A transient ischemic attack (TIA) can cause reversible and delayed impairment of cognition, but the specific mechanisms are still unclear. Annexin a1 (ANXA1) is a phospholipid-binding protein. Here, we confirmed that cognition and hippocampal synapses were impaired in TIA-treated mice, and this could be rescued by multiple mild stimulations (MMS). TIA promoted the interaction of ANXA1 and CX3CR1, increased the membrane distribution of CX3CR1 in microglia, and thus enhanced the CX3CR1 and CX3CL1 interaction. These phenomena induced by TIA could be reversed by MMS. Meanwhile, the CX3CR1 membrane distribution and CX3CR1-CX3CL1 interaction were upregulated in primary cultured microglia overexpressing ANXA1, and the spine density was significantly reduced in co-cultured microglia overexpressing ANXA1 and neurons. Moreover, ANXA1 overexpression in microglia abolished the protection of MMS after TIA. Collectively, our study provides a potential strategy for treating the delayed synaptic injury caused by TIA.
Animals ; Annexin A1/metabolism* ; CX3C Chemokine Receptor 1/metabolism* ; Chemokine CX3CL1 ; Cognition ; Dendritic Spines/metabolism* ; Ischemic Attack, Transient ; Mice ; Microglia/metabolism*

OBJECTIVES: To investigate the expression changes of annexin A1 （ANXA1） during the process of skin incision healing, and to explore its expression and function during skin injury repair. METHODS: The skin injury model of mice was prepared, and skin tissues of the controls and the injured group at 6 h, 12 h, 1 d, 3 d, 5 d, 7 d, 10 d and 14 d after injuries were taken. The morphological changes of the wound were observed by hematoxylin-eosin （HE） staining, and the expression of ANXA1 was detected by immunohistochemistry （IHC） and Western blotting. RESULTS: HE staining showed normal healing of skin wounds. IHC results revealed that ANXA1 was expressed in the epidermis, hair follicle, sebaceous gland and vascular endothelium. In the injured group, the expression of ANXA1 was enhanced in epidermis and skin appendages around the wound 6-12 h after injury, and ANXA1 was also highly expressed in neutrophils and a small number of mononuclear cells. ANXA1 was mainly positively expressed in monocytes, neovascular endothelial cells and fibroblasts, and small amount of fibroblasts at 1-3 d, 5-10 d, and 14 d after injury, respectively. Western blotting showed that, compared with the controls, the expression of ANXA1 was significantly increased at 6 h after injury, peaked at 1 d, and then decreased gradually in the injured group. CONCLUSIONS ANXA1 may be involved in the regulation of skin damage repair, with time-dependent expression during skin wound healing, and thus is expected to be a biological marker for inferring the wound formation time.
Animals ; Annexin A1/metabolism* ; Fibroblasts ; Mice ; Neutrophils ; Skin ; Wound Healing

OBJECTIVE: To investigate the effect Pinggan Qianyang recipe on expression of Tpx, HSP27 and ANXA1 in the hypothalamus of spontaneously hypertensive rats (SHRs) with the hyperactivity of liver-YANG syndrome. METHODS: A total of 30 SHRs were subjected to administration of Aconiti Praeparatae Decoction to establish the model of SHR with liver-YANG hyperactivity first, then they were randomly divided into three groups: the control group, the model group and the treatment group (n=10 per group). A total of 10 SD rats were served as the normal group. The rats in control group and treatment group were given Enalapril plus Pinggan Qianyang recipe for four weeks. The change of behavior and blood pressure of rats were monitored. RT-PCR and Western-blot were performed to detect the expression of Tpx II, HSP27 and ANXA1 mRNA and protein in the hypothalamus, respectively. RESULTS: Compared with the normal SD rats, the heart rate, blood pressure and grade of irritability were significantly increased while rotation endurance time was dramatically reduced in the SHR model with liver-YANG hyperactivity (P<0.01), these changes were reversed by the application of Enalapril plus Pinggan Qianyang recipe. Compared with the normal SD rats, the protein and mRNA expression of Tpx II and ANXA1 in the model group were significantly upregulated (P<0.01) while the HSP27 was significantly downregulated (P<0.01). Compared with the model group, the protein and mRNA expression of Tpx II and ANXA1 in the control group or treatment group were significantly decreased (P<0.05 or P<0.01) while HSP27 was significantly increased (P<0.05 or P<0.01). Compared with the control group, the expression of Tpx II and ANXA1 protein in treatment group were significantly reduced (P<0.05 or P<0.01). CONCLUSION Pinggan Qianyang recipe can improve the blood pressure and behavior in SHRs with hyperactivity of Liver-YANG syndrome, which might be related to the regulation of Tpx, HSP27 and ANXA1 expression in hypothalamuses.
Animals ; Annexin A1 ; metabolism ; Blood Pressure ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Enalapril ; pharmacology ; HSP27 Heat-Shock Proteins ; metabolism ; Hypothalamus ; drug effects ; metabolism ; Liver ; physiopathology ; Rats ; Rats, Inbred SHR

OBJECTIVE: To investigate the correlation of Annexin A1 (ANXA1) expression with paclitaxel response and clinicopathological features of ovarian carcinoma. METHODS: The expression levels of ANXA1 in ovarian carcinoma SKOV3/Taxol-25 and SKOV3 cell lines were detected by Western blot and real time-PCR. The expression of ANXA1 protein in 42 specimens of ovarian carcinoma was examined by immunhistochemistry. The correlation of ANXA1 expression with paclitaxel response and clinicopathological features of ovarian carcinoma was analyzed. RESULTS: The expression level of ANXA1 was significantly lower in SKOV3/Taxol-25 cell line than that in SKOV3 cell line (P<0.05). The positive specimens of ANXA1 expression in paclitaxel-resistant tissues (14/20) were significantly lower than those in the sensitive ones (21/22, P<0.05), and there was also a significant difference between the mild and the strong positive specimens (P<0.01). The expression of ANXA1 protein showed no correlation with the type of mophology and histological grade of ovarian cancer (P>0.05), but it was correlated with the clinical stage(P<0.05). CONCLUSION ANXA1 expression is downregulated in paclitaxel-resistant ovarian carcinoma, which might be a valuable predictor for paclitaxel susceptibility of ovarian carcinoma.
Annexin A1 ; metabolism ; Blotting, Western ; Down-Regulation ; Drug Resistance, Neoplasm ; Female ; Humans ; Ovarian Neoplasms ; drug therapy ; metabolism ; Paclitaxel ; pharmacology

Annexin A1 (ANXA1) is a kind of endogenous scaffold protein. Previous research showed that ANXA1 could increase markedly with multiple increase of drug resistance in K562/imatinib cell lines in vitro. Here the stable transfection cell strains K562-pEGFP-N1 which was the native control and K562-pEGFP-N1-ANXA1 which can stably express ANXA1 were established using the Lipofectamine 2000 in order to find whether ANXA1 involved in the drug resistance. Cell growth inhibition experiment via MTT and cell proliferation experiment via MTS showed that K562-pEGFP-N1-ANXA1 cell strain was more sensitive to imatinib than the K562-pEGFP-N1 cell strain, and however the ability of proliferation of K562-pEGFP-N1-ANXA1 cell strain did not change compared with the negative control. Western blotting results showed that the expression of proteins in Annexin family did not change; drug resistance proteins, Bcr-Abl/p-Bcr-Abl (Tyr245), Src family kinase for example, did not change; proteins related with cell proliferation and cell cycle, such as ERK1/2MAPK, p-38MAPK, CDK1 and Wee 1, did not change either in the K562-pEGFP-N1-ANXA1 cell strain compared with the negative control. The co-immunoprecipitation result showed that the interaction between ANXA1 and beta-actin in the K562-pEGFP-N1-ANXA1 cell strain increased markedly. The deduction was that ANXA1 may make the K562-pEGFP-N1-ANXA1 cell strain more sensitive to imatinib due to the increased uptake of imatinib via the increase of ANXA1 and the interaction between ANXA1 and beta-actin in the K562-pEGFP-N1-ANXA1 cell strain in vitro.
Actins ; metabolism ; Annexin A1 ; genetics ; metabolism ; Antineoplastic Agents ; pharmacology ; Cell Proliferation ; drug effects ; Drug Resistance, Neoplasm ; Fusion Proteins, bcr-abl ; metabolism ; Humans ; Imatinib Mesylate ; pharmacology ; Immunoprecipitation ; K562 Cells ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Transfection ; src-Family Kinases ; metabolism

OBJECTIVETo investigate the diagnostic significance of D2-40 and annexin-1 in the ependymal tumors.

METHODSTo analyses the expression of D2-40, annexin-1, EMA and Ki-67 by immunohistochemistry in 52 cases of ependymal tumors (48 cases of ependymomas, 4 cases of choroid plexus papilloma) from Xuanwu Hospital from 2005 to 2009. Ten cases of corresponding normal brain tissue were also obtained as control.

RESULTSThirty-two of forty-eight (66.7%) cases of ependymomas were positive for D2-40. "Dot-like" and "ring-like" structures were commonly observed in ependymomas (55.3%, 21 of 38 cases) and anaplastic ependymomas (5 of 6 cases) with D2-40 staining. There was no difference in the expression between D2-40 and Ki-67 (r(s) = -0.013, P = 0.931). For annexin-1, 87.5% (42 of 48 cases) of the ependymomas were positive. The specific "granular structures" and cilium were observed in ependymomas (1 of 4 cases of myxopapillary ependymomas and 11 of 38 cases of ependymomas respectively) for annexin-1. The difference in expression between annexin-1 and Ki-67 was statistically significant (r(s) = -0.405, P = 0.005). D2-40 in combination of EMA and annexin-1 increased the positive rate to 100% in ependymomas. Choroid plexus papillomas were all positive for D2-40 and annexin-1. The control tissue was negative for D2-40 but positive for annexin-1 in the capillaries.

CONCLUSIONSThe specific structures are valuable in diagnosing of ependymal-genetic tumors, and are highlighted by D2-40 and annexin-1. D2-40 in combination of EMA and annexin-1 is a useful diagnostic marker for ependymal tumors.

Adolescent ; Adult ; Annexin A1 ; metabolism ; Biomarkers, Tumor ; metabolism ; Brain Neoplasms ; diagnosis ; metabolism ; pathology ; Child ; Child, Preschool ; Ependymoma ; diagnosis ; metabolism ; pathology ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; metabolism ; Male ; Membrane Glycoproteins ; metabolism ; Middle Aged ; Mucin-1 ; metabolism ; Papilloma, Choroid Plexus ; diagnosis ; metabolism ; pathology ; Young Adult

OBJECTIVETo study the expression levels of ANXA1 and ANXA2 and elucidate their clinicopathological significance in adenocarcinoma, peritumoral tissues, adenomatous polyp and chronic cholecystitis of gallbladder.

METHODSEnVision(TM) immunohistochemical staining was used to detect the expression of ANXA1 and ANXA2 in paraffin-embedded tissue sections from resected specimens of adenocarcinoma (n = 108), peritumoral tissue (n = 46), adenomatous polyp (n = 15) and chronic cholecystitis (n = 35).

RESULTSThe positive rates and scores of ANXA1 and ANXA2 were significantly higher in adenocarcinoma (59.3%, 56.5%; 3.2 ± 0.9, 3.4 ± 0.8) than those in peritumoral tissues (34.8%, 1.1 ± 0.8, P < 0.01; 30.4%, 1.0 ± 0.8, P < 0.01), adenomatous polyp (26.7%, 0.9 ± 0.7, P < 0.05 or P < 0.01; 26.7%, 0.9 ± 0.8, P < 0.05 or P < 0.01) and chronic cholecystitis (17.1%, 0.7 ± 0.9, P < 0.01; 20.0%, 0.8 ± 0.8, P < 0.01). The benign lesions with positive ANXA1 and/or ANXA2 expression showed mild to severe atypical hyperplasia of the gallbladder epithelium. The positive rates of ANXA1 and/or ANXA2 were significantly lower in the well-differentiated adenocarcinoma, in a maximal diameter of < 2 cm, with no metastasis to lymph nodes and no invasion to surrounding tissues than those in the moderately or poorly-differentiated adenocarcinoma, in a maximal diameter of ≥ 2 cm, with metastasis to lymph nodes and invasion in surrounding tissues (P < 0.05 or P < 0.01). A high consistence was found between the expression levels of ANXA1 and ANXA2 (χ(2) = 67.84, P < 0.01), and a close positive correlation between the scores of ANXA1 and ANXA2 (r = 0.78, P < 0.01) in gallbladder adenocarcinoma. Kaplan-Meier analysis and multivariate Cox regression analysis showed that ANXA1 or ANXA2 was not an independent prognostic predictor in gallbladder adenocarcinoma.

CONCLUSIONThe expression levels of ANXA1 and/or ANXA2 may be important biological markers in the carcinogenesis, progression and biological behaviors of gallbladder adenocarcinoma.

Adenocarcinoma ; metabolism ; pathology ; surgery ; Adenocarcinoma, Mucinous ; metabolism ; pathology ; surgery ; Adenomatous Polyps ; metabolism ; pathology ; Adult ; Aged ; Annexin A1 ; metabolism ; Annexin A2 ; metabolism ; Cholecystectomy ; methods ; Cholecystitis ; metabolism ; pathology ; Female ; Gallbladder ; metabolism ; pathology ; Gallbladder Neoplasms ; metabolism ; pathology ; surgery ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Proportional Hazards Models ; Survival Rate

OBJECTIVETo identify and compare the expression profiles of differential proteins between chronic phase and blast crisis in chronic myeloid leukemia (CML) by proteomic analysis, and screen the proteins related to blast crisis.

METHODSThe total cellular proteins from the bone marrow cells at chronic phase (CP) and blast crisis (BC) in CML were separated by two-dimensional polyacrylamide gel electrophoresis (2-DE) and analyzed with ImageMaster 5.0 software to screen the differential protein spots. Differential protein spots were identified by mass spectrometry for peptide mass fingerprint in combination with database searching from SWISS-PROT. Then 3 protein spots were selected to verify at protein and mRNA levels by Western blot and semi-quantitative RT-PCR, separately.

RESULTSComparing gel pages from CML-CP and CML-BC, the expression of 13 protein spots decreased and 25 protein spots increased significantly in CML-BC. Twenty differential protein spots were identified by mass spectrometry and 15 were successfully determined. The results of Western blotting were similar to those of 2-DE and showed a high expression of hnRNPK, annexin A1 and RhoA. Semi-quantitative RT-PCR analysis showed that there was no correlation between the protein expression changes and mRNA levels of hnRNPK, annexin A1 and RhoA.

CONCLUSIONA group of proteins associated with blast crisis are obtained and the results may provide clues for further research to elucidate the role of these proteins in CML-BC carcinogenesis and to develop potential associated biomarkers.

Adult ; Aged ; Annexin A1 ; genetics ; metabolism ; Blast Crisis ; genetics ; metabolism ; Female ; Gene Expression Profiling ; Heterogeneous-Nuclear Ribonucleoprotein K ; Humans ; Leukemia, Myeloid, Chronic-Phase ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Proteomics ; methods ; RNA, Messenger ; metabolism ; Ribonucleoproteins ; genetics ; metabolism ; Young Adult ; rhoA GTP-Binding Protein ; genetics ; metabolism

OBJECTIVETo investigate the clinicopathologic features, diagnosis, differential diagnosis and the prognosis of hairy cell leukemia (HCL).

METHODSFifteen splenectomy specimens of HCL patients were investigated retrospectively using HE and immunohistochemistry in correlation with the follow-up information.

RESULTS(1) The male to female ratio was 2.75:1, age ranged from 36 to 68 years with a median of 47 years. The most consistent clinical feature at presentation was marked splenomegaly (100%). Other symptoms included anemia (80.0%), thrombocytopenia (60.0%), leucocytosis (53.3%), pancytopenia (20.0%) and the absence of B-symptom. (2) The proportion of hairy cells was (14.6 +/- 7.2)% in periphery blood and (47.3 +/- 23.8)% in bone marrow. The positive rate of TRAP assay was 62.5% in bone marrow; 85.7% for TPA test and the detection rate for RLC was 25% by transmission electric microscopy. The frequency of bone marrow involvement was 100%. (3) The average weight of 15 spleens was (3012 +/- 1974) g. The size of 6 spleens ranged from 16 cm x 10 cm x 5 cm to 32 cm x 20 cm x 14 cm. The white pulp of spleen showed a characteristic atrophy feature or even absent due to leukemic infiltration, predominantly involving the red pulp with some sinusoidal pattern. "Blood pool" change was an infrequent feature (3/15 cases). The nuclei of leukemic cells were round (13 cases) or bean-shaped (2 cases), nucleoli inconspicuous or disappeared. The abundant cytoplasm and prominent cell border resulted in a "fried egg" appearance. By immunohistochemistry, leukemic cells were positive for CD45RA, CD20, PAX-5, CD25, CD11c, Annexin A1 and cyclinD1, but negative for CD3 and CD43. (4) 13 cases (86.7%) have been followed-up and all are alive. Among them, 9 cases are living well more than 5 years and 7 more than 10 years.

CONCLUSIONSSplenomegaly is frequently the first manifestation of patients with HCL and occurred predominantly in the middle to elderly adults. Definite diagnosis of HCL requires a combined histological and immunohistochemical assessment of the splenectomy specimen, bone marrow biopsy and aspirate.

Adult ; Aged ; Annexin A1 ; metabolism ; Antigens, CD20 ; metabolism ; CD11c Antigen ; metabolism ; CD79 Antigens ; metabolism ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Ki-67 Antigen ; metabolism ; Leukemia, Hairy Cell ; metabolism ; pathology ; surgery ; Leukemia, Lymphocytic, Chronic, B-Cell ; metabolism ; pathology ; Leukemia, Prolymphocytic ; metabolism ; pathology ; Leukocyte Common Antigens ; metabolism ; Lymphoma, B-Cell, Marginal Zone ; metabolism ; pathology ; Lymphoma, Follicular ; metabolism ; pathology ; Lymphoma, Mantle-Cell ; metabolism ; pathology ; Male ; Middle Aged ; Retrospective Studies ; Spleen ; pathology ; Splenectomy ; Survival Rate

BACKGROUNDAnnexin-1 was identified as an endometriosis-related protein by comparative proteomics in previous study. As an endogenous anti-inflammatory mediator, Annexin-1 has been shown to regulate the immune response, cell proliferation and apoptosis. To investigate whether Annexin-1 is involved in the pathogenesis of endometriosis, we examined the expression of Annexin-1 in eutopic endometrium of women with or without endometriosis, and detected its expression in peritoneal fluids of those with endometriosis.

METHODSEutopic endometrium samples from twenty-five women with endometriosis and those from sixteen age-matched women without endometriosis were collected. Peritoneal fluids were obtained from ten patients with endometriosis. The expression of Annexin-1 protein in eutopic endometrium was detected by immunohistochemistry and Western blotting, and mRNA detected by real-time PCR. Annexin-1 protein in the peritoneal fluids was detected by Western blotting.

RESULTSAnnexin-1 mRNA and protein were overexpressed in eutopic endometrium of endometriosis without significant differences between the proliferative and secretory phase. Immunohistochemistry showed that Annexin-1 protein was expressed mainly in endometrial glandular cells throughout the menstrual cycle. Annexin-1 protein was detected in the peritoneal fluids of all the ten patients with endometriosis.

CONCLUSIONSAnnexin-1 is overexpressed in eutopic endometrium and presents in the peritoneal fluids of patients with endometriosis, and may play a role in the pathogenesis of endometriosis.

Adult ; Annexin A1 ; genetics ; metabolism ; Ascitic Fluid ; metabolism ; Blotting, Western ; Endometriosis ; genetics ; metabolism ; pathology ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Middle Aged ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction