Primo Vascular System: An Endothelial-to-Mesenchymal Potential Transitional Tissue Involved in Gastric Cancer Metastasis.

Gastric cancer is the fourth commonest cancer in the world and the second leading cause of cancer-related death. Investigation of gastric cancer metastasis is one of the hottest and major focuses in cancer research. Growing evidence manifested that primo vascular system (PVS) is a new kind of circulatory system beyond vascular and lymphatic system. Previous researches revealed that PVS is a specific tissue between endothelium and mesenchyme and is involved in cancer, especially in tumor metastasis and regeneration. In current study, we investigated the role of primo vessels in gastric cancer metastasis and its possible relationship to vascular vessels formation. Our results indicated that primo vessels were involved in gastric cancer metastasis. We observed blood vessel-mediated metastasis, primo vessel-mediated metastasis, and an intermediate state between them. We deduced that primo vessels may be precursors of blood vessels. These results possibly provided a thoroughly new theoretic development in cancer metastasis.

Retinoic acid, testosterone or their combination affects the cell cycle of adipose-derived stem cells / 中国组织工程研究

BACKGROUND:The researches about the effect of retinoic acid on the proliferation of adipose-derived stem cells are rare, and the researches on the testosterone are mainly on the inhibition of cellaging. OBJECTIVE: To study the effects of retinoic acid and testosterone or combination on the cellcycle of adipose derived stem cells. METHODS:Adipose derived stem cells were isolated from adult female Sprague Dawley rats with 2 months age and cultured in vitro til passage 3 adipose derived stem cells, and then the 3rd passage adipose-derived stem cells were performed with adipogenic induction, osteogenic induction and surface marker identification. The cells were divided into six groups:(1) Control group;(2) 10-5 mol/L retinoic acid group;(3) Retinoic acid group;(4) 10-5 mol/L retinoic acid+testosterone group;(5) 10-6 mol/L retinoic acid+testosterone group;(6) Testosterone group. The adipose-derived stem cells in the control group were cultured with Dulbecco’s modified Eagle’s medium+10%fetal bovine serum culture medium, and the adipose-derived stem cells in the other five groups were induced with corresponding dose of retinoic acid and testosterone on the basis of control group. After cultured for 36 hours, the flow cytometry was used to detect the changes of cellcycle. RESULTS AND CONCLUSION:Compared with the control group, cellproportions in phase G 1 of 10-5 mol/L retinoic acid group and 10-6 mol/L retinoic acid group were increased significantly, and the cellproportions in phase S were decreased. Compared with control group, the cellproportion in phase G 1 of testosterone group was significantly reduced, and the cellproportion in phase S was increased. Compared with 10-5 mol/L retinoic acid group and 10-6 mol/L retinoic acid group, cellproportions in phase G 1 of 10-5 mol/L retinoic acid+testosterone group and 10-6 mol/L retinoic acid+testosterone group were reduced significantly and the cellproportions in phase S were increased. Retinoic acid can inhibit the cellcycle of adipose-derived stem cells in phase G 1 , and delay the process of the cellcycle from phase G1 to phase S;while testosterone can promote the cellcycle of adipose-derived stem cells from phase G1 to phase S;the combination induction of retinoic acid and testosterone can accelerate the process of the cellcycle of adipose-derived stem cells from phase G 1 to phase S.

Discovery of endothelium and mesenchymal properties of primo vessels in the mesentery.

Recent evidences demonstrated that endothelial-to-mesenchymal transition (EndMT) has a crucial role in cancer and is recognized as a unique source of cancer-associated fibroblasts (CAFs). Primo vascular system (PVS) is a new circulatory system which may play an important role in cancer metastasis and regeneration. In the current study, we applied previously established time-saving method to identify primo vessels and further investigated the immunocytochemical properties of primo vessels. Both primo vessels and primary primo vessel cells in the mesentery expressed endothelial markers and fibroblast markers. Double-labeling experiments demonstrated that endothelial and fibroblast markers are coexpressed in primo vessels. In addition, under the stimulation of TGF-ß1 in vitro, primary primo vessel cells differentiated into fibroblasts. Therefore, we found that primo vessels in the mesentery had a transitional structure between endothelium and mesenchymal. This is a new finding of EndMT in normal postnatal animals.

Ca²âº/calmodulin-dependent protein kinase II mediates platelet-derived growth factor-induced human hepatic stellate cell proliferation.

BACKGROUND AND AIM: Proliferation and activation of myofibroblastic hepatic stellate cells (HSCs) in response to growth factors is essential for the development of liver fibrosis. As one of the most potent factors, platelet-derived growth factor (PDGF) activates intracellular signals and contributes to sustained HSCs activation. Growing evidence has suggested that the Ca(2+) signal is involved in PDGF pathways. We showed previously for the first time that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is essential for human HSC proliferation. The inhibition of CaMKII by its specific inhibitor, KN-93, significantly decreased the HSC growth and increased expression of cell cycle suppressive regulators P53 and P21. METHODS: In the present study, we investigated the role of CaMKII in PDGF-induced HSC proliferation and underlying mechanisms. RESULTS: We confirmed that in human HSCs, PDGF significantly increased CaMKII mRNA levels, protein expression, and phosphorylation. The interruption of CaMKII by KN-93, specific inhibitory peptide (AIP), or specific CaMKII knockdown by its siRNA not only attenuated PDGF-induced HSC proliferation but also ERK1/2 phosphorylation. However, CaMKII had no effect on JNK phosphorylation. In addition, inhibitors of ERK1/2 (PD98059) and JNK (SP600125) did not affect CaMKII expression. Interruption of CaMKII-ERK cascade, not JNK signal, inhibited PDGF-induced HSC proliferation. CONCLUSION: We confirmed that CaMKII mediated PDGF-induced human HSC proliferation through ERK1/2 but not the JNK mechanism. Our study shed light on CaMKII as a crucial signal in PDGF-activated HSCs and a potential therapeutic point in hepatic fibrosis.

Effect of retinoic acid on alkaline phosphatase expression in rat adipose-derived stem cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate whether adipose-derived stem cells (ADSCs) induced by retinoic acid (RA) in vitro express primordial germ cell marker alkaline phosphatase (ALP) and vasa.</p><p><b>METHODS</b>ADSCs were isolated from adult female SD rats and cultured in vitro. The third passage of ADSCs was identified by adipogenic differentiation, osteogenic differentiation and cell surface marker detection. The ADSCs were treated with 1×10(-5), 1×10(-6), or 1×10(-7) mol/L RA for 7 or 14 days, and the cellular expression of ALP was detected. vasa mRNA expression in ADSCs treated with 1×10(-5) mol/L RA for 7 days was detected using RT-PCR.</p><p><b>RESULTS</b>The OD value of ADSCs treated with 1×10(-5), 1×10(-6), or 1×10(-7) mol/L RA was 0.59∓0.04, 0.27∓0.07, and 0.15∓0.03 after a 7-day treatment, and was 0.42∓0.02, 0.34∓0.01, and 0.19∓0.02 after a 14-day treatment, respectively, demonstrating significantly enhanced ALP expression in RA-treated ADSCs compared with that in the control cells (0.07∓0.01 and 0.07∓0.01 at 7 and 14 days, respectively, P<0.01). The ADSCs showed a negative vasa mRNA expression after 1×10(-5) mol/L RA treatment for 7 days.</p><p><b>CONCLUSION</b>RA-induced ADSCs express ALP, a marker of primordial germ cells, but does not express the primordial germ cell marker vasa.</p>

Roux-en-Y gastric bypass improves carbohydrate and lipid metabolism in nonfat type 2 diabetes mellitus patients / 中华普通外科杂志

Objective To evaluate Roux-en-Y gastric bypass operation on carbohydrate and lipid metabolism in type 2 diabetes mellitus patients with BMI range of 24 -29. Methods Thirty seven cases of type 2 diabetes mellitus patients undergoing Roux-en-Y gastric bypass operation were studied. Body mass index (BMI), glycosylated hemoglobin ( GHbAlc), fasting glucose ( FPG), fasting insulin (FIns) and C-peptide( FC-p), HOMA-IR, oral glucose tolerance (OGTT) including 2 hour insulin (2hIns) and C-peptide (2hC-p) , plasma levels of total cholesterol (TC), triglycerides(TG), high density lipoprotein( HDL-c)and low density lipoprotein ( LDL-c) were measured preoperatively and on 3 months, 6 months, later postoperatively. Result There was no statistically significant difference between BMI values measured preoperatively and postoperatively (P>0. 05 ). Serum levels measured in pre-operative and third and sixth post-operative months were: FPG (8. 8 ± 0. 9, 7. 0 ± 2. 0, 6. 3 ± 0. 6, P<0. 01) ( mmol/L) , GHbAlc (8.2±1.2, 7.0±0.8, 6.2±0.7, P<0.01)(%), FIns(10. 6 ±1. 2, 9.0±0.9, 9.0±0.8, P<0.05)(mU/L), FC-p(1.9±0.5, 1.2 ±0.6, 1.2 ±0.4, P<0. 01) (nmol/L), TG(3.3 ±0.8, 2.7 ±0.9,2.6±0.7, P<0.05)(mmol/L), TC(6.5±1.8, 4.6±0.9, 4.2 + 1.0, P<0. 05) (mmol/L)and LDL-c (3. 6 ±1.2, 2. 8 ±0.8, 2. 7 ±0.2, P<0.01) (mmol/L), 2 hour glucose after OGTT(2hPG) (18. 6 ±3.0, 12.7 ±2.3, 11.4±2.0, P<0. 01) (mmol/L), HOMA-IR(3. 2 ± 1. 7, 2.6±1.6, 2. 5 ±1.3, P<0. 05). Postoperative levels of HDL-c (1. 2 ± 0. 1, 1. 4 ± 0. 4, 1. 4 ± 0. 2, P<0. 01) ( mmol/L) , 2hIns (17. 2 ±3.4, 26. 3 ±4.7, 28. 6 ±4.1, P<0. 01) (mU/L)and 2hC-p(4. 2 ± 1. 0, 6. 3 ± 1. 5, 6. 2 ± 1.4,P<0. 01 ) ( nmol/L) were significantly higher than that of the pre-operative values ( P<0. 01 ).Conclusions Roux-en-Y gastric bypass significantly improves the metabolism of carbohydrate and lipid in type 2 diabetes patients with BMI 24-29, and the effects are not associated with weight loss.

Effects of gastric bypass on carbohydrate and lipid metabolism in non-obese patients with type 2 diabetes and gastric carcinoma / 中华普通外科杂志

Objective To observe the effects of Roux-en-Y gastrointestinal reconstruction(RYGR) on carbohydrate and lipid metabolism in non-obese patients with type 2 diabetes and gastric carcinoma.Methods Fifty seven gastric cancer cases who underwent radical distal gastrectomy were studied and among them 35 patients had Roux-en-Y gastrointestinal reconstruction (RYGR group) and 22 had Billroth-Ⅰ gastrointestinal reconstruction (B-I GR group).Both groups were subjected to the measuring of preoperative and postoperative third,sixth months values of body mass index (BMI),glycosylated hemoglobin (GHbA1c),fasting glucose (FPG),fasting insulin (Flns) and C-peptide (FC-P),oral glucose tolerance (OGTT) including 2 hour insulin (2hIns) and C-peptide (2hC-P),plasma levels of total cholesterol (TC),triglycerides (TG),high density lipoprutein (HDL-c) and low density lipoprotein (LDL-c).Result There was no significant difference between the two groups in preoperative values (P＞0.05).There was no statistically significant difference in BMI values measured postoperatively (P ＞ 0.05).In RYGR group,preoperative FPG and that of third and sixth month postoperatively was (9.3±0.9) mmol/L vs.(7.2±2.1) mmol/L vs.(7.1±0.8) mmol/L,P=0.000,GHbAlc was (9.2±1.2)% vs.(7.3±1.2)% vs.(7.2±1.1)%,P=0.000,TG was (3.21±0.88) mmol/L vs.(2.12±0.97) mmol/L vs.(2.02±0.09) mmol/L,P =0.000,TC was (6.4±1.9) mmol/L vs.(4.3±1.0) mmol/L vs.(4.1±1.0) mmol/L,P =0.000 and LDL-c was (3.61±1.05) mmol/L vs.(2.77±0.68) mmol/L vs.(2.71±0.18)mmool/L,P=0.000,2 hour glucose after OGTT(2hPG) was (17.6±2.5) mmol/L vs.(12.1±1.9) mmol/L vs.(11.6±2.3) mmol/L,P = 0.000.Levels of FIns was (98±11) pmol/L vs.(120±9)pmol/L vs.(122±8) pmol/L,P =0.000,FC-P was (0.21±0.08) mmol/L vs.(0.30±0.01) mmol/L vs.(0.30±0.01) mmol/L,P=0.000,HDL-c was (1.08±0.10) mmol/L vs.(1.61±0.34) mmol/L vs.(1.62±0.09) mmol/L,P = 0.000,2 h Ins was (410±19) pmol/L vs.(446±19) pmol/L vs.(459±18) pmol/L,P = 0.000 and 2 h C-P was (0.87±0.17) mmol/L vs.(1.22±0.14) mmol/L vs.(1.19±0.15) mmol/L,P =0.000.In B-I GR group,preoperative and third and sixth postoperative month values of GHbA1c were (9.2±1.2)% vs.(8.4±1.6)% vs.(8.3±1.1)%,P =0.046.Conclusion Roux-en-Y gastric bypass can significantly improve the metabolism of carbohydrate and lipid in non-obese patients with type 2 diabetes and gastric carcinoma,and the effects are not related with postoperative weight loss.

Anti-aging effect of allografting adipose-derived stem cells in rats / 解剖学报

Objective To observe the effect of transplanting the adipose-dervived stem cells(ADSCs) on free radical metabolism and immune function of rat aging model induced by D-galactose from fasiaology perspective;to explore a new method for anti-aging. Methods The ADSCs were cultured in vitro. Thirty male SD rats were randomly divided into 3 groups: normal control group(A), aging model group(B) and treat group(C). Ten rats in each group. Rats in B and C groups were injected D-galactose continually into make the sub-acute aging model rats.After 8-week injections of D-galactose;R3ats in group C were injected ADSCs(3×10~6/ml) through caudal vein. After 2-week transplantions of ADSCs, T-SOD, CuZn-SOD, MDA, NO, IL-2 and spleen index levels in serums of each group were detected and compared among the three groups. Results Compared with the A group, the SOD, NO, IL-2 level and spleen index in serum in group B decreased significantly, while the contents of MDA increased significantly. Compared with group B, the SOD, NO, IL-2 level and spleen index in serum in group C had been improved, and the contents of MDA decreased significantly. Conclusion Transplanting ADSCs can improve the antioxidant ability and strengthen the cellular immune function of aging rats.Further more, it can delay the ageing procedure induced by D-galactose in rats.

Mechanical and physicochemical properties of xenogeneic bone scaffold materials A comparative study / 中国组织工程研究

BACKGROUND: The core of bone tissue engineering is to construct a scaffold that is similar to human bone tissue structure and features.OBJECTIVE: To compare pathochemical and mechanical characteristics between pig and human bone scaffold materials.DESIGN, TIME AND SETTING: Contrast study was performed at Clinical Anatomy Institute, South Medical University; Guangdong Province Key Laboratory of Tissue Construction and Detection from March to December 2006.MATERIALS: Four fresh health adult human cadavers were provided by South Medical University, Guangzhou Red Cross Society, and the relatives knew the fact. Ultra low temperature freezing 6-month iliac bones of 6 adult swines were also used in this study.METHODS: Pig iliac and healthy adults iliac bones were obtained to remove soft tissue, curettage periosteum and bone marrow. Bone sawing machine was used to cut cancellous bone into smaller bone sections around 5 mm×5 mm×40 mm, which underwent ultrasonic cleaning, H2O2 and alcohol soaking, freeze drying and radiation treatment; finally, xenogeneic bone scaffold and allogeneic bone scaffold were obtained.MAIN OUTCOME MEASURES: Xenogeneic bone scaffold material and human allograft bone scaffold were observed with scanning electron microscopy to compare porosity, contents of protein content, calcium and phosphorus, and mechanical properties.RESULTS: Xenogeneic bone scaffold and allogeneic bone scaffold both had intrinsical bone trabecula, trabecular spaces and bone cavity system. Both of them had unabridged natural three dimensional network structure. The 3D supporting frames of them were complete. The xenogeneic bone scaffold had more spaces than allogeneic bone scaffold. The size of both scaffolds was approximation, about 400 μm. The interval porosity of xenogeneic bone scaffold was higher than the allogeneic bone scaffold (P<0.05). And the protein of xenogeneic bone scaffold was not as many as it of allogeneic bone scaffold (P<0.05). The contents of Ca and P were similar (P>0.05), and there was no significant difference in Young's modulus of xenogeneic bone scaffold and allogeneic bone scaffold (P>0.05).CONCLUSION: Xenogeneic bone scaffold may completely meet the clinical demands for bone grafting or be the scaffold of bone tissue engineering in mechanical chemical properties.

Applied anatomy and cast observation in lingual arterial chemoembolization / 实用口腔医学杂志

Objective: To provide anatomical basis for the chemotherapy of lingual arterial embolization in clinic. Methods: The origin, course, branch distribution and anastomosis of the lingual artery were observed in 15 cases of adult head specimens. Results: As one of principal branches, the lingual artery arises from the external carotid artery at the level of the major cornu of hyoeides, approaches to the carotid bifurcation. With original diameter of (2.4?0.3) mm, it runs upward and passes deepwards to the hyoglossus muscle, gives off the dorsal lingual artery and the terminal branch -profunda lingual artery. Limited in each side of intrinsic muscles, two profunda lingual arteries creep tortuously along the muscular fibers and anastomose freely to structure submucous arterial rete. Conclusion: With concentrated origins, wide vascular diameter, constant course and enrichment of submucous arterial rete, the lingual artery is an ideal blood vessel for arterial chemoembolization.