Perillyl alcohol modulates activation, permeability and integrity of human brain endothelial cells induced by Plasmodium falciparum

BACKGROUND Cerebral malaria (CM) is a severe immunovasculopathy caused for Plasmodium falciparum infection, which is characterised by the sequestration of parasitised red blood cells (pRBCs) in brain microvessels. Previous studies have shown that some terpenes, such as perillyl alcohol (POH), exhibit a marked efficacy in preventing cerebrovascular inflammation, breakdown of the brain-blood barrier (BBB) and brain leucocyte accumulation in experimental CM models. OBJECTIVE To analyse the effects of POH on the endothelium using human brain endothelial cell (HBEC) monolayers co-cultured with pRBCs. METHODOLOGY The loss of tight junction proteins (TJPs) and features of endothelial activation, such as ICAM-1 and VCAM-1 expression were evaluated by quantitative immunofluorescence. Microvesicle (MV) release by HBEC upon stimulation by P. falciparum was evaluated by flow cytometry. Finally, the capacity of POH to revert P. falciparum-induced HBEC monolayer permeability was examined by monitoring trans-endothelial electrical resistance (TEER). FINDINGS POH significantly prevented pRBCs-induced endothelial adhesion molecule (ICAM-1, VCAM-1) upregulation and MV release by HBEC, improved their trans-endothelial resistance, and restored their distribution of TJPs such as VE-cadherin, Occludin, and JAM-A. CONCLUSIONS POH is a potent monoterpene that is efficient in preventing P. falciparum-pRBCs-induced changes in HBEC, namely their activation, increased permeability and alterations of integrity, all parameters of relevance to CM pathogenesis.

Role of HBV DNA polymerase in mediating the immune escape of tumor cells in HBV-related hepatocellular carcinoma / 临床肝胆病杂志

ObjectiveTo determine whether HBV DNA polymerase is associated with T-cell failure and thus mediates the immune escape of HBV-related hepatocellular carcinoma （HCC） tumor cells， and to investigate the specific molecular mechanisms. MethodsLiver cancer cell lines Huh7 and HepG2 stably transfected with HBV DNA polymerase expression plasmid with Flag （Flag-HBV-P） and intercellular adhesion molecule-1 （ICAM1） were co-cultured with Jurkat cells， and MTT assay， qRT-PCR， and ELISA were used to measure Jurkat cell proliferation， activation （CD69 expression）， and secretion of the cytokine IFN-γ. RNA-seq was used to screen for differentially expressed immune-associated molecules between stably transfected cell lines and control cells， and mRNA half-life and protein half-life assays were used to determine the specific levels of the immune-associated molecules that were affected by HBV DNA polymerase. Related websites were used to predict the transcription factors that may bind to the promoter region of this immune-associated molecule， Western blot was used to verify the effect of transcription factors on the immune-associated molecule， and rescue experiment was used to determine whether HBV DNA polymerase affects the expression level of the immune-associated molecule through this transcription factor. The independent-samples t test was used for comparison between two groups. ResultsThe experimental group had significant reductions in Jurkat cell proliferation， activation， and cytokine secretion compared with the control group （all P<0.01）. Compared with the control group， the experimental group （Huh7 and HepG2 cell lines） had significant reductions in the mRNA and protein expression levels of ICAM1 （all P<0.01）. Website prediction identified the ICAM1 promoter and preliminarily highlighted NFKB1， RELA， and STAT3. Compared with the control group， the experimental group （Huh7 and HepG2 cell lines） had a significant reduction in the protein expression level of p65 （all P<0.01）. After p65 overexpression， there was a significant increase in the protein expression level of ICAM1， and after the expression of p65 was reduced， there was a significant reduction in the protein expression level of ICAM1 （all P<0.01）. In the rescue experiment， there was no significant difference in the protein expression level of ICAM1 between the control group and the experimental group after p65 overexpression （all P>0.05）. After the overexpression of ICAM1， there were no significant differences in the proliferation， activation， and cytokine secretion of Jurkat cells between the control group and the experimental group （Huh7 and HepG2 cell lines） （all P>0.05）. ConclusionHBV DNA polymerase downregulates the level of ICAM1 to mediate HCC immune escape by inhibiting the expression of p65 in NF-κB.

Early and late interventional embolization can improve neurological function, mental state and living ability of patients with intracranial aneurysm / 中国基层医药

Objective:To investigate the application value of early and late interventional embolization in intracranial aneurysms.Methods:Eighty-two patients with intracranial aneurysm who received treatment in Wenzhou People's Hospital from October 2015 to February 2020 were included in this study. These patients were divided into early (≤ 3 days) and late (> 3 days) groups, with 41 patients in each group, according to time from disease onset to surgery. The early group was subjected to early interventional embolization, and the late group was treated with late interventional embolization. The effects of embolization and National Institutes of Health Stroke Scale score pre- and post-treatment, as well as modified Barthel index, Mini-Mental State Exam score, matrix metalloproteinase-9 level, and soluble intercellular adhesion molecule-1 level post-treatment and prognosis were compared between the two groups.Results:The embolization effects in the early group were statistically superior to those in the late group ( P = 0.046). After treatment, National Institutes of Health Stroke Scale score in the early group was significantly lower than that in the late group [(4.02 ± 1.64) points vs. (6.81 ± 2.02) points, t = 6.86, P < 0.01]. Mini-Mental State Exam score and modified Barthel index in the early group were (28.09 ± 1.35) points and (81.12 ± 9.67) points, respectively, which were significantly higher than (26.01 ± 1.19) points and (73.02 ± 8.19) points in the late group ( t = 7.40, 4.09, both P < 0.001). After treatment, matrix metalloproteinase-9 and soluble intercellular adhesion molecule-1 levels in the early group were (420.33 ± 29.40) μg/L and (403.70 ± 23.28) ug/L, respectively, which were significantly lower than (491.30 ± 31.19) μg/mL and (496.37 ± 30.46) μg/L in the late group ( t = 10.60, 15.47, both P < 0.001). Prognosis in the early group was superior to that in the late group ( P = 0.049). Conclusion:Early interventional embolization has better efficacy than late interventional embolization in the treatment of intracranial aneurysm. The former can effectively improve neurological function and mental state, enhance living ability, and improve prognosis, which may be related to the regulation of matrix metalloproteinase-9 and soluble intercellular adhesion molecule-1 levels.

Expression and significance of L1 cell adhesion molecule and transforming growth factor-β1 in pancreatic cancer tissue / 临床肝胆病杂志

ObjectiveTo investigate the expression of L1 cell adhesion molecule (L1CAM) and transforming growth factor-β1 (TGFβ1) in pancreatic cancer tissue and their association with the prognosis of pancreatic cancer. MethodsHistological specimens were collected from 125 patients with pancreatic cancer who underwent surgical resection in The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University Cancer Hospital, and Wuming Hospital of Guangxi Medical University from January 2015 to January 2018. Immunohistochemistry was used to measure the expression of L1CAM and TGFβ1 in all specimens, and the association of the expression of L1CAM and TGFβ1 with clinical indices, survival, and prognosis was analyzed. The t-test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups; the Cox proportional-hazards regression model was used to investigate the influencing factors for the survival of patients with pancreatic cancer; the Kaplan-Meier survival analysis was used to evaluate the survival of patients with different expression levels of L1CAM and TGFβ1. ResultsThe high protein expression rate of L1CAM in pancreatic cancer tissue was significantly higher than that in adjacent tissue (75.20% vs 20.00%, χ2=76.352, P＜0.001). The high protein expression rate of TGFβ1 in pancreatic cancer tissue was significantly higher than that in adjacent tissue (8160% vs 23.20%, χ2=85.461, P＜0.001). The protein expression of L1CAM was positively correlated with that of TGFβ1 in pancreatic cancer (r=0.492, P＜0.001). The protein expression of L1CAM and TGFβ1 were associated with tumor size, degree of tumor differentiation, TNM stage, lymph node metastasis, intravascular tumor thrombus, and perineural invasion (all P＜0.05). The patients with high protein expression of L1CAM or TGFβ1 had a significantly lower overall survival rate than those with low expression (χ2=54661 and 39597, both P＜0.001). ConclusionL1CAM and TGFβ1 proteins are highly expressed in pancreatic cancer tissue and may be associated with poor prognosis by promoting lymphatic metastasis and hematogenous metastasis. L1CAM and TGFβ1 proteins play an important role in the development, progression, and metastasis of pancreatic cancer.

Correlation between adhesion molecules on the surface of red blood cell membrane and red blood cell lifespan / 中国输血杂志

【Objective】 To explore the correlation between red blood cell lifespan and adhesion molecules on the surface of red blood cell membrane, in order to establish a method to detect the duration of red blood cell storage. 【Methods】 10 samples(10 mL each) of fresh red blood cell, collectedf rom 10 healthy voluntary blood donors, were divided into 5 age groups (layers) by Percoll density gradient centrifugation. The expression of CD47, CD44 and CD147 on the surface of red blood cell membrane in each layer was detected using flow cytometry. The variance of protein expression in each layer of red blood cells was analyzed by SPSS statistical software. 【Results】 The expression levels (%) of 3 adhesion molecules on the surface of red blood cell membranes from young to old were CD47: 14.44±2.61, 9.30±1.75, 7.84±1.49, 6.54±1.32 and 5.53±1.12 (P<0.01); CD44: 25.01±1.94, 19.22±1.52, 17.10±1.28, 15.18±1.11 and 13.56±1.08 (P<0.01); CD147: 33.46±1.99, 28.31±2.95, 23.83±1.59, 20.40±1.56 and 18.03±1.65 (P<0.01). 【Conclusion】 The expression levels of CD47, CD44 and CD147 on the surface of red blood cell membranes have showed a downward trend as the storage extended. These three protein adhesion molecules have showed a correlation with red blood cells lifespan, and could be used as detection markers of cell age.

Clinical value of serum cell adhesion molecules in predicting of acute kidney injury in patients with severe sepsis / 中国医师进修杂志

Objective@#To assess the clinical value of serum cell adhesion molecules in predicting of acute kidney injury (AKI) in patients with severe sepsis.@*Methods@#The clinical data of 72 patients with severe sepsis from July 2015 to July 2017 in Sinopharm Dongfeng General Hospital were retrospectively analyzed. Among them, AKI occurred in 45 cases (AKI group), and AKI did not occur in 27 cases (non-AKI group). The clinical data of 2 groups were recorded; the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) on admission were evaluated; the blood routine, serum creatinine, C reactive protein, procalcitonin, lactic acid, intercellular adhesion molecular-1 (ICAM-1), E-selectin, P-selectin and vascular cell adhesion molecule-1 (VCAM-1) were detected.@*Results@#The incidences of infectious shock and respiratory failure, APACHE Ⅱ, SOFA, creatinine, lactic acid, ICAM-1, E-selectin, VCAM-1 in AKI group were significantly higher than those in non-AKI group: 84.4% (38/45) vs. 51.9% (14/27), 51.1% (23/45) vs. 22.2% (6/27), (20.6 ± 2.8) scores vs. (15.9 ± 3.2) scores, (7.4 ± 1.5) scores vs. (4.5 ± 0.7) scores, (131.9 ± 48.7) μmol/L vs. (76.8 ± 10.3)μmol/L, (3.28 ± 0.78) mmol/L vs. (2.64 ± 0.37) mmol/L, (0.93 ± 0.12) mg/L vs. (0.59 ± 0.07) mg/L, (2.25 ± 0.20) mg/L vs. (1.13 ± 0.17) mg/L and (2.65 ± 0.31) mg/L vs. (1.86 ± 0.16) mg/L, and there were statistical differences (P < 0.01 or <0.05); there were no statistical differences in gender, age, basic disease, blood pressure, heart rate, respiratory frequency, infection site, white blood cell, lymphocyte ratio, platelet, blood glucose, C reactive protein, procalcitonin and P-selectin between 2 groups (P>0.05). Pearson correlation analysis result showed that serum ICAM-1, E-selectin, VCAM-1 were positively correlated with serum creatinine (r = 0.625, 0.358 and 0.441; P < 0.05); but there was no correlation between serum lactic acid and serum creatinine (r = 0.146, P > 0.05). Stepwise Logistic regression analysis result showed that creatinine, lactic acid, ICAM-1, E-selectin and VCAM-1 were independent risk factors of AKI in patients with severe sepsis (OR = 2.758, 1.710, 2.955, 1.801 and 2.218; 95% CI 1.845 to 4.371, 1.335 to 2.314, 1.674 to 4.163, 1.572 to 3.235 and 1.339 to 3.752; P < 0.01 or <0.05). The area under curve of serum ICAM-1, E-selectin, VCAM-1 combined detection for predicting of AKI in patients with severe sepsis was 0.876 (95% CI 0.777 to 0.942), with a specificity of 80.0% and a sensitivity of 85.2%.@*Conclusions@#serum ICAM-1, E-selectin, VCAM-1 combined detection can be used as predictor of AKI in patients with severe sepsis.

The relationship between the expression of IL-13 and periostin and the severity of airway remodeling in asthmatic patients / 中国医师杂志

Objective@#By detecting the expression of interleukin-13 (IL-13) and periostin in the airway of asthmatic patients, the pathological changes and pulmonary functions of airway tissues in asthmatic patients were evaluated, and the role of IL-13 and periostin airway remodeling in bronchial asthma was preliminarily explored.@*Methods@#The bronchial tissues adjacent to tumor nest were obtained from 12 patients with lung cancer complicated with bronchial asthma (asthmatic group) and 12 lung cancer patients without bronchial asthma (non-asthmatic group) after lung cancer resection. Pulmonary function was measured for all subjects before surgery. Pathological changes of airway tissues and degree of airway remodeling were assessed by hematoxylin-eosin (H&E) staining, masson′s trichrome staining, and periodic acid-silver methenamine (PASM) staining of paraffin-embedded sections. The expression of IL-13 and periostin in bronchial tissues were evaluated by immunohistochemistry.@*Results@#Values of the forced expiratory volume in 1 second of the predicted value (FEV1% pred) and FEV1/forced vital capacity (FEV1/FVC%) in asthmatic patients were significantly decreased compared with the non-asthmatic patients (P<0.05), indicating that lung function was impaired in asthmatic patients. There was more severe airway remodeling representing as thickening of basement membranes, collagen deposition, and increasing of goblet cells and fibroblasts in asthmatic patients than in non-asthmatic patients (all P<0.05). The expression of IL-13 and periostin were higher in asthmatic tissues than in non-asthmatic tissues (P<0.05). The immunohistochemical expression of IL-13 and periostin in bronchial tissues were positively correlated with the degree of airway remodeling in asthmatic patients, and the expression of IL-13 and periostin in bronchial tissues were positively correlated with each other.@*Conclusions@#The expression of IL-13 and periostin were increased in bronchial tissue in patients with asthma. They work together to promote the occurrence of airway remodeling, which eventually lead to a decline in lung function.

The relationship between the expression of IL-13 and periostin and the severity of airway remodeling in asthmatic patients / 中国医师杂志

Objective By detecting the expression of interleukin-13 (IL-13 and periostin in the airway of asthmatic patients,the pathological changes and pulmonary functions of airway tissues in asthmatic patients were evaluated,and the role of IL-13 and periostin airway remodeling in bronchial asthma was preliminarily explored.Methods The bronchial tissues adjacent to tumor nest were obtained from 12 patients with lung cancer complicated with bronchial asthma (asthmatic group) and 12 lung cancer patients without bronchial asthma (non-asthmatic group) after lung cancer resection.Pulmonary function was measured for all subjects before surgery.Pathological changes of airway tissues and degree of airway remodeling were assessed by hematoxylin-eosin (H&E) staining,masson's trichrome staining,and periodic acid-silver methenamine (PASM) staining of paraffin-embedded sections.The expression of IL-13 and periostin in bronchial tissues were evaluated by immunohistochemistry.Results Values of the forced expiratory volume in 1 second of the predicted value (FEV1％ pred) and FEV1/forced vital capacity (FEV1/FVC％) in asthmatic patients were significantly decreased compared with the non-asthmatic patients (P ＜ 0.05),indicating that lung function was impaired in asthmatic patients.There was more severe airway remodeling representing as thickening of basement membranes,collagen deposition,and increasing of goblet cells and fibroblasts in asthmatic patients than in non-asthmatic patients (all P ＜ 0.05).The expression of IL-13 and periostin were higher in asthmatic tissues than in non-asthmatic tissues (P ＜ 0.05).The immunohistochemical expression of IL-13 and periostin in bronchial tissues were positively correlated with the degree of airway remodeling in asthmatic patients,and the expression of IL-13 and periostin in bronchial tissues were positively correlated with each other.Conclusions The expression of IL-13 and periostin were increased in bronchial tissue in patients with asthma.They work together to promote the occurrence of airway remodeling,which eventually lead to a decline in lung function.

The expression and clinical significance of epithelial cell adhesion molecule and Claudin18 in gastric cancer / 中华老年医学杂志

Objective To investigate the expression and clinical significance of epithelial cell adhesion molecule(EpCAM) and Claudin-18 in gastric cancer.Methods Surgical specimens of gastric cancer were taken from 64 patients.The histological diagnostic criteria were based on WHO standards.Immunohistochemical staining was used to detect expression levels of EpCAM and Claudin-18 in all samples.The relationship between the expression of EpCAM and Claudin-18 and clinicopathological parameters of gastric cancer was analyzed.Correlations of the prognosis of gastric cancer patients with EpCAM and Claudin-18 expression were analyzed using the Cox proportional hazards regression model.Results The positive expression rate of EpCAM was elevated with the increase in tumor size and the occurrence of distant metastasis(x2 =4.526 and 36.090,P=0.033 and 0.000).There were significant differences in Claudin-18 protein expression among different age,TNM stage,growth pattern,depth of invasion and distant metastasis patients(all P＜0.05).Cox regression model analysis showed that tumor size and distant metastasis were the main risk factors affecting the survival of patients with gastric cancer (RR =50.076 and 1.617,P =0.016 and 0.032),while levels of EpCAM and Claudin-18 were not independent risk factors (both P ＞ 0.05).Conclusions EpCAM and Claudin-18 are closely related to the invasiveness of gastric cancer,but abnormally high levels of EpCAM and Claudin-18 are not independent risk factors for the prognosis of gastric cancer patients.

Novel mutations of ITGB2 induced leukocyte adhesion defect type 1 / 中华儿科杂志

Objective@#To investigate the pathogenic mechanism of two novel ITGB2 mutations in leukocyte adhesion defect type 1 (LAD1).@*Methods@#The clinical history and blood sample of an 11 years old patient admitted to Affiliated Hospital of Qingdao University in August 2014 were collected. Expression of CD18 (encoded by ITGB2) was analyzed by flow cytometry. Novel ITGB2 mutations were identified by next-generation sequencing technology and confirmed by Sanger sequencing. The functional effect of ITGB2 mutations was detected by PolyPhen2. Expression vectors of both wild type and mutant ITGB2 were constructed and transfected into mammalian cells for analysis of protein stability and subcellular location.@*Results@#The symptoms of the patient (recurrent infections, lowered alveolar ridge and hypodontia) supported the diagnosis of LAD1. Expression of CD18 on the leukocytes was significantly decreased (0.2%) compared with the control samples from the parents (paternal: 99.0%; maternal: 99.1%). The patient was identified to be compound heterozygous for ITBG2 c.954del G (novel mutation) and c.1802C>A (paternal originated). ITGB2 c.954 del G was confirmed to be a harmful frameshift mutation; ITGB2 c.1802C>A was also predicted to be harmful. In terms of protein stability. There was no significant difference between mutant D18 and wild type. However, subcellular location analysis showed the mutant D18 could not locate on cell membrane.@*Conclusion@#The compound heterozygous of ITGB2 mutations (c.954del G and c.1802C>A) decreases the expression and impairs the location of CD18 on leukocytes, which leads to LAD1.

Effects of positive end expiratory pressure ventilation on endothelial function during general anesthesia in patients with obstructive sleep apnea syndrome patient / 临床麻醉学杂志

Objective To observe the effect of intraoperative 5 cm H2O positive end expiratory pressure on vascular endothelial function in patients with uvulopalatopharynplasty (UPPP ). Methods Forty patients with obstructive sleep apnea-hypopnea syndrome (OSAHS)scheduled for UPPP were selected,including 25 males and 15 females,fully met the following conditions as age<60 years,BMI<30 kg/m2and ASA physical status Ⅰ or Ⅱ.Patients were divided into two groups, 20 in each group using random number table method.The observation group was given the intermit-tent positive pressure ventilation (IPPV)with 5 cm H2O PEEP,while the controls group were given IPPV.3 ml of arterial blood was drawn at the time of 5 min of pure oxygen Inhalation (T0),intuba-tion (T1),extubation (T2),and 20 min after extubation (T3).Vascular endothelium expansion fac-tors such as nitric oxide (NO),endothelin (ET),and soluble cell adhesion molecule (CAMs)were detected by ELISA.Results There was no significant difference in plasma ET concentrations between the two groups at different time points.Plasma NO concentration in the observation group was signif-icantly higher than that in the control group at T2and T3(P<0.05).Compared with T0,the concen-trations of CAMs in the control groups from T1to T3,and in the observation group at T2and T3in-creased significantly (P<0.05).In the perioperative period,the plasma CAMs of the control group increased along with the prolongation of the operation time,but the plasma CAMs concentrations in the observation group decreased in the same observation time (P<0.05).Conclusion Low level of PEEP 5 cm H2O may improve endothelial function in general anesthesia patients with OSAHS.

Expression of tumor stem cell marker EpCAM in patients undergoing liver transplantation for hepatocellular carcinoma and its relationship with tumor recurrence and metastasis / 中华普通外科杂志

Objective To investigate the expression of EpCAM (epithelial cell adhesion molecule) in patients undergoing liver transplantation for hepatocellular carcinoma (HCC),and to explore the relationship between EpCAM expression level and HCC recurrence.Methods 83 HCC tissue samples were collected and analyzed retrospectively.EpCAM was detected by immunohistochemistry staining and the correlation between EpCAM and clinicopathological features,prognosis and recurrence were analyzed retrospectively from patients undergoing liver transplantation in Peking University People's Hospital from 2000 to 2010.Results Log-rank univariate survival analysis showed that the 5-year overall survival (41.2％ vs.73.3％,x2 =4.935,P =0.026) and 5-year disease free survival (41.2％ vs.73.3％,x2 =4.634,P =0.031)of HCC patients with high EpCAM expression level was significantly lower than that with low expression level of EpCAM.COX multivariate survival analysis showed patients with high EpCAM expression had a higher risk of recurrence(HR =2.860,95％ CI:1.012-8.083) and death (HR =2.909,95％ CI:1.030-8.217)after liver transplantation than those with low EpCAM expression,which was an independent predictor of 5-year overall survival and 5-year disease free survival recurrence (P =0.044).Furthermore,EpCAM expression level was highly related to tumor distant metastasis (P =0.01).Conclusion There was positive relation between high expression of EpCAM and high HCC recurrence after liver transplantation,suggesting that EpCAM can be a predictor for HCC recurrence and long-term survival of patients with HCC after transplantation.

Expression of E-cadherin, Slug and NCAM and its relationship to tumor invasiveness in patients with acromegaly

Pituitary adenomas account for 10-15% of primary intracranial tumors. Growth hormone (GH)-secreting adenomas account for 13% of all pituitary adenomas and cause acromegaly. These tumors can be aggressive, invade surrounding structures and are highly recurrent. The objective of this study was to evaluate E-cadherin, Slug and neural cell adhesion molecule (NCAM) expression in GH-secreting pituitary adenomas and its relationship to tumor invasiveness. A cross-sectional study of patients who underwent hypophysectomy due to GH-secreting pituitary adenoma from April 2007 to December 2014 was carried out. The medical records were reviewed to collect clinical data. Immediately after surgery, tumor samples were frozen in liquid nitrogen and stored in a biofreezer at -80°C for assessment of E-cadherin 1 (CDH1), SLUG (SNAI2), and NCAM (NCAM1) by real-time PCR. The samples were fixed in formalin and embedded in paraffin for immunohistochemical analysis of E-cadherin and NCAM. Thirty-five patients with acromegaly were included in the study. Of these, 65.7% had invasive tumors. Immunohistochemically, E-cadherin was expressed in 96.7% of patients, and NCAM in 80% of patients. There was no statistically significant relationship between tumor grade or invasiveness and immunohistochemical expression of these markers. Regarding gene expression, 50% of cases expressed CDH1, none expressed SNAI2, and 53.3% expressed NCAM1. There was no statistically significant relationship between tumor grade or invasiveness and gene expression of CDH1, SNAI2, and NCAM1. The absence of Slug overexpression and of E-cadherin and NCAM suppression suggests that expression of these markers is not associated with tumor invasiveness in GH-secreting pituitary adenomas.

A new understanding of the pathogenesis of nonalcoholic fatty liver disease / 临床肝胆病杂志

The incidence rate of nonalcoholic fatty liver disease (NAFLD) has been increasing in China in recent years and has reached 11％-15％.At present,the multiple-hit hypothesis is considered the main pathogenesis of NAFLD,yet the specific pathogenesis remains unknown.This article elaborates on the roles of carcinoembryonic antigen-related cell adhesion molecule 1 highly expressed in the liver,vitamin D/vitamin D receptor axis,and psychological factors in the development and progression of NAFLD,in order to provide new directions for the research on the pathogenesis of NAFLD in future.

Expressions of ICAM-1,VCAM-1 and I-FABP in Lupus Enteropathy in Mice / 胃肠病学

Background:The prognosis of systemic lupus erythematosus complicated with lupus enteropathy is poor. At present, studies on pathogenesis of lupus enteropathy are rare. Aims:To investigate the expressions of intercellular adhesion molecule-1 (ICAM-1),vascular cell adhesion molecule-1 (VCAM-1)and intestinal fatty acid binding protein (I-FABP) in lupus enteropathy in mice. Methods:Twenty MRL/ lpr lupus mice were randomly divided into two groups:lupus enteropathy group and control group. Lupus enteropathy model was established by administration with TNBS enema. Histological score was assessed,expressions of ICAM-1,VCAM-1 and I-FABP were determined by immunohistochemistry, and correlations with histological score were analyzed. Results:Compared with control group,histological score was significantly increased (8. 1 ± 5. 8 vs. 0. 8 ± 0. 5,P = 0. 000),expressions of ICAM-1 (9. 4% ± 2. 1% vs. 6. 2% ± 1. 1%),VCAM-1 (15. 1% ± 2. 1% vs. 12. 2% ± 1. 9%)and I-FABP (17. 5% ± 2. 5% vs. 6. 1% ± 0. 9%)were significantly increased (P < 0. 05)in lupus enteropathy group. Expressions of ICAM-1,VCAM-1 and I-FABP in colon tissue in lupus enteropathy group were positively correlated with histological score (r = 0. 870,P = 0. 010;r = 0. 881,P =0. 010;r = 1. 000,P = 0. 000). Conclusions:ICAM-1,VCAM-1 and I-FABP may be associated with pathogenesis of lupus enteropathy.

Analysis on the relationship between plasma adhesion molecules, free amino acids and ovarian cancer / 中国医师杂志

Objective To analyze and study the relationship between plasma adhesion molecules,free amino acids and ovarian cancer.Methods A total of 67 patients with ovarian cancer in our hospital during the time of March 2015 to May 2016 were selected as the observation group,and 67 healthy women at the same time were selected as the control group.The plasma adhesion molecules and free amino acids levels of two groups were detected and compared,The detection levels of observation group with different stages and degree of differentiation of ovarian cancers were compared.The relationship between plasma adhesion molecules,free amino acids and ovarian cancer were analyzed by the Logistic analysis.Results The plasma adhesion molecules levels of observation group were all higher than those of control group (P ＜ 0.05),the plasma free amino acids levels were all lower than those of control group (P ＜ 0.05),and the detection levels of observation group with different stages and degree of differentiation of ovarian cancer plasma adhesion molecules and free amino acid levels had significant differences (P ＜ 0.05).The Logistic analysis showed that the plasma adhesion molecules and free amino acids had close relationship to the ovarian cancer (all P ＜ 0.05).Conclusions The plasma adhesion molecules and free amino acids of the patients with ovarian cancer show abnormal expression state,and the expression levels of patients with different stages and degree of differentiation of ovarian cancer have certain differences,so the detection value of those indexes in the patients with ovarian cancer is higher.

Changes in expression of neuroligin1 in excitatory postsynaptic membrane of spinal dorsal horn in a rat model of incisional pain / 中华麻醉学杂志

Objective To evaluate the changes in the expression of neuroligin1 in excitatory postsynaptic membrane of the spinal dorsal horn in a rat model of inc isional pain.Methods Forty-eight pathogen-free healthy adult male Sprague-Dawley rats,aged 6-8 weeks,weighing 280-320 g,were divided into control group (group C,n =12) and incisional pain group (group Ⅰ,n=36) using a random number table.A1 cm long incision was made in the plantar surface of the right hindpaw in group Ⅰ.Cumulative pain score (CPS) was assessed and mechanical paw withdrawal threshold to von Frey stimuli was measured at 3 hand 1 and 3 days after operation (T1,2,3).The animals were then sacrificed and their lumbar segments (L3-6) of the spinal cord were removed for detection of the expression of neuroligin1,postsynaptic density-95 protein (PSD-95),glutamate receptor 1 (GluR1) and GluR2 in the postsynaptic membrane of spinal dorsal horn (by Western blot) and co-expression of neuroligin1 with PSD-95 in spinal dorsal horn (by co-immuno-precipitation).Results Compared with group C,CPS was significantly increased and mechanical paw withdrawal threshold was decreased at T1-3,and the expression of neuroligin1 and GluR1 in the postsynaptic membrane of spinal dorsal horn at T1,2 and co-expression of neuroligin1 with PSD-95 at T1 were up-regulated in group Ⅰ (P＜0.01 or 0.05).Conclusion The development and maintenance of incisional pain is related to the signaling pathway regulated by neuroligin1 in excitatory postsynaptic membrane of the spinal dorsal horn of rats.

Vascular Cell Adhesion Molecule 1, Intercellular Adhesion Molecule 1, and Cluster of Differentiation 146 Levels in Patients with Type 2 Diabetes with Complications

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a multisystemic, chronic disease accompanied by microvascular complications involving various complicated mechanisms. Intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and cluster of differentiation-146 (CD146) are mainly expressed by endothelial cells, and facilitate the adhesion and transmigration of immune cells, leading to inflammation. In the present study, we evaluated the levels of soluble adhesion molecules in patients with microvascular complications of T2DM. METHODS: Serum and whole blood samples were collected from 58 T2DM patients with microvascular complications and 20 age-matched healthy subjects. Levels of soluble ICAM-1 (sICAM-1) and soluble VCAM-1 (sVCAM-1) were assessed using enzyme-linked immunosorbent assay, while flow cytometry was used to determine CD146 levels. RESULTS: Serum sICAM-1 levels were lower in T2DM patients with microvascular complications than in healthy controls (P<0.05). No significant differences were found in sVCAM-1 and CD146 levels between the study and the control group. Although patients were subdivided into groups according to the type of microvascular complications that they experienced, cell adhesion molecule levels were not correlated with the complication type. CONCLUSION: In the study group, most of the patients were on insulin therapy (76%), and 95% of them were receiving angiotensin-converting enzyme (ACE)-inhibitor agents. Insulin and ACE-inhibitors have been shown to decrease soluble adhesion molecule levels via various mechanisms, so we suggest that the decreased or unchanged levels of soluble forms of cellular adhesion molecules in our study group may have resulted from insulin and ACE-inhibitor therapy, as well as tissue-localized inflammation in patients with T2DM.

Usefulness of End-to-Side Bridging Anastomosis of Sural Nerve to Tibial Nerve: An Experimental Research

OBJECTIVE: Repair of sensorial nerve defect is an important issue on peripheric nerve surgery. The aim of the present study was to determine the effects of sensory-motor nerve bridging on the denervated dermatomal area, in rats with sensory nerve defects, using a neural cell adhesion molecule (NCAM). METHODS: We compared the efficacy of end-to-side (ETS) coaptation of the tibial nerve for sural nerve defect repair, in 32 Sprague-Dawley rats. Rats were assigned to 1 of 4 groups: group A was the sham operated group, group B rats had sural nerves sectioned and buried in neighboring muscles, group C experienced nerve sectioning and end-to-end (ETE) anastomosis, and group D had sural nerves sectioned and ETS anastomosis was performed using atibial nerve bridge. Neurological evaluation included the skin pinch test and histological evaluation was performed by assessing NCAM expression in nerve terminals. RESULTS: Rats in the denervated group yielded negative results for the skin pinch tests, while animals in the surgical intervention groups (group C and D) demonstrated positive results. As predicted, there were no positively stained skin specimens in the denervated group (group B); however, the surgery groups demonstrated significant staining. NCAM expression was also significantly higher in the surgery groups. However, the mean NCAM values were not significantly different between group C and group D. CONCLUSION: Previous research indicates that ETE nerve repair is the gold standard for peripheral nerve defect repair. However, ETS repair is an effective alternative method in cases of sensorial nerve defect when ETE repair is not possible.

Adrenomedullin promotes cell-cell contact formation of podocytes through regulating Rho GTPases / 中华肾脏病杂志

Objective To investigate the regulatory effect of adrenomedullin (AM) on the cell-cell contact formation of podocytes and the possible mechanism.Methods Podocytes were treated with AM (10-7 mol/L),AM combined with a PKA inhibitor H89 (10-4 mol/L),and forskolin (10-5 mol/L) as positive control respectively for 12 hours.Immunofluorescent staining was applied to observe the distribution of cell adhesion molecules and actin-associated proteins.Western blotting assay was used to assess their protein levels.Rho GTPases activity was analyzed by GST-pull down assay and their protein levels were tested by Western blotting.Results AM induced the redistribution of adhesion molecules,actin-associated proteins as well as the F-actin at cell-cell contacts between podocytes.This effect was similar to that of forskolin and could be blocked by H89.The levels of those proteins did not change significantly (P ＞ 0.05).AM up-regulated the activities of RhoA,Rac1 and Cdc42 (P ＜ 0.05),which were partially blocked by H89.The protein levels of Rho GTPases showed no difference compared with the control (P ＞ 0.05).Conclusions AM may promote cell-cell contact formation of podocytes,probably through enhancing the activity of Rho GTPases and then resulting in the redistribution of adhesion molecules,actin-associated proteins and F-actin,which is partially mediated through cAMP-PKA signaling pathway.