, Patched-1, Gli1 and the ligand Shh were tested by western blot and RT-PCR. RESULTS: In this study, we found that hBMSC-derived exosomes promoted MG63 and SGC7901 cell growth through the activation of Hedgehog signaling pathway. Inhibition of Hedgehog signaling pathway significantly suppressed the process of hBMSC-derived exosomes on tumor growth. CONCLUSION: Our findings demonstrated the new roles of hedgehog signaling pathway in the hBMSCs-derived exosomes induced tumor progression.

Causal effect of beta-blockers on the risk of lung cancer: a Mendelian randomization study.

Background: It remains uncertain whether there is a causal association of the use of beta-blockers (BBs) on lung cancer risk. We used a two-sample Mendelian randomization (MR) approach to identify the causal association of BBs and lung cancer risk. Methods: Twenty-two BB-related single-nucleotide polymorphisms (SNPs) were obtained from the UK Biobank as the instrumental variables (IVs). Genetic summary data information of lung cancer was extracted from the International Lung Cancer Consortium, with a total of 11,348 cases and 15,861 controls. We adopted the inverse-variance weighted (IVW) approach to conduct the MR analyses. Egger-intercept analysis was further performed as sensitivity analysis for pleiotropy evaluation. Additionally, we investigated whether BBs could causally affect the risk of lung cancer through their pharmacological effects. Results: The current IVW analysis suggested a decreased lung cancer risk in BB users [odds ratio (OR) =0.83; 95% confidence interval (CI): 0.73-0.95; P<0.01]. Results of Egger-intercept analysis demonstrated that no pleiotropy was found (P=0.94), which suggested the robustness of the causality. However, there was little evidence that pharmacological effects mediate the association between BBs and lung cancer. Conclusions: The current analysis suggested that BBs could decrease the risk of lung cancer but may be not via its pharmacological effects. Further research is in need for elucidating the underlying mechanisms.

Study on Transmission Channel and Pollution Sources Region of O3 in Qingyuan City.

Based on the Lagrange mixed single-particle trajectory model and NCEP global reanalysis meteorological data, the 72 h backward airflow trajectory in Qingyuan City in different seasons from 2018 to 2020 was analyzed by cluster analysis. Combined with the hourly average concentration data of O3, the potential source contribution factor (PSCF) analysis and concentration weighted trajectory (CWT) analysis were used to study the regional transport and possible source area of O3 in Qingyuan City and analyzed the relationship among O3 and wind speed, wind direction, NO2, and CO. The results showed that from 2018 to 2020, the most significant proportion of primary pollutants in Qingyuan City was ozone. The annual average concentration reached the highest value since monitoring in 2019. In 2020, the impact of epidemic prevention and control decreased. The daily average concentration change characteristics showed a single peak, with the highest concentration in the afternoon, the highest peak concentration in summer, followed by spring, and the lowest concentration in winter. There are differences in the concentration of O3 between different sources of airflow in Qingyuan City. The potential source contribution factor shows that the high-value covered areas are mainly in Guangzhou, Foshan, and Zhongshan, which can be considered the main potential source areas. These areas can be regarded as the main potential source areas. The concentration weight trajectory showed that external and local sources affected the O3 pollution in Qingyuan during the four seasons. The high ozone concentration in Qingyuan mainly appeared in the south wind direction, indicating that the high ozone concentration in Qingyuan was greatly affected by the external transmission of the southern Pearl River Delta. The correlation between ozone concentration and CO concentration is poor, and the effect on ozone concentration is less than that of NO2.

[CT findings of ischemic infarction in relation to neuronal damage in rabbits].

OBJECTIVE: To explore the early changes in CT findings of ischemic infarction in relation to neuronal damage in rabbits. METHODS: Thirty-two rabbits were divided into control group and experiment groups and scanned with CT 2, 4, 8, 12, 18, 24, and 36 h after ischemic cerebral infarction induced by PVA embolization of the middle cerebral artery (MCA), respectively. The brain specimen were stained with HE, Nissle and TUNEL techniques for pathological examination. RESULTS: In stage I (2-8 h after MCA occlusion) by CT staging, the neurons exhibited ischemic change followed by cell edema. A small number of TUNEL-positive cells were found in the basal ganglia and cortex. In stage II (12-18 h after MCA occlusion), neuronal swelling and lysis were observed with greater number of TUNEL-positive neurons in the basal ganglia and cortex. In stage III ( 24-36 h after MCA obstruction), cerebral edema became obvious and ischemic cores were distinct, with numerous necrotic neurons seen and destruction of the cell structure. Numerous TUNEL-positive cells were seen in the ischemic penumbra and cortex. CONCLUSION: The damaged neurons after ischemic cerebral infarction showed varied morphology including cell edema, apoptosis, necrosis, and necrosis-apoptosis continuum. CT manifestations are strongly associated with the progression of ischemia and the pathological changes.

F3MB(PANDER) decreases mice hepatic triglyceride and is associated with decreased DGAT1 expression.

OBJECTIVE: Pancreatic-derived factor (PANDER, also named as FAM3B) is secreted by pancreatic α and ß cells. Increasing evidence suggests that it may serve a hormonal function related to glycemic and lipid metabolism. In this study, we investigated the effects of PANDER overexpression on hepatic and adipose triglyceride metabolism in high-fat diet-fed male C57BL/6 mice. METHODS: PANDER overexpression was achieved by tail-vein injection of recombinant Ad-PANDER and Ad-GFP injected mice served as a control. The TG metabolism in both groups were compared. RESULTS: Adenoviral-mediated overexpression of PANDER did not affect body weight, food consumption, or liver enzymes. The triglyceride (TG) content of both liver and adipose tissue was significantly decreased in Ad-PANDER mice (liver: 6.16±1.89 mg/g vs. control 14.95±2.27 mg/g, P<0.05; adipose: 39.31±1.99 mg/100mg vs. 47.22±2.21 mg/100mg, P<0.05). The free fatty acid (FFA) content of adipose tissue in Ad-PANDER mice was also decreased (1.38±0.18 mg/g vs. 2.77±0.31 mg/g, P<0.01). The investigation of key enzymes of triglyceride hydrolysis and FFA oxidation in liver and adipose tissue showed that p-HSL/HSL was significantly increased and that DGAT1 gene and protein expression were significantly reduced in the liver of PANDER-overexpressing mice. PKA phosphorylation was also significantly increased in the livers of Ad-PANDER mice. No differences in ATGL, CPT1, ACOX1, or DGAT2 expression were observed. CONCLUSION: Overexpression of PANDER is associated with observable decreases in TG, increases in PKA phosphorylation, and decreased DGAT1 expression, suggesting a possible interrelationship. The mechanisms by which this occurs remain to be elucidated.

[The value of three-phase pulmonary helical CT in diagnosing peripheral pulmonary cancer (diameter

OBJECTIVE: To evaluate the value of three-phase pulmonary helical CT in diagnosing peripheral pulmonary cancer (diameter

[Helical dual-phase CT scan in evaluating blood supply of primary heptocellular carcinoma after transcatheter hepatic artery chemoembolization with lipiodol].

OBJECTIVE: To evaluate the blood supply of low density viable area of primary heptocellular carcinoma after transcatheter hepatic artery chemoembolization using lipiodol (LP-TACE), by helical dual-phase CT scanning and three dimensional CT (3DCT). METHODS: Thirty-four patients with primary heptocellular carcinoma after LP-TACE were examined by hepatic helical dual-phase CT. 3DCT model of the maximum intensity projection (MIP), surface shaded display (SSD) reconstruction of the hepatic artery and portal vein were simultaneously done in 5 cases. RESULTS: Viable tumor areas of 34 cases of primary heptocellular carcinoma after LP-TACE were divided into four types: peripheral, lateral, central and diffused types. Enhanced tumor vessel or tissue in viable tumor area was found during hepatic dual-phase in 17 cases, during hepatic artery-phase only in 8 and hepatic portal vein-phase only in 3. The viable tumor areas were found to have blood supply from the hepatic vein in 2 cases. The viable tumor area unenhanced during hepatic dual-phase was found in 6 cases. In 5 cases, the relation between the viable tumor area and branches of hepatic artery and portal vein was showed by MIP and SSD of hepatic artery and portal vein. CONCLUSION: Hepatic helical dual-phase CT scan with 3DCT is effective in evaluating the blood supply of viable tumor areas and the therapeutic effect of primary heptocellular carcinoma after LP-TACE.

Influence of lesion ratio on diagnostic performance of in-phase/opposed-phase imaging and apparent diffusion coefficient for differentiating acute benign vertebral fractures and metastases.

BACKGROUND: The usefulness of in-phase/opposed-phase imaging and diffusion weighted imaging (DWI) in differentiating benign and neoplastic vertebral fractures has been described. In this study, we aimed to evaluate the influence of the severity of vertebral damage on the diagnostic performance of these two technologies. METHODS: Totally 59 patients with 68 acute benign vertebral fractures and 43 patients with 79 vertebral metastases were included in this study. The MR protocol included DWIs and sagittal in-phase/opposed-phase gradient recalled sequence. The severity of vertebral damage was expressed by lesion ratio (LR, the ratio of lesion area to vertebral area on the slices of largest abnormal signal area in the T1-weighted sequence). Quantitative (signal intensity ratio (SIR) defined as signal intensity (SI) on opposed-phase gradient recalled echo (GRE) images divided by SI on in-phase; apparent diffusion coefficient (ADC) value derived from DWI analysis was performed, the relationships between LR and the measurements of these two technologies were analyzed using linear regression. The covariate-specific receiver operating characteristic (ROC) curves were also fitted to evaluate the influence of LR on the diagnostic performance of ADC and SIR. RESULTS: The difference in both SIR and ADC for vertebral metastasis and acute benign vertebral fractures was significant (P < 0.001). A positive correlation between the LR and the SIR was found in benign fractures (P < 0.05). The severity of vertebral damage had a significant influence on the AUC (area under ROC curve) for SIR (P < 0.05) but ADC (P > 0.05). More severe cases were associated with increased AUC for SIR. CONCLUSIONS: LR is capable of affecting the diagnostic performances of chemical shift imaging. Thus, when applying these tests to make diagnoses on vertebral fractures, the severity of the vertebral damage should be taken into account. The covariate-specific ROC model is recommended because it substantially improves the ability to avoid bias when evaluating tests.

[Role of 16 slices spiral CT angiography with 3-dimensional CT and CT virtual endoscopy in detecting blood supply of lung carcinoma].

BACKGROUND & OBJECTIVE: Angiography, a common method in evaluating blood supply of lung carcinoma, is invasive and complicated, with low success rate for bronchial artery, and could not assure to show all supply blood vessels at a time. This study was to explore clinical value of 16 slices spiral CT angiography with 3-dimensional CT (3DCT) and CT virtual endoscopy (CTVE) in diagnosing and evaluating supply blood vessels and blood supply of lung carcinoma, so as to find a non-invasive, safe, simple and effective method in diagnosing blood supply of lung carcinoma. METHODS: A total of 72 patients with pathologically proved lung carcinoma underwent 16 slices spiral CT angiography with 3DCT. Volume rendering (VR), maximum intensity projection (MIP), and surface shaded display (SSD) of supply blood vessels of lung carcinoma were used as 3DCT models. CTVE of bronchial artery was performed in 25 patients. Color VR of tumor lesion was performed in all patients. RESULTS: Supply blood vessels were showed in 68 patients, 59 of them showed only bronchial artery, 5 showed intercostals arteries, and 4 showed mixed types, including bronchial artery, intercostals arteries, or branch arteries of subclavian artery. The bronchial artery entered into enlarged mediastinal lymph nodes in 4 patients. CTVE well displayed the orifice and lumen of bronchial arteries in the 25 patients. The extent of red color of tumor lesion on VR color image were divided into 4 types: no color (n=11), light red (n=17), moderate red (n=32), and heavy red (n=12); the added CT values of tumor lesion after enhanced CT were (6.16+/-2.23) Hu, (15.71+/-3.13) Hu, (25.47+/-2.71) Hu, and (44.31+/-19.68) Hu, respectively. The corresponding rate between enhanced type and distributive type of red color on color VR was 86.1%. CONCLUSIONS: The 16 slices spiral CT angiography with 3DCT and CTVE could show clearly supply blood vessels and blood supply of lung carcinoma. It is a non-invasive, simple and effective method in evaluating and diagnosing blood supply of lung carcinoma.