AIM: To explore the expression of reversion inducing cysteine-rich protein with Kazal motifs (RECK), vascular endothelial growth factor (VEGF) and endoglin (CD105) protein and its correlation with occurrence, developm...AIM: To explore the expression of reversion inducing cysteine-rich protein with Kazal motifs (RECK), vascular endothelial growth factor (VEGF) and endoglin (CD105) protein and its correlation with occurrence, development, invasion and metastasis in esophageal squamous cell carcinoma (ESCC). METHODS: Streptavidin-peroxidase (SP) immunohisto- chemistry was used to detect expression of RECK and VEGF in 62 cases of ESCC, 31 cases of adjacent atypical hyperplastic epithelium and 62 cases of normal esophageal epithelium. CD105 Mb was used to assess microvessel density (MVD). RESULTS: The expression of RECK was closely correlated with histological grade, infiltrative depth and lymphatic metastasis in ESCC (P < 0.05). The expression of RECK decreased during cancer development: normal esophageal epithelium (85.5%, 53/62), adjacent atypical hyperplastic epithelium (71.0%, 22/31), and carcinoma (59.7%, 37/62). There was a significant difference among the groups (P < 0.05). The expression of VEGF protein was closely correlated with infiltrative depth and lymphatic metastasis in ESCC (P < 0.05). The expression of VEGF protein increased during cancer development: normal esophageal epithelium (29.0%, 18/62), adjacent atypical hyperplastic epithelium (54.8%, 17/31), and carcinoma (67.7%, 42/62). There was a significant difference among the groups (P < 0.05). MVDCD105 increased in accordance with histological grade, butthere was no significant difference (grade Ⅰ, 36.92 ± 10.85; grade Ⅱ, 37.65 ± 9.50; and grade Ⅲ, 38.06 ± 12.19). The MVDCD105 was closely correlated with infiltration and lymphatic metastasis in ESCC (P < 0.05). The expression of RECK was inversely correlated with the expression of VEGF and CD105. CONCLUSION: RECK, VEGF and CD105 play important roles in the infiltration, metastasis and carcinogenesis in esophageal carcinoma. Angiogenesis in ESCC may be promoted by over-expression of CD105.展开更多
Percutaneous microballoon compression of the trigeminal ganglion is a brand new operative technique for the treatment of trigeminal neuralgia. However, it is unclear how the procedure mediates pain relief, and there a...Percutaneous microballoon compression of the trigeminal ganglion is a brand new operative technique for the treatment of trigeminal neuralgia. However, it is unclear how the procedure mediates pain relief, and there are no standardized criteria, such as compression pressure, com- pression time or balloon shape, for the procedure. In this study, percutaneous microballoon compression was performed on the rabbit trigeminal ganglion at a mean inflation pressure of 1,005 ＋ 150 mmHg for 2 or 5 minutes. At 1, 7 and 14 days after percutaneous microballoon compression, the large-diameter myelinated nerves displayed axonal swelling, rupture and demy- elination under the electron microscope. Fragmentation of myelin and formation of digestion chambers were more evident after 5 minutes of compression. Image analyzer results showed that the diameter of trigeminal ganglion cells remained unaltered after compression. These experi- mental findings indicate that a 2-minute period of compression can suppress pain transduction. Immunohistochemical staining revealed that vascular endothelial growth factor expression in the ganglion cells and axons was significantly increased 7 days after trigeminal ganglion compression, however, the changes were similar after 2-minute compression and 5-minute compression. The upregulated expression of vascular endothelial growth factor in the ganglion cells after percu- taneous microballoon compression can promote the repair of the injured nerve. These findings suggest that long-term compression is ideal for patients with recurrent trigeminal neuralgia.展开更多
Background Sterol regulatory element binding protein （SREBP）-2 plays a key role in lipid homeostasis by stimulating gene expression of cholesterol biosynthetic pathways. The insulin-like growth factor binding prote...Background Sterol regulatory element binding protein （SREBP）-2 plays a key role in lipid homeostasis by stimulating gene expression of cholesterol biosynthetic pathways. The insulin-like growth factor binding protein （IGFBP） family regulates growth and metabolism, especially bone cell metabolism, and correlates with osteonecrosis. However, association of their gene polymorphisms with risk of avascular necrosis of the femoral head （ANFH） has rarely been reported. We determined whether SREBP-2 and IGFBP-3 gene polymorphisms were associated with increased ANFH risk in the Chinese population. Methods Two single nucleotide polymorphisms of SREBP2 gene, rs2267439 and rs2267443, and one of IGFBP-3 gene, rs2453839, were selected and genotyped in 49 ANFH patients and 42 control individuals by direct sequencing assay. Results The frequencies of rs2267439 TT and rs2267443 GA of SREBP2 and rs2453839 TT and CT of IGFBP-3 in the ANFH group showed increased and decreased tendencies （against normal control group）, respectively. Interaction analysis of genes revealed that the frequency of carrying rs2267439 TT and rs2267443 GA genotypes of SREBF-2 in ANFH patients was significantly higher than in the control group （P 〈0.05）. Association analysis between polymorphisms and clinical phenotype demonstrated that the disease course in ANFH patients with the rs2453839 TT genotype of IGFBP-3 was significantly shorter than that of CT＋CC carriers （P 〈0.01）. CT＋CC genotype frequency in patients with stage Ill/IV bilateral hip lesions was significantly higher than in those with stage Ill/IV unilateral lesions and stage II/111 bilateral lesions （P 〈0.05-0.02）. Conclusions Our results suggested that interaction of SREBP-2 gene polymorphisms and the relationship between the polymorphisms and clinical phenotype of IGFBP-3 were closely related to increased ANFH risk in the Chinese population. The most significant finding was that the CT＋CC genotype carriers of IGFBP-3 rs2453839 were highly associated with t展开更多
Neuroprotection by ischemic preconditioning has been confirmed by many studies, but the precise mechanism remains unclear. In the present study, we performed cerebral ischemic pre- conditioning in rats by simulating a...Neuroprotection by ischemic preconditioning has been confirmed by many studies, but the precise mechanism remains unclear. In the present study, we performed cerebral ischemic pre- conditioning in rats by simulating a transient ischemic attack twice （each a 20-minute occlusion of the middle cerebral artery） before inducing focal cerebral infarction （2 hour occlusion-reper- fusion in the same artery）. We also explored the mechanism underlying the neuroprotective effect of ischemic preconditioning. Seven days after ocdusion-reperfusion, tetrazolium chloride staining and immunohistochemistry revealed that the infarct volume was significantly smaller in the group that underwent preconditioning than in the model group. Furthermore, vascular endothelial growth factor immunoreactivity was considerably greater in the hippocampal CA3 region of preconditioned rats than model rats. Our results suggest that the protective effects of ischemic preconditioning on focal cerebral infarction are associated with upregulation of vascu- lar endothelial growth factor.展开更多
AIM: To improve osteogenic differentiation and attachment of cells.METHODS: An electronic search was conducted inPub Med from January 2004 to December 2013. Studies which performed smart modifications on conventional ...AIM: To improve osteogenic differentiation and attachment of cells.METHODS: An electronic search was conducted inPub Med from January 2004 to December 2013. Studies which performed smart modifications on conventional bone scaffold materials were included. Scaffolds with controlled release or encapsulation of bioactive molecules were not included. Experiments which did not investigate response of cells toward the scaffold(cell attachment, proliferation or osteoblastic differentiation) were excluded. RESULTS: Among 1458 studies, 38 met the inclusion and exclusion criteria. The main scaffold varied extensively among the included studies. Smart modifications included addition of growth factors(group Ⅰ-11 studies), extracellular matrix-like molecules(group Ⅱ-13 studies) and nanoparticles(nano-HA)(group Ⅲ-17 studies). In all groups, surface coating was the most commonly applied approach for smart modification of scaffolds. In group I, bone morphogenetic proteins were mainly used as growth factor stabilized on polycaprolactone(PCL). In group Ⅱ, collagen 1 in combination with PCL, hydroxyapatite(HA) and tricalcium phosphate were the most frequent scaffolds used. In the third group, nano-HA with PCL and chitosan were used the most. As variable methods were used, a thorough and comprehensible compare between the results and approaches was unattainable.CONCLUSION: Regarding the variability in methodology of these in vitro studies it was demonstrated that smart modification of scaffolds can improve tissue properties.展开更多
Müller cells are macroglia and play many essential roles as supporting cells in the retina.To respond to pathological changes in diabetic retinopathy(DR),a major complication in the eye of diabetic patients,retin...Müller cells are macroglia and play many essential roles as supporting cells in the retina.To respond to pathological changes in diabetic retinopathy(DR),a major complication in the eye of diabetic patients,retinal Müller glia produce a high level of vascular endothelial growth factor(VEGF or VEGF-A).As VEGF is expressed by multiple retinal cell-types and Müller glia comprise only a small portion of cells in the retina,it has been a great challenge to reveal the function of VEGF or other globally expressed proteins produced by Müller cells.With the development of conditional gene targeting tools,it is now possible to dissect the function of Müller cell-derived VEGF in vivo.By using conditional gene targeting approach,we demonstrate that Müller glia are a major source of retinal VEGF in diabetic mice and Müller cell-derived VEGF plays a significant role in the alteration of protein expression and peroxynitration,which leads to retinal inflammation,neovascularization,vascular leakage,and vascular lesion,key pathological changes in DR.Therefore,Müller glia are a potential cellular target for the treatment of DR,a leading cause of blindness.展开更多
Nerve growth factor（NGF） plays an important role in promoting neuroregeneration after peripheral nerve injury. However, its effects are limited by its short half-life; it is therefore important to identify an effect...Nerve growth factor（NGF） plays an important role in promoting neuroregeneration after peripheral nerve injury. However, its effects are limited by its short half-life; it is therefore important to identify an effective mode of administration. High-frequency ultrasound（HFU） is increasingly used in the clinic for high-resolution visualization of tissues, and has been proposed as a method for identifying and evaluating peripheral nerve damage after injury. In addition, HFU is widely used for guiding needle placement when administering drugs to a specific site. We hypothesized that HFU guiding would optimize the neuroprotective effects of NGF on sciatic nerve injury in the rabbit. We performed behavioral, ultrasound, electrophysiological, histological, and immunohistochemical evaluation of HFU-guided NGF injections administered immediately after injury, or 14 days later, and compared this mode of administration with intramuscular NGF injections. Across all assessments, HFU-guided NGF injections gave consistently better outcomes than intramuscular NGF injections administered immediately or 14 days after injury, with immediate treatment also yielding better structural and functional results than when the treatment was delayed by 14 days. Our findings indicate that NGF should be administered as early as possible after peripheral nerve injury, and highlight the striking neuroprotective effects of HFU-guided NGF injections on peripheral nerve injury compared with intramuscular administration.展开更多
AIM： To investigate the effects of experimental partial hepatectomy and normothermic ischemia-reperfusion damage on the time course of the expression of four different growth factor receptors in liver regeneration. T...AIM： To investigate the effects of experimental partial hepatectomy and normothermic ischemia-reperfusion damage on the time course of the expression of four different growth factor receptors in liver regeneration. This is relevant due to the potential therapeutic use of growth factors in stimulating liver regeneration. METHODS： For partial hepatectomy （PH） 80% of the liver mass was resected in Sprague Dawley rats. Ischemia and reperfusion （I/R） were induced by occlusion of the portal vein and the hepatic artery for 15 min. The epidermal growth factor receptor, hepatic growth factor receptor, fibroblast growth factor receptor and tumour necrosis factor receptor-1 were analysed by immunohistochemistry up to 72 h after injury. Quantitative RT-PCR was performed at the time point of minimal receptor expression （24 h）. RESULTS： In immunohistochemistry, EGFR, HGFR, FGFR and TNFR1 showed biphasic kinetics after partial hepatectomy with a peak up to 12 h, a nadir after 24 h and another weak increase up to 72 h. During liver regeneration, after ischemia and reperfusion, the receptor expression was lower; the nadir at 24 h after reperfusion was the same. To evaluate whether this nadir was caused by a lack of mRNA transcription, or due to a posttranslational regulation, RT-PCR was performed at 24 h and compared to resting liver. In every probe there was specific mRNA for the receptors. EGFR, FGFR and TNFR1 mRNA expression was equal or lower than in resting liver, HGFR expression after I/R was stronger than in the control. CONCLUSION： At least partially due to a post-transcriptional process, there is a nadir in the expression of the analysed receptors 24 h after liver injury. Therefore, a therapeutic use of growth factors to stimulate liverregeneration 24 h after the damage might be not successful.展开更多
AIM： To study the protective effect of non-mitogenic human acidic fibroblast growth factor （FGF） on cardiac oxidative injury in vivo. METHODS： Ventricular cardiomyocytes were isolated from 1- to 3-d-old neonatal S...AIM： To study the protective effect of non-mitogenic human acidic fibroblast growth factor （FGF） on cardiac oxidative injury in vivo. METHODS： Ventricular cardiomyocytes were isolated from 1- to 3-d-old neonatal SD mice and cultured in Dulbecco＇s minimum essential medium supplemented with 15% fetal bovine serum under an atmosphere of 50 mL/L CO2-95% air at 37℃, as well as assessed by immunooltochemical assay. We constructed the cardiomyoolte injury model by exposure to a certain concentration of H2O2. Cellular viability, superoxide dismutase （SOD） activity, leakage of maleic dialdehyde and anti-apoptosis effect were included to evaluate the cardiac protective effect of non-mitogenic human acidic FGF. RESULTS： Over 50% of the cardiomyocytes beat spontaneously on the 2nd d of culture and synchronously beat after being cultured for 3 d. Forty-eight hours after plating was completed, the purity of such cultures was 95% myocytes, assessed by an immunocytochemical assay. Cellular viability dramatically decreased with the increasing of the concentration of H2O2. Non-mitogenic human acidic FGF showed significant resistance to thetoxic effect of H2O2, significantly increased the cellular viability as well as the activity of SOD, and dramatically decreased the leakage of maleic dialdehyde as well as the cellular apoptosis rate. CONCLUSION： Hydrogen peroxide shows strong cytotoxicity to the cultured cardiac myocytes, and non-mitogenic human acidic FGF shows strong cardio-protective effect when exposed to a certain concentration of H2O2.展开更多
OBJECTIVE: To investigate the neural differentiation capacity of water extraction of velvet antler.METHODS: Velvet antler(Cervus Nippon Temminck) polypeptide(VAP) was used to differentiate neural stem cells(NSCs) towa...OBJECTIVE: To investigate the neural differentiation capacity of water extraction of velvet antler.METHODS: Velvet antler(Cervus Nippon Temminck) polypeptide(VAP) was used to differentiate neural stem cells(NSCs) towards neurons in the study. Firstly, we obtain the polypeptides of VAP by water extraction. Secondly, we observed the morphology, assayed the factors in the media by enzyme-linked immunosorbent assay, and detected the special neural molecules by immuno fl uorescence staining. NSCs were cultured on the cell climbing film. After neuronal differentiation, differentiated NSCs were mounted for immunocytochemistry with immunofluorescence technique.RESULTS: The differentiating cells look like neuron,some special factors, such as Glial cell line-derived neurotrophic factor, nerve growth factor, in the media can be detected while differentiated neuron-like cells can express the special neural molecules.CONCLUSION: Differentiation of NSCs towards neurons can be induced by velvet antler polypeptide.展开更多
AIM： To investigate the angiogenesis-related protein expression profile characterizing metastatic colorectal cancer （mCRC） with the aim of identifying prognostic markers.METHODS： The expression of 44 angiogenesis-...AIM： To investigate the angiogenesis-related protein expression profile characterizing metastatic colorectal cancer （mCRC） with the aim of identifying prognostic markers.METHODS： The expression of 44 angiogenesis- secreted factors was measured by a novel cytokine antibody array methodology. The study evaluated vas- cular endothelial growth factor （VEGF） and its soluble vascular endothelial growth factor receptor （sVEGFR）-I protein levels by enzyme immunoassay （EIA） in a panel of 16 CRC cell lines, mRNA VEGF and VEGF-A isoforms were quantified by quantitative reverse-transcription polymerase chain reaction （Q-RT-PCR） and vascular en- dothelial growth factor receptor （VEGFR）-2 expressionwas analyzed by flow cytometry.展开更多
Background： Angiogenesis is the formation of new blood vessels to supply nutrients to tumors. Vascular endothelial growth factor （VEGF） and cluster of differentiation 34 （CD34） are important signaling proteins in...Background： Angiogenesis is the formation of new blood vessels to supply nutrients to tumors. Vascular endothelial growth factor （VEGF） and cluster of differentiation 34 （CD34） are important signaling proteins involved in angiogenesis. Many studies have demonstrated that VEGF and CD34 are related to tumor progression. This study focused on the relationship between VEGF, CD34, and perioperative hemorrhage in patients with gastric cancer. Methods： To observe the relationship between VEGF and CD34, we tracked 112 patients with advanced gastric cancer for 5 years to assess factors related to hemorrhage, using immunohistochemistry. The results were subjected to statistical analysis using a 2 × 2 contingency table, logistic regression, and receiver operating characteristic （ROC） test. Results： The concentrations of VEGF and CD34 were critically correlated with perioperative hemorrhage and neural invasion in patients with gastric cancer （P 〈 0.05）. Expression of VEGF and CD34 was related （P 〈 0.05, χ2 = 6.834）. VEGF and CD34 co-expression strongly increased the risk of preoperative bleeding （area under the ROC curve 〉0.7, P 〈 0.05）. Conclusions： Expression of VEGF and CD34 was critically correlated with perioperative hemorrhage in gastric cancer patients. Co-expression of VEGF and CD34 could be an effective indicator for evaluating the risk ofperioperative bleeding in gastric cancer patients.展开更多
Aim To study the proliferative effeet of hydroxysaftlor yellow A （HSYA） on cultured canine aortic endothelial cell （VEC） in normoxic （21% O2 ） or hypoxic （10% O2 ） culture and the underlying mechanism. Methods...Aim To study the proliferative effeet of hydroxysaftlor yellow A （HSYA） on cultured canine aortic endothelial cell （VEC） in normoxic （21% O2 ） or hypoxic （10% O2 ） culture and the underlying mechanism. Methods The endothelial cells were scratched from trypsined canine aorta endothelium. HSYA was added to the cells at final concentrations of 1 × 10^-3, 1 × 10^-4 and 1 × 10^-5 mol· L^-1, respectively. VEGF （2.6 × 10^-7 mol· L^-1 ）-treated cells were used as the positive control. The proliferative effect of HSYA on VEC was determined at 48, 72, 96, and 120 h in normoxic culture by MTI＂ assay. Similarly, the proliferation of VEC was determined at 12, 24, 48, and 72 h in hypoxic culture by MTF assay. The effects of HSYA on VEC proliferation and VEGF secretion were investigated by MTr and ELISA assays at the presence of the antibodies to VEGF and VEGF receptors. Results Pretreatment with HSYA at concentrations of 1 × 10^-3 and 1 × 10^-4 mol· L^-1 enhanced VEC proliferation in normoxic culture. The most significant enhancing effect of HSYA on VEC proliferation was achieved at 24, 48, and 72 h in hypoxic culture in concentration-dependent and time-dependent manner. HSYA at 1 × 10^-3 mol·L^-1 showed a potency similar to VEGF at 2.6 × 10^-7 mol·L^-1 . Pretreatment with the antibodies of Flt-1, KDR or VEGF blocked the proliferative effect of HSYA with similar potencies. Antibodies of Fit-1 or VEGF antagonized the promoting effect of HSYA on VEGF secretion. Conclusion HSYA promotes VEC proliferation either in normoxic or hypoxic culture, especially in the latter condition. This effect of HSYA is at least partly mediated by VEGF and VEGF receptor.展开更多
Tumor growth and metastasis depend on the establishment of tumor vasculature to provide oxygen,nutrients,and other essential factors.The well-known vascular endothelial growth factor(VEGF) signaling is crucial for spr...Tumor growth and metastasis depend on the establishment of tumor vasculature to provide oxygen,nutrients,and other essential factors.The well-known vascular endothelial growth factor(VEGF) signaling is crucial for sprouting angiogenesis as well as recruitment of circulating progenitor endothelial cells to tumor vasculature,which has become therapeutic targets in clinical practice.However,the survival benefits gained from targeting VEGF signaling have been very limited,with the inevitable development of treatment resistance.In this article,we discuss the most recent findings and understanding on how solid tumors evade VEGF-targeted therapy,with a special focus on vessel co-option,vessel remodeling,and tumor cell-derived vasculature establishment.Vessel co-option may occur in tumors independently of sprouting angiogenesis,and sprouting angiogenesis is not always required for tumor growth.The differences between vessel-like structure and tubule-like structure formed by tumor cells are also introduced.The exploration of the underlying mechanisms of these alternative angiogenic approaches would not only widen our knowledge of tumor angiogenesis but also provide novel therapeutic targets for better controlling cancer growth and metastasis.展开更多
The regenerating islet-derived members （Reg）, a group of small secretory proteins, which are involved in cell proliferation or differentiation in digestive organs, are upregulated in several gastrointestinal cancers...The regenerating islet-derived members （Reg）, a group of small secretory proteins, which are involved in cell proliferation or differentiation in digestive organs, are upregulated in several gastrointestinal cancers, functioning as trophic or antiapoptotic factors. Regenerat- ing islet-derived type Ⅳ （RegⅣ）, a member of the Reg gene family, has been reported to be overexpressed in gastroenterological cancers. RegIV overexpression in tumor cells has been associated with carcinogen- esis, cell growth, survival and resistance to apoptosis. Cancer tissue expressing RegIV is generally associated with more malignant characteristics than that with- out such expression, and RegⅣ is considered a novel prognostic factor as well as diagnostic marker in some gastroenterological cancers. We previously investigated the expression levels of RegⅣ mRNA of 202 surgical colorectal cancer specimens with quantitative real-time reverse-transcriptase polymerase chain reaction and reported that a higher level of RegⅣ gene expression was a significant independent predictor of colorec- tal cancer. The biologic functions of RegⅣ protein in cancer tissue, associated with carcinogenesis, anti- apoptosis and invasiveness, are being elucidated by molecular investigations using transfection techniques or neutralizing antibodies of RegIV, and the feasibility of antibody therapy targeting RegIV is being assessed. These studies may lead to novel therapeutic strate- gies for gastroenterological cancers expressing RegⅣ. This review article summarizes the current information related to biological functions as well as clinical impor- tance of RegⅣ gene to clarify the significance of Reg~ expression in gastroenterological cancers.展开更多
In the present study, we constructed a lentivirus, FIV-CMV-GFP-miR-7-3, containing the microRNA-7-3 gene and the green fluorescent protein gene, and used it to transfect human glioma U251 cells. Fluorescence microscop...In the present study, we constructed a lentivirus, FIV-CMV-GFP-miR-7-3, containing the microRNA-7-3 gene and the green fluorescent protein gene, and used it to transfect human glioma U251 cells. Fluorescence microscopy showed that 80% of U251 cells expressed green fluorescence. Real-time reverse transcription PCR showed that microRNA-7-3 RNA expression in U251 cells was significantly increased. Proliferation was slowed in transfected U251 cells, and most cells were in the G1 phase of the cell cycle. In addition, the expression of the serine/threonine protein kinase 2 was decreased. Results suggested that transfection with a lentivirus carrying microRNA-7-3 can effectively suppress epidermal growth factor receptor pathway activity in U251 cells, arrest cell cycle transition from GI phase to S phase and inhibit glioma cell growth.展开更多
基金Supported by The "Tenth Five-Year Plan" Research Foundation for the Key Constructional Project ("211 Project") of Zhengzhou University, He'nan Province, China
文摘AIM: To explore the expression of reversion inducing cysteine-rich protein with Kazal motifs (RECK), vascular endothelial growth factor (VEGF) and endoglin (CD105) protein and its correlation with occurrence, development, invasion and metastasis in esophageal squamous cell carcinoma (ESCC). METHODS: Streptavidin-peroxidase (SP) immunohisto- chemistry was used to detect expression of RECK and VEGF in 62 cases of ESCC, 31 cases of adjacent atypical hyperplastic epithelium and 62 cases of normal esophageal epithelium. CD105 Mb was used to assess microvessel density (MVD). RESULTS: The expression of RECK was closely correlated with histological grade, infiltrative depth and lymphatic metastasis in ESCC (P < 0.05). The expression of RECK decreased during cancer development: normal esophageal epithelium (85.5%, 53/62), adjacent atypical hyperplastic epithelium (71.0%, 22/31), and carcinoma (59.7%, 37/62). There was a significant difference among the groups (P < 0.05). The expression of VEGF protein was closely correlated with infiltrative depth and lymphatic metastasis in ESCC (P < 0.05). The expression of VEGF protein increased during cancer development: normal esophageal epithelium (29.0%, 18/62), adjacent atypical hyperplastic epithelium (54.8%, 17/31), and carcinoma (67.7%, 42/62). There was a significant difference among the groups (P < 0.05). MVDCD105 increased in accordance with histological grade, butthere was no significant difference (grade Ⅰ, 36.92 ± 10.85; grade Ⅱ, 37.65 ± 9.50; and grade Ⅲ, 38.06 ± 12.19). The MVDCD105 was closely correlated with infiltration and lymphatic metastasis in ESCC (P < 0.05). The expression of RECK was inversely correlated with the expression of VEGF and CD105. CONCLUSION: RECK, VEGF and CD105 play important roles in the infiltration, metastasis and carcinogenesis in esophageal carcinoma. Angiogenesis in ESCC may be promoted by over-expression of CD105.
基金supported by a grant from Shengjing Hospital,China Medical University,China,No.201010252
文摘Percutaneous microballoon compression of the trigeminal ganglion is a brand new operative technique for the treatment of trigeminal neuralgia. However, it is unclear how the procedure mediates pain relief, and there are no standardized criteria, such as compression pressure, com- pression time or balloon shape, for the procedure. In this study, percutaneous microballoon compression was performed on the rabbit trigeminal ganglion at a mean inflation pressure of 1,005 ＋ 150 mmHg for 2 or 5 minutes. At 1, 7 and 14 days after percutaneous microballoon compression, the large-diameter myelinated nerves displayed axonal swelling, rupture and demy- elination under the electron microscope. Fragmentation of myelin and formation of digestion chambers were more evident after 5 minutes of compression. Image analyzer results showed that the diameter of trigeminal ganglion cells remained unaltered after compression. These experi- mental findings indicate that a 2-minute period of compression can suppress pain transduction. Immunohistochemical staining revealed that vascular endothelial growth factor expression in the ganglion cells and axons was significantly increased 7 days after trigeminal ganglion compression, however, the changes were similar after 2-minute compression and 5-minute compression. The upregulated expression of vascular endothelial growth factor in the ganglion cells after percu- taneous microballoon compression can promote the repair of the injured nerve. These findings suggest that long-term compression is ideal for patients with recurrent trigeminal neuralgia.
文摘Background Sterol regulatory element binding protein （SREBP）-2 plays a key role in lipid homeostasis by stimulating gene expression of cholesterol biosynthetic pathways. The insulin-like growth factor binding protein （IGFBP） family regulates growth and metabolism, especially bone cell metabolism, and correlates with osteonecrosis. However, association of their gene polymorphisms with risk of avascular necrosis of the femoral head （ANFH） has rarely been reported. We determined whether SREBP-2 and IGFBP-3 gene polymorphisms were associated with increased ANFH risk in the Chinese population. Methods Two single nucleotide polymorphisms of SREBP2 gene, rs2267439 and rs2267443, and one of IGFBP-3 gene, rs2453839, were selected and genotyped in 49 ANFH patients and 42 control individuals by direct sequencing assay. Results The frequencies of rs2267439 TT and rs2267443 GA of SREBP2 and rs2453839 TT and CT of IGFBP-3 in the ANFH group showed increased and decreased tendencies （against normal control group）, respectively. Interaction analysis of genes revealed that the frequency of carrying rs2267439 TT and rs2267443 GA genotypes of SREBF-2 in ANFH patients was significantly higher than in the control group （P 〈0.05）. Association analysis between polymorphisms and clinical phenotype demonstrated that the disease course in ANFH patients with the rs2453839 TT genotype of IGFBP-3 was significantly shorter than that of CT＋CC carriers （P 〈0.01）. CT＋CC genotype frequency in patients with stage Ill/IV bilateral hip lesions was significantly higher than in those with stage Ill/IV unilateral lesions and stage II/111 bilateral lesions （P 〈0.05-0.02）. Conclusions Our results suggested that interaction of SREBP-2 gene polymorphisms and the relationship between the polymorphisms and clinical phenotype of IGFBP-3 were closely related to increased ANFH risk in the Chinese population. The most significant finding was that the CT＋CC genotype carriers of IGFBP-3 rs2453839 were highly associated with t
文摘Neuroprotection by ischemic preconditioning has been confirmed by many studies, but the precise mechanism remains unclear. In the present study, we performed cerebral ischemic pre- conditioning in rats by simulating a transient ischemic attack twice （each a 20-minute occlusion of the middle cerebral artery） before inducing focal cerebral infarction （2 hour occlusion-reper- fusion in the same artery）. We also explored the mechanism underlying the neuroprotective effect of ischemic preconditioning. Seven days after ocdusion-reperfusion, tetrazolium chloride staining and immunohistochemistry revealed that the infarct volume was significantly smaller in the group that underwent preconditioning than in the model group. Furthermore, vascular endothelial growth factor immunoreactivity was considerably greater in the hippocampal CA3 region of preconditioned rats than model rats. Our results suggest that the protective effects of ischemic preconditioning on focal cerebral infarction are associated with upregulation of vascu- lar endothelial growth factor.
文摘AIM: To improve osteogenic differentiation and attachment of cells.METHODS: An electronic search was conducted inPub Med from January 2004 to December 2013. Studies which performed smart modifications on conventional bone scaffold materials were included. Scaffolds with controlled release or encapsulation of bioactive molecules were not included. Experiments which did not investigate response of cells toward the scaffold(cell attachment, proliferation or osteoblastic differentiation) were excluded. RESULTS: Among 1458 studies, 38 met the inclusion and exclusion criteria. The main scaffold varied extensively among the included studies. Smart modifications included addition of growth factors(group Ⅰ-11 studies), extracellular matrix-like molecules(group Ⅱ-13 studies) and nanoparticles(nano-HA)(group Ⅲ-17 studies). In all groups, surface coating was the most commonly applied approach for smart modification of scaffolds. In group I, bone morphogenetic proteins were mainly used as growth factor stabilized on polycaprolactone(PCL). In group Ⅱ, collagen 1 in combination with PCL, hydroxyapatite(HA) and tricalcium phosphate were the most frequent scaffolds used. In the third group, nano-HA with PCL and chitosan were used the most. As variable methods were used, a thorough and comprehensible compare between the results and approaches was unattainable.CONCLUSION: Regarding the variability in methodology of these in vitro studies it was demonstrated that smart modification of scaffolds can improve tissue properties.
基金Supported by The NIH grants,Nos.GM104934,EY020900 and EY021725(NEI Core)Chinese National Natural Science Foundation grant,No.81200699grants from Presbyterian Health Foundation and Oklahoma Center for Adult Stem Cell Research and an endowment from Choctaw Nation(to Le YZ)
文摘Müller cells are macroglia and play many essential roles as supporting cells in the retina.To respond to pathological changes in diabetic retinopathy(DR),a major complication in the eye of diabetic patients,retinal Müller glia produce a high level of vascular endothelial growth factor(VEGF or VEGF-A).As VEGF is expressed by multiple retinal cell-types and Müller glia comprise only a small portion of cells in the retina,it has been a great challenge to reveal the function of VEGF or other globally expressed proteins produced by Müller cells.With the development of conditional gene targeting tools,it is now possible to dissect the function of Müller cell-derived VEGF in vivo.By using conditional gene targeting approach,we demonstrate that Müller glia are a major source of retinal VEGF in diabetic mice and Müller cell-derived VEGF plays a significant role in the alteration of protein expression and peroxynitration,which leads to retinal inflammation,neovascularization,vascular leakage,and vascular lesion,key pathological changes in DR.Therefore,Müller glia are a potential cellular target for the treatment of DR,a leading cause of blindness.
基金supported by the National Natural Science Foundation of ChinaNo.81100922
文摘Nerve growth factor（NGF） plays an important role in promoting neuroregeneration after peripheral nerve injury. However, its effects are limited by its short half-life; it is therefore important to identify an effective mode of administration. High-frequency ultrasound（HFU） is increasingly used in the clinic for high-resolution visualization of tissues, and has been proposed as a method for identifying and evaluating peripheral nerve damage after injury. In addition, HFU is widely used for guiding needle placement when administering drugs to a specific site. We hypothesized that HFU guiding would optimize the neuroprotective effects of NGF on sciatic nerve injury in the rabbit. We performed behavioral, ultrasound, electrophysiological, histological, and immunohistochemical evaluation of HFU-guided NGF injections administered immediately after injury, or 14 days later, and compared this mode of administration with intramuscular NGF injections. Across all assessments, HFU-guided NGF injections gave consistently better outcomes than intramuscular NGF injections administered immediately or 14 days after injury, with immediate treatment also yielding better structural and functional results than when the treatment was delayed by 14 days. Our findings indicate that NGF should be administered as early as possible after peripheral nerve injury, and highlight the striking neuroprotective effects of HFU-guided NGF injections on peripheral nerve injury compared with intramuscular administration.
文摘AIM： To investigate the effects of experimental partial hepatectomy and normothermic ischemia-reperfusion damage on the time course of the expression of four different growth factor receptors in liver regeneration. This is relevant due to the potential therapeutic use of growth factors in stimulating liver regeneration. METHODS： For partial hepatectomy （PH） 80% of the liver mass was resected in Sprague Dawley rats. Ischemia and reperfusion （I/R） were induced by occlusion of the portal vein and the hepatic artery for 15 min. The epidermal growth factor receptor, hepatic growth factor receptor, fibroblast growth factor receptor and tumour necrosis factor receptor-1 were analysed by immunohistochemistry up to 72 h after injury. Quantitative RT-PCR was performed at the time point of minimal receptor expression （24 h）. RESULTS： In immunohistochemistry, EGFR, HGFR, FGFR and TNFR1 showed biphasic kinetics after partial hepatectomy with a peak up to 12 h, a nadir after 24 h and another weak increase up to 72 h. During liver regeneration, after ischemia and reperfusion, the receptor expression was lower; the nadir at 24 h after reperfusion was the same. To evaluate whether this nadir was caused by a lack of mRNA transcription, or due to a posttranslational regulation, RT-PCR was performed at 24 h and compared to resting liver. In every probe there was specific mRNA for the receptors. EGFR, FGFR and TNFR1 mRNA expression was equal or lower than in resting liver, HGFR expression after I/R was stronger than in the control. CONCLUSION： At least partially due to a post-transcriptional process, there is a nadir in the expression of the analysed receptors 24 h after liver injury. Therefore, a therapeutic use of growth factors to stimulate liverregeneration 24 h after the damage might be not successful.
基金Supported by the National 863 Project, No. 2001AA215131 and No. 2002AA2Z3318
文摘AIM： To study the protective effect of non-mitogenic human acidic fibroblast growth factor （FGF） on cardiac oxidative injury in vivo. METHODS： Ventricular cardiomyocytes were isolated from 1- to 3-d-old neonatal SD mice and cultured in Dulbecco＇s minimum essential medium supplemented with 15% fetal bovine serum under an atmosphere of 50 mL/L CO2-95% air at 37℃, as well as assessed by immunooltochemical assay. We constructed the cardiomyoolte injury model by exposure to a certain concentration of H2O2. Cellular viability, superoxide dismutase （SOD） activity, leakage of maleic dialdehyde and anti-apoptosis effect were included to evaluate the cardiac protective effect of non-mitogenic human acidic FGF. RESULTS： Over 50% of the cardiomyocytes beat spontaneously on the 2nd d of culture and synchronously beat after being cultured for 3 d. Forty-eight hours after plating was completed, the purity of such cultures was 95% myocytes, assessed by an immunocytochemical assay. Cellular viability dramatically decreased with the increasing of the concentration of H2O2. Non-mitogenic human acidic FGF showed significant resistance to thetoxic effect of H2O2, significantly increased the cellular viability as well as the activity of SOD, and dramatically decreased the leakage of maleic dialdehyde as well as the cellular apoptosis rate. CONCLUSION： Hydrogen peroxide shows strong cytotoxicity to the cultured cardiac myocytes, and non-mitogenic human acidic FGF shows strong cardio-protective effect when exposed to a certain concentration of H2O2.
基金Supported by the National Natural Sciences Foundation of China(No.81470171)Basic Science Research Fund from Ministry of Finance of China(No.ZZ2012008 and ZZ2015014)
文摘OBJECTIVE: To investigate the neural differentiation capacity of water extraction of velvet antler.METHODS: Velvet antler(Cervus Nippon Temminck) polypeptide(VAP) was used to differentiate neural stem cells(NSCs) towards neurons in the study. Firstly, we obtain the polypeptides of VAP by water extraction. Secondly, we observed the morphology, assayed the factors in the media by enzyme-linked immunosorbent assay, and detected the special neural molecules by immuno fl uorescence staining. NSCs were cultured on the cell climbing film. After neuronal differentiation, differentiated NSCs were mounted for immunocytochemistry with immunofluorescence technique.RESULTS: The differentiating cells look like neuron,some special factors, such as Glial cell line-derived neurotrophic factor, nerve growth factor, in the media can be detected while differentiated neuron-like cells can express the special neural molecules.CONCLUSION: Differentiation of NSCs towards neurons can be induced by velvet antler polypeptide.
基金Supported by A grant of "Department of Health,Government of Navarra,Spain (23/2009)"
文摘AIM： To investigate the angiogenesis-related protein expression profile characterizing metastatic colorectal cancer （mCRC） with the aim of identifying prognostic markers.METHODS： The expression of 44 angiogenesis- secreted factors was measured by a novel cytokine antibody array methodology. The study evaluated vas- cular endothelial growth factor （VEGF） and its soluble vascular endothelial growth factor receptor （sVEGFR）-I protein levels by enzyme immunoassay （EIA） in a panel of 16 CRC cell lines, mRNA VEGF and VEGF-A isoforms were quantified by quantitative reverse-transcription polymerase chain reaction （Q-RT-PCR） and vascular en- dothelial growth factor receptor （VEGFR）-2 expressionwas analyzed by flow cytometry.
文摘Background： Angiogenesis is the formation of new blood vessels to supply nutrients to tumors. Vascular endothelial growth factor （VEGF） and cluster of differentiation 34 （CD34） are important signaling proteins involved in angiogenesis. Many studies have demonstrated that VEGF and CD34 are related to tumor progression. This study focused on the relationship between VEGF, CD34, and perioperative hemorrhage in patients with gastric cancer. Methods： To observe the relationship between VEGF and CD34, we tracked 112 patients with advanced gastric cancer for 5 years to assess factors related to hemorrhage, using immunohistochemistry. The results were subjected to statistical analysis using a 2 × 2 contingency table, logistic regression, and receiver operating characteristic （ROC） test. Results： The concentrations of VEGF and CD34 were critically correlated with perioperative hemorrhage and neural invasion in patients with gastric cancer （P 〈 0.05）. Expression of VEGF and CD34 was related （P 〈 0.05, χ2 = 6.834）. VEGF and CD34 co-expression strongly increased the risk of preoperative bleeding （area under the ROC curve 〉0.7, P 〈 0.05）. Conclusions： Expression of VEGF and CD34 was critically correlated with perioperative hemorrhage in gastric cancer patients. Co-expression of VEGF and CD34 could be an effective indicator for evaluating the risk ofperioperative bleeding in gastric cancer patients.
文摘Aim To study the proliferative effeet of hydroxysaftlor yellow A （HSYA） on cultured canine aortic endothelial cell （VEC） in normoxic （21% O2 ） or hypoxic （10% O2 ） culture and the underlying mechanism. Methods The endothelial cells were scratched from trypsined canine aorta endothelium. HSYA was added to the cells at final concentrations of 1 × 10^-3, 1 × 10^-4 and 1 × 10^-5 mol· L^-1, respectively. VEGF （2.6 × 10^-7 mol· L^-1 ）-treated cells were used as the positive control. The proliferative effect of HSYA on VEC was determined at 48, 72, 96, and 120 h in normoxic culture by MTI＂ assay. Similarly, the proliferation of VEC was determined at 12, 24, 48, and 72 h in hypoxic culture by MTF assay. The effects of HSYA on VEC proliferation and VEGF secretion were investigated by MTr and ELISA assays at the presence of the antibodies to VEGF and VEGF receptors. Results Pretreatment with HSYA at concentrations of 1 × 10^-3 and 1 × 10^-4 mol· L^-1 enhanced VEC proliferation in normoxic culture. The most significant enhancing effect of HSYA on VEC proliferation was achieved at 24, 48, and 72 h in hypoxic culture in concentration-dependent and time-dependent manner. HSYA at 1 × 10^-3 mol·L^-1 showed a potency similar to VEGF at 2.6 × 10^-7 mol·L^-1 . Pretreatment with the antibodies of Flt-1, KDR or VEGF blocked the proliferative effect of HSYA with similar potencies. Antibodies of Fit-1 or VEGF antagonized the promoting effect of HSYA on VEGF secretion. Conclusion HSYA promotes VEC proliferation either in normoxic or hypoxic culture, especially in the latter condition. This effect of HSYA is at least partly mediated by VEGF and VEGF receptor.
基金supported by grants from the National Natural Science Foundation of China(No.81472386,81472380,81272340,and 81030043)the National High Technology Research and Development Program of China (863 Program,No.2012AA02A501)
文摘Tumor growth and metastasis depend on the establishment of tumor vasculature to provide oxygen,nutrients,and other essential factors.The well-known vascular endothelial growth factor(VEGF) signaling is crucial for sprouting angiogenesis as well as recruitment of circulating progenitor endothelial cells to tumor vasculature,which has become therapeutic targets in clinical practice.However,the survival benefits gained from targeting VEGF signaling have been very limited,with the inevitable development of treatment resistance.In this article,we discuss the most recent findings and understanding on how solid tumors evade VEGF-targeted therapy,with a special focus on vessel co-option,vessel remodeling,and tumor cell-derived vasculature establishment.Vessel co-option may occur in tumors independently of sprouting angiogenesis,and sprouting angiogenesis is not always required for tumor growth.The differences between vessel-like structure and tubule-like structure formed by tumor cells are also introduced.The exploration of the underlying mechanisms of these alternative angiogenic approaches would not only widen our knowledge of tumor angiogenesis but also provide novel therapeutic targets for better controlling cancer growth and metastasis.
文摘The regenerating islet-derived members （Reg）, a group of small secretory proteins, which are involved in cell proliferation or differentiation in digestive organs, are upregulated in several gastrointestinal cancers, functioning as trophic or antiapoptotic factors. Regenerat- ing islet-derived type Ⅳ （RegⅣ）, a member of the Reg gene family, has been reported to be overexpressed in gastroenterological cancers. RegIV overexpression in tumor cells has been associated with carcinogen- esis, cell growth, survival and resistance to apoptosis. Cancer tissue expressing RegIV is generally associated with more malignant characteristics than that with- out such expression, and RegⅣ is considered a novel prognostic factor as well as diagnostic marker in some gastroenterological cancers. We previously investigated the expression levels of RegⅣ mRNA of 202 surgical colorectal cancer specimens with quantitative real-time reverse-transcriptase polymerase chain reaction and reported that a higher level of RegⅣ gene expression was a significant independent predictor of colorec- tal cancer. The biologic functions of RegⅣ protein in cancer tissue, associated with carcinogenesis, anti- apoptosis and invasiveness, are being elucidated by molecular investigations using transfection techniques or neutralizing antibodies of RegIV, and the feasibility of antibody therapy targeting RegIV is being assessed. These studies may lead to novel therapeutic strate- gies for gastroenterological cancers expressing RegⅣ. This review article summarizes the current information related to biological functions as well as clinical impor- tance of RegⅣ gene to clarify the significance of Reg~ expression in gastroenterological cancers.
基金supported by the Science and Technology Foundation Program of Jiangsu Province(Tumorigenic nucleostemin genes and adenovirus-based RNA interference targeting to brain tumor stem cell the rapy),No.BK2007072
文摘In the present study, we constructed a lentivirus, FIV-CMV-GFP-miR-7-3, containing the microRNA-7-3 gene and the green fluorescent protein gene, and used it to transfect human glioma U251 cells. Fluorescence microscopy showed that 80% of U251 cells expressed green fluorescence. Real-time reverse transcription PCR showed that microRNA-7-3 RNA expression in U251 cells was significantly increased. Proliferation was slowed in transfected U251 cells, and most cells were in the G1 phase of the cell cycle. In addition, the expression of the serine/threonine protein kinase 2 was decreased. Results suggested that transfection with a lentivirus carrying microRNA-7-3 can effectively suppress epidermal growth factor receptor pathway activity in U251 cells, arrest cell cycle transition from GI phase to S phase and inhibit glioma cell growth.
