As an important member of the adisintegrin and metalloproteinase (ADAM) superfamily,ADAM17 can mediate a variety of membrane molecular hydrolysis off,such as adhesion molecules,cytokines,growth factors,etc,and play an important role in regulating tumor cell adhesion,apoptosis,metastasis and proliferation through the EGFR-PI3K-Akt pathway,Notch signaling pathway and other signaling pathways.The research of ADAM17 targeted drugs provides a new direction for cancer therapy.

Objective To evaluate the correlation of maternal FTO expression and insulin secretion levels in pregnant women.Methods In outpatient of Zhuhai Municipal Maternal and Child Healthcare Hospital,60 cases of pregnant women with gestational diabetes mellitus (GDM) and 60 cases of healthy pregnant women were recruited in this study from March 2016 to August 2016.Each pregnant woman was taken two tubes of venous blood.Lymphocytes was isolated from one tube of anticoagulated whole blood.The expression of FTO mRNA in lymphocytes was investigated using RT-PCR.Serum was isolated from another tube of non-anticoagulant whole blood.Its FTO protein was investigated using ELISA,insulin was investigated using chemiluminescence method,and GLU,CHO,TG,HDL-C and LDL-C were investigated by automatic biochemical analyzer.The correlation of the biochemical indicators were analyzed.Results The expression level of FTO mRNA,FTO protein,fasting glucose data,OGTT at 1 h and 2h glucose levels in the case group were 0.17 ％ ± 0.10 ％,61.32 ± 25.23 pg/ml,4.71 ±0.54 mmol/L,10.70±1.36 mmol/L and 8.97 ± 1.60 mmol/L respectively.The values of these biochemical indicators in control group were 0.11％±0.07％,51.47±22.97 pg/ml,4.41± 0.28 mmol/L,8.05±1.04 mmol/L and 6.56±0.75 mmol/L respectively.The differences were statistically significant (t =3.876,2.236,3.817,11.964 and 10.578,P＜0.05).The insulin levels were 6.83±9.76 mU/L in the case group,and 13.15±13.99 mU/L in control group.The differ ences was statistically significant too(t=-2.869,P＜0.05).FTO expression level was positively correlated with FTO protein,OGTT 1h glucose and OGTT 2h glucose levels (r=0.232,0.292,0.242,all P＜0.05),and it was negatively correlated with insulin levels(r=-0.185,P＜0.05).There was no correlation between FTO and fasting glucose expression levels (P ＞0.05).Conclusion The expression of FTO level in pregnant women with GDM was higher than that in healthy pregnant women.The relative expression of FTO mRNA was negatively correlated with insulin.And the regulation of glucose metabolism might be effected by insulin.

OBJECTIVETo estimate the feasibility of 16-multidetector spiral computed tomography (16-MDCT) on detecting coronary plaques in comparison with intravascular ultrasound (IVUS).

METHODSSixty-eight patients suspected of coronary heart diseases were examined by 16-MDCT, quantitative coronary angiography (QCA) and IVUS. Coronary stenosis was defined as lumen diameter reduction (DS) >or= 50%. Hounsfield units (HU) were used to determine different types of plaques: soft plaque (or= 120 HU).

RESULTSCompared to QCA, the sensitivity and the specificity for patients with DS >or= 50% were 91.8% (112/122) and 97.8% (556/568) respectively, the positive and negative predictive value were 90.3% (112/124) and 98.2% (556/566) respectively. In 96 plaques evaluated both by 16-MDCT and IVUS, 20 and 21 soft plaques, 37 and 36 fibrous plaques, 39 and 38 calcified plaques were identified by 16-MDCT and IVUS respectively. HU value of soft (11 +/- 36), fibrous (83 +/- 20), and calcified (292 +/- 80) plaques were significantly different (P < 0.05).

CONCLUSIONSNoninvasive 16-MDCT could correctly estimate coronary stenosis and coronary plaques compositions.

Aged ; Atherosclerosis ; diagnostic imaging ; Coronary Angiography ; Female ; Humans ; Male ; Middle Aged ; Tomography, Spiral Computed ; methods ; Ultrasonography, Interventional

Blood Platelets ; enzymology ; Diabetes Mellitus, Type 2 ; enzymology ; Enzyme Activation ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; pharmacology ; Nitric Oxide Synthase ; metabolism ; Nitric Oxide Synthase Type III ; Phosphorylation ; Pravastatin ; pharmacology ; Serine ; metabolism

In traditional Chinese medicine herbs (TCM), including Radix Salviae Miltiorrhizae (Danshen), Radix Puerariae Lobatae (Gegen), Radix Angelicae Sinensis (Danggui), and Rhizoma Chuanxiong (Chuanxiong) are widely used for the prevention and treatment of cardiovascular diseases and also often co-administered with Western drugs as a part of integrative medicine practice. Carboxylesterase 1 (CES1) plays a pivotal role in the metabolisms of pro-drugs. Since (S)-2-(2-(6-dimethylamino)-benzothiazole)-4,5-dihydro-thiazole-4-carboxylate (NLMe) has recently been identified by us as a selective CES1 bioluminescent sensor, we developed a rapid method using this substrate for the direct measurement of CES1 activity in rats. This bioluminescence assay was applied to determine CES1 activity in rat tissues after a two-week oral administration of each of the four herbs noted above. The results demonstrated the presence of CES1 enzyme in rat blood and all tested tissues with much higher enzyme activity in the blood, liver, kidney and heart than that in the small intestine, spleen, lung, pancreas, brain and stomach. In addition, the four herbs showed tissue-specific effects on rat CES1 expression. Based on the CES1 biodistribution and its changes after treatment in rats, the possibility that Danshen, Gegen and Danggui might alter CES1 ac-tivities in human blood and kidney should be considered. In summary, a selective and sensitive biolu-minescence assay was developed to rapidly evaluate CES1 activity and the effects of orally administered TCMs in rats.

Objective To explore the value of pepsinogen and endothelial function changes in patients with Helicobacter pylori(Hp)infection for the early evaluation of atrophic gastritis and gastric cancer.Methods A retrospective analysis was conducted on the clinical data of 163 patients with chronic gastritis complicated with Hp infection admitted from July 2022 to December 2023.Among them,78 patients with erosive gastritis complicated with Hp infection were in the Hp group,57 patients with chronic atrophic gastritis complicated with Hp infection were in the atrophic group,and 28 patients with gastric cancer complicated with Hp infection were in the gastric cancer group.The serum pepsinogen Ⅰ(PG Ⅰ),pepsinogen Ⅱ(PG Ⅱ)levels,and PG Ⅰ/PG Ⅱ ratio,as well as the levels of plasma nitrogen oxide(NO),endothelin-1(ET-1),intercellular adhesion molecule-1(ICAM-1)and other endothelial function indicators among the three groups of patients were compared,and Spearman correlation method was applied to analyze the relationship between the levels of pepsinogen and endothelial function indicators in patients with chronic gastritis complicated with Hp infection with the severity of their lesions.ROC curve was drawn to analyze the early evaluation value of pepsinogen and endothelial function indicators in patients with chronic gastritis and Hp infection for their progression to chronic atrophic gastritis or gastric cancer.Results Compared with those of the Hp group,the serum PG Ⅰ,PG Ⅰ/PG Ⅱ ratio,and plasma NO levels in the atrophic group and gastric cancer group decreased,while the plasma ET-1 and ICAM-1 levels in the atrophic group and gastric cancer group increased(P＜0.05);Compared with those of the atrophic group,the serum PG Ⅰ,PG Ⅰ/PG Ⅱ ratio,and plasma NO levels in the gastric cancer group decreased,while plasma ET-1 and ICAM-1 levels in the gastric cancer group increased(P＜0.05).There was no statistically significant difference in the levels of serum PG Ⅱ among the three groups(P＞0.05).The Spearman correlation analysis results showed that the serum PGⅠ,PG Ⅰ/PG Ⅱ ratio,and plasma NO level in patients with chronic gastritis complicated with Hp infection were negatively correlated with the severity of the disease(P＜0.05);The levels of plasma ET-1 and ICAM-1 were positively correlated with the severity of the lesion(P＜0.05).The ROC curve analysis results showed that serum PG Ⅰ,PG Ⅰ/PG Ⅱ ratio,and plasma NO,ET-1,and ICAM-1 levels all have certain early evaluation efficacy for the progression of chronic gastritis complicated with Hp infection to chronic atrophic gastritis or gastric cancer.Among them,the combined detection of various indicators had the best early evaluation efficacy.Conclusion Hp infection can lead to a decrease in pepsinogen levels and endothelial dysfunction in patients,and the combined detection of the levels of the two related indicators may serve as reference indicators for early risk assessment of Hp infection progression to chronic atrophic gastritis or gastric cancer.

OBJECTIVETo investigate whether p53 pathway participates in the effect of emodin on vascular smooth muscle cell proliferation.

METHODSThe effects of emodin on vascular smooth muscle cell proliferation were evaluated by cell count, senescent-associated beta-galactosidase staining, and annexin V staining. DNA synthesis was determined by (3)H-thymidine corporation, cell cycle was analyzed by FACS, the p53 protein level was measured by Western blot and cDNA expression array technology was used to demonstrate the effect of emodin on the simultaneous expression of a large number of genes in cultured vascular smooth muscle cells.

RESULTSEmodin at 1.6-3.1 microg/ml inhibited VSMC growth, at 6.3-12.5 microg/ml promoted VSMC aging and induced VSMC apoptosis at 25.0 microg/ml 24 hours after exposure. Unscheduled DNA synthesis, which was a sensitive indicator for DNA injury, was observed in VSMC following 24 hours emodin exposure. The mRNA and protein levels of p53 were up-regulated in a concentration-dependent manner. Proliferation/carcinogenesis-related genes were down-regulated and other genes related to cell senescence, apoptosis, and DNA damage/repair were up-regulated in VSMC after exposure to emodin for 24 hours. Emodin readily permeated VSMC membrane and mostly located in the cytoplasm and few of them in the nucleus.

CONCLUSIONSThe p53 pathway in VSMC was activated post emodin exposure in a concentration-dependent manner and which might be responsible for the observed antiproliferative effects of emodin in vascular smooth muscle cells.

Apoptosis ; drug effects ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; DNA Damage ; Emodin ; pharmacology ; Humans ; Myocytes, Smooth Muscle ; cytology ; drug effects ; metabolism ; RNA, Messenger ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

BACKGROUNDInvasive intravascular ultrasound (IVUS) is current diagnostic standard for myocardial bridging (MB). Non-invasive multislice computerized tomography coronary angiography (MSCT) technique has provided a good anatomical view of the tunnel artery now.

METHODSA total of 51 consecutive patients with atypical or typical angina scheduled for IVUS were enrolled in this study and MSCT was performed 7 days before IVUS. Coronary imaging was quantified using IVUS and MSCT. Four main vessels (left main artery (LMA), left anterior descending (LAD), left circumflex (LCX), right coronary artery (RCA)) were examined.

RESULTSForty-one out of 51 (80%) patients received metaprolol (25 mg) before the MSCT scan and 25 of them were current beta-blocker users. The mean heart rate was (64 +/- 3) beats per minute. A total of 51 patients underwent IVUS examination (30 with MB and 21 without MB) were chosen for this study. Twenty-eight out of 30 MB cases were correctly diagnosed by MSCT and 2 patients with MB were not detected. Comparison with IVUS, the sensitivity of detection by MSCT was 93%, specificity was 100%. The lumen diameter of the tunnel artery derived from MSCT and IVUS significantly decreased from (2.9 +/- 0.3) mm to (2.4 +/- 0.4) mm (P < 0.001) and from (3.3 +/- 0.3) mm to (2.6 +/- 0.5) mm (P < 0.001), respectively. Minimal and maximal diameters of MB derived from MSCT were significantly smaller than those from IVUS ((2.4 +/- 0.4) mm vs (2.6 +/- 0.5) mm, P < 0.05 and (2.9 +/- 0.3) mm vs (3.3 +/- 0.3) mm, P < 0.05), respectively.

CONCLUSIONSMSCT offers a reliable non-invasive method for MB in LAD and atherosclerosis diagnosis with diagnostic accuracy comparable with invasive IVUS.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Myocardial Bridging ; diagnostic imaging ; Tomography, Spiral Computed ; methods ; Ultrasonography, Interventional ; methods

BACKGROUNDTelocytes (TCs) are a novel type of interstitial cells, which have been recently described in a large variety of cavitary and noncavitary organs. TCs have small cell bodies, and remarkably thin, long, and moniliform prolongations called telopodes (Tps). Until now, TCs have been found in various loose connective tissues surrounding the arterioles, venules, and capillaries, but as a histological cellular component, whether TCs exist in large arteries remains unexplored.

METHODSTCs were identified by transmission electron microscope in the aortic arch of male C57BL/6 mice.

RESULTSTCs in aortic arch had small cell bodies (length: 6.06-13.02 μm; width: 1.05-4.25 μm) with characteristics of specific long (7.74-39.05 μm), thin, and moniliform Tps; TCs distributed in the whole connective tissue layer of tunica adventitia: TCs in the innermost layer of tunica adventitia, located at the juncture between media and adventitia, with their long axes oriented parallel to the outer elastic membrane; and TCs in outer layers of tunica adventitia, were embedded among transverse and longitudinal oriented collagen fibers, forming a highly complex three-dimensional meshwork. Moreover, desmosomes were observed, serving as pathways connecting neighboring Tps. In addition, vesicles shed from the surface of TCs into the extracellular matrix, participating in some biological processes.

CONCLUSIONSTCs in aorta arch are a newly recognized complement distinct from other interstitial cells in large arteries, such as fibroblasts. And further biologically functional correlations need to be elucidated.

Adventitia ; cytology ; Animals ; Aorta ; cytology ; Aorta, Thoracic ; cytology ; Cell Communication ; physiology ; Connective Tissue Cells ; cytology ; ultrastructure ; Male ; Mice ; Mice, Inbred C57BL ; Microscopy, Electron, Transmission

OBJECTIVETo explore the oxidative modification effect and its mechanism of low density lipoprotein (LDL) in hyperlipidemia (HL) rats after treating with tetrahydrobiopterin (BH4).

METHODSFifty four 8-week-old male Wistar rats were used, these 54 rats were randomly divided into control group, high fat diet group (HL group), high fat diet and injected BH4 group (HL + BH4 group), and 18 in each group. The BH4 levels of blood fats and blood serum and its metabolites, the aortic reactive oxygen species, the end product malondialdehyde (MDA) and the LDL oxidation level were all determined by killing 6 experimental rats in each group at the first 8, 16, and 24 weeks of age respectively.

RESULTSTreating with BH4 after 8 and 16 weeks, there was no significant difference in serum lipids among three groups (P > 0. 05); but ROS and MDA decreased significantly (P < 0.01); compared with control and HL groups, the BH4 level of HL + BH4 group increased a lot (P < 0.01); compared with control group, the BH4 content reduced obviously in aortic homogenate of HL group (P < 0.01), but the total petrin levels (TB = BH4 + BH2 + B) had no significant difference (P > 0.05); the serum TBARS formation increased gradually with the increase of week-ages, but compared with HL group, the serum TBARS formation of HL + BH4 group reduced significantly (P < 0. 01).

CONCLUSIONTreating with BH4 can reduced the LDL oxidation, the mechanism may be related to the correct of NOS uncoupling, the reduce of ROS generation and the decrease of LDL lipid peroxidation.

Animals ; Biopterin ; analogs & derivatives ; therapeutic use ; Hyperlipidemias ; blood ; drug therapy ; Lipid Peroxidation ; Lipids ; blood ; Lipoproteins, LDL ; metabolism ; Male ; Malondialdehyde ; metabolism ; Rats ; Rats, Wistar ; Reactive Oxygen Species ; metabolism