Humans ; Nerve Tissue Proteins ; Epithelial-Mesenchymal Transition/genetics* ; Constriction, Pathologic ; Receptors, Immunologic ; Epithelial Cells/metabolism* ; Smad3 Protein/metabolism* ; Transforming Growth Factor beta1/metabolism*

OBJECTIVETo investigate the expressions and action mechanisms of nerve growth factor (NGF) receptors TrkA and p75NTR in the oncogenesis and progression of prostate cancer (PCa).

METHODSUsing immunohistochemistry, we detected the expressions of TrkA and p75NTR in 62 PCa and 35 benign prostatic hyperplasia (BPH) samples, and conducted statistical analysis on the basis of clinical data.

RESULTSIndependent-samples t-test showed that, along with poorer tissue differentiation or higher clinical stage of PCa, the expression of TrkA was significantly up-regulated, that of p75NTR remarkably down-regulated, and the expression ratio of TrkA to p75NTR markedly increased. The TrkA/p75NTR ratio was 0.32 in the BPH, 0.52 in the PCa tissue with Gleason score of 6, 1.65 in the PCa tissue with Gleason score of 7, 5.75 in the PCa tissue with Gleason score ≥ 8, 0.89 in the clinical stage of pT2, 1.5 in pT3 a, 3.75 in pT3b, and 7.00 in pTxN1.

CONCLUSIONThe abnormally increased expression ratio of TrkA to p75NTR might be one of the essential features of malignant transformation of prostate cells. A higher TrkA/p75NTR expression ratio may be associated with a lower tissue differentiation, a higher clinical stage or Gleason score, and therefore a poorer prognosis.

Humans ; Immunohistochemistry ; Male ; Neoplasm Grading ; Neoplasm Staging ; Nerve Tissue Proteins ; metabolism ; Prognosis ; Prostatic Hyperplasia ; pathology ; Prostatic Neoplasms ; pathology ; Receptor, trkA ; metabolism ; Receptors, Nerve Growth Factor ; metabolism ; Up-Regulation

In the present study, we investigate the expression profile of the epidermal growth factor receptor family, which comprises EGFR/ErbB1, HER2/ErbB2, HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia (LP). The expression of four epidermal growth factor receptor (EGFR) family genes and their ligands were measured in LP tissues from 14 patients and compared with levels in 10 patients with oral lichen planus (OLP) and normal oral mucosa (NOM) from 14 healthy donors by real-time polymerase chain reaction (PCR) and immunohistochemistry. Synchronous mRNA coexpression of ErbB1, ErbB2, ErbB3 and ErbB4 was detected in LP lesions. Out of the receptors, only ErbB4 mRNA and protein was more highly expressed in LP compared with NOM tissues. These were strongly expressed by epithelial keratinocytes in LP lesions, as shown by immunohistochemistry. Regarding the ligands, the mRNA of Neuregulin2 and 4 were more highly expressed in OLP compared with NOM tissues. Therefore, enhanced ErbB4 on the keratinocytes and synchronous modulation of EGFR family genes may contribute to the pathogenesis and carcinogenesis of LP.
Adult ; Aged ; Amphiregulin ; Betacellulin ; EGF Family of Proteins ; Epidermal Growth Factor ; metabolism ; Epiregulin ; Female ; Gene Expression Profiling ; Glycoproteins ; metabolism ; Heparin ; metabolism ; Heparin-binding EGF-like Growth Factor ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Keratinocytes ; metabolism ; Leukoplakia, Oral ; metabolism ; Lichen Planus, Oral ; metabolism ; Ligands ; Male ; Middle Aged ; Mouth Mucosa ; metabolism ; Nerve Growth Factors ; Neuregulins ; metabolism ; RNA, Messenger ; metabolism ; Real-Time Polymerase Chain Reaction ; Receptor, Epidermal Growth Factor ; metabolism ; Receptor, ErbB-2 ; metabolism ; Receptor, ErbB-3 ; metabolism ; Receptor, ErbB-4 ; Receptors, Cell Surface ; metabolism ; Transforming Growth Factor alpha ; metabolism ; Up-Regulation ; physiology

OBJECTIVE: To study the expression of PCNA and LNGFr in olfactory epithelium of patients suffering from dysosmia caused by chronic sinusitis, and the function of LNGFr. METHOD: Forty-six patients undergoing FESS were chosen. Before operation, their olfactory functions were examined with CCCRC. According to their CCCRC scores, they were divided into three groups. Group A: Patients with chronic sinusitis and dysosmia 25 cases; Group B: Patients with chronic sinusitis and a normal olfactory function 10 cases; Group C: Patients with deviation of nasal septum and a normal olfactory function 11 cases. The expressions of PCNA and LNGFr were measured in olfactory mucosas of the three groups by immunohistochemistry. RESULT: In basal cells, the expression of PCNA and LNGFr in group A was higher than that in group B (P < 0.01). and in group C (P < 0.01). There was negative correlation between positive cells of PCNA and CCCRC score in basal cells of group A (r = -0.7441, P < 0.01); There was negative correlation between integral optical density of LNGFr and CCCRC score in basal cells of group A (r = -0.4407, P < 0.05). There was positive correlation between positive cells of PCNA and integral optical density of LNGFr in basal cells of group A (r = 0.5317, P < 0.01). CONCLUSION Basal cells proliferated dramatically in patients suffering from dysosmia caused by chronic sinusitis. The proliferating capacity of basal cells was related to up-regulation of LNGFr expression.
Chronic Disease ; Humans ; Immunohistochemistry ; Nerve Tissue Proteins ; metabolism ; Olfaction Disorders ; metabolism ; Olfactory Mucosa ; metabolism ; Proliferating Cell Nuclear Antigen ; metabolism ; Receptors, Nerve Growth Factor ; metabolism ; Sinusitis ; complications

The aim of this study was to detect the nerve growth factor (NGF) level in serum and NGF low affinity acceptor CD271 expression on bone marrow leukemic cells in acute B lymphoid leukemia (B-ALL) patients and to analyze their clinical significance. The NGF level in serum and CD271 expression on leukemic cells in bone marrow were detected by enzyme linked immunosorbent assay and flow cytometry in B-ALL patients respectively. The results indicated that compared with control group, the NGF level in serum of patient group significantly increased (t = 4.191, p < 0.05), but CD271 expression on leukemic cells in bone marrow decreased significantly (t = 4.898, p < 0.05). The complete remission (CR) rate of 25 B-ALL patients was 64% (16/25) after one course of CVAD chemotherapy. There were statistically significant differences of NGF level and CD271 expression in non-remission (NR) group and control group (t = 3.976, p < 0.05 vs t = 5.052, p < 0.05), but there were no statistically difference of NGF level and CD271 expression in CR group (t = 1.102, p > 0.05 vs t = 1.150, p > 0.05) as compared with control group. The CD271 expression before and after chemotherapy between CR and NR groups showed statistically significant differences (t = 3.889, p < 0.05; t = 3.751, p < 0.05 and t = 4.678, p < 0.05 respectively), but NGF level before and after chemotherapy showed no statistical difference between these 2 groups (t = 0.476, p > 0.05). 50% (8/16) patients relapsed during following up, and of their NGF level [(168.00 ± 61.66) pg/ml] and CD271 expression [(52.29 ± 13.00)%] showed the significantly differences, compared with those in control group (t = 5.284, p < 0.05 vs. t = 6.073, p < 0.05), but the NGF level [(81.13 ± 25.32) pg/ml] and CD271 expression [(78.45 ± 7.12)%] of other 8 patients showed no statistical difference as compared with control group (t = 1.228, p > 0.05 vs t = 1.144, p > 0.05). Compared with low NGF level and CD271 low expression groups, the survival time of B-ALL patients with high NGF level and CD271 expression was not changed significantly (p = 0.750 vs p = 0.170). It is concluded that the increased NGF level in serum and decreased CD271 expression on bone marrow leukemic cells in B-ALL patients are related with leukemia development and may be the useful indexes to evaluate curative effect and prognosis.
Adolescent ; Adult ; Aged ; Bone Marrow Cells ; metabolism ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Nerve Growth Factor ; blood ; Nerve Tissue Proteins ; metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; blood ; metabolism ; Receptors, Nerve Growth Factor ; metabolism ; Young Adult

OBJECTIVETo study the molecular mechanism of Zuogui Pill (ZGP) and Yougui Pill (YGP) on axonal regeneration in rats with experimental autoimmune encephalomyelitis (EAE).

METHODSEAE rat model was established by bilateral rear pedes subcutaneous injection of antigen made by mixing myelin basic protein (MBP) and complete Freud's adjuvant (CFA) in the volume ratio of 1:1. The pathological changes of axonal injury and regeneration in the brain and the spinal cord were observed on the 14th (the acute stage) and the 28th day (the remission stage) after modeling, with hematoxylin-eosin (HE) staining, silver stain, and immunohistochemical staining. The rats treated with prednisone acetate were taken as controls.

RESULTSObservation under the light microscope with HE staining showed a sleeve-like change in rats' cerebrospinal parenchyma with inflammatory cell infiltration around the small vessels and neuronic denaturation, while silver staining showed excessive tumefaction and abscission of axon, and immunohistochemical analysis showed decreasing of nerve growth factor (NGF) expression at the acute stage of EAE, which was even more remarkable at the remission stage, showing significant difference as compared with the normal control (P<0.05). And the expressions of Nogo A, an axon growth inhibitor, and its receptor (Nogo-66 receptor, Ng R) were significantly higher than those in the normal control at the acute stage (P<0.01). However, after the intervention of ZGP and YGP, the pathological changes and axon damage in rats' brain and spinal cord were much more alleviated, and the NGF expression was significantly higher than that in the model group at the acute stage (P<0.05). The expression of NGF was even stronger during the remission stage, and a better effect was shown by YGP. As for Nogo A and Ng R expressions, they were significantly lower than those in the model group at the acute stage (P<0.05), but a better effect was shown by ZGP.

CONCLUSIONSZGP and YGP can prevent axonal injury and promote the axonal regeneration in rats of EAE, and the possible mechanism is to increase the expression of NGF and reduce the expression of Nogo A and its receptor. However, some differences are observed between the two Chinese preparations in their acting times and points, which provides a certain basis for revealing the modern connotation of the Chinese medicine theory on tonifying Shen ()-yin and Shen-yang.

Animals ; Axons ; drug effects ; metabolism ; pathology ; physiology ; Brain ; drug effects ; metabolism ; pathology ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Encephalomyelitis, Autoimmune, Experimental ; drug therapy ; metabolism ; pathology ; GPI-Linked Proteins ; Male ; Myelin Proteins ; metabolism ; Nerve Growth Factor ; metabolism ; Nerve Regeneration ; drug effects ; Nogo Proteins ; Nogo Receptor 1 ; Rats ; Rats, Inbred Lew ; Receptors, Cell Surface ; Receptors, Peptide ; metabolism ; Research ; Signal Transduction ; drug effects ; Tablets

BACKGROUNDBy unbiased stereological methods, we have observed preferential dorsal root ganglion (DRG) B-cell loss in rodents after nerve injury, and caspase-3 activation and cell loss were related to the present of p75 receptor (p75(NTR)). We hypothesized that DRG B-cells express higher levels of pro-apoptotic proteins as compared to A-cells and the expressions of pro-apoptotic proteins can be reduced by depletion of p75(NTR). This study aimed to identify the p75(NTR) involved apoptotic pathway in DRG neurons after nerve injury.

METHODSThe p75(NTR) knockout mice (p75-/-) and wildtype Balb/C mice (p75+/+) were used in this study. The expressions of pro-apoptotic proteins, c-Jun-N-terminal kinase (JNK), c-jun and p38 in DRG were evaluated with immunohistochemistry 2 and 7 days following unilateral sciatic nerve transection. In addition, extra-cellular related kinase (ERK), a transducer of survival signals, was also tested with immunohistochemistry and Western blotting methods in these animal models.

RESULTSPhosphorylated JNK (P-JNK) and phosphorylated p38 (P-p38) were mainly located in small B-cells, whereas phosphorylated c-jun (P-c-jun) was located in both A- and B-cells. Phosphorylated ERK (P-ERK) was located in both B-cells and satellite cells. Axotomy dramatically increased the expressions of P-JNK and P-c-jun (paired t-test), with no influence on the expressions of P-p38 and P-ERK. Furthermore, the increase of P-JNK in p75+/+ mice 2 days after nerve axotomy was approximately 2.2-folds of that in p75-/- mice (P = 0.001, unpaired t-test).

CONCLUSIONp75(NTR)-dependent JNK-caspase-3 pathway is involved in DRG B-cell loss after nerve injury and JNK is not the unique upstream of c-jun activation.

Animals ; Apoptosis ; genetics ; physiology ; Axotomy ; adverse effects ; Blotting, Western ; Ganglia, Spinal ; cytology ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Neurons ; cytology ; metabolism ; Receptors, Nerve Growth Factor ; genetics ; metabolism ; Sciatic Nerve ; surgery

Neurotrophins protect neurons against excitotoxicity; however the signaling mechanisms for this protection remain to be fully elucidated. Here we report that activation of the phosphatidyl inositol 3 kinase (PI3K)/Akt pathway is critical for protection of hippocampal cells from staurosporine (STS) induced apoptosis, characterized by nuclear condensation and activation of the caspase cascade. Both nerve growth factor (NGF) and brain-derived growth factor (BDNF) prevent STS-induced apoptotic morphology and caspase-3 activity by upregulating phosphorylation of the tropomyosin receptor kinase (Trk) receptor. Inhibition of Trk receptor by K252a altered the neuroprotective effect of both NGF and BDNF whereas inhibition of the p75 neurotrophin receptor (p75NTR) had no effect. Impairment of the PI3K/Akt pathway or overexpression of dominant negative (DN)-Akt abolished the protective effect of both neurotrophins, while active Akt prevented cell death. Moreover, knockdown of Akt by si-RNA was able to block the survival effect of both NGF and BDNF. Thus, the survival action of NGF and BDNF against STS-induced neurotoxicity was mediated by the activation of PI3K/Akt signaling through the Trk receptor.
Animals ; Apoptosis/*drug effects ; Brain-Derived Neurotrophic Factor/*metabolism ; Cell Line ; Cell Survival/drug effects ; Cytoprotection/*drug effects ; Gene Knockdown Techniques ; Hippocampus/*cytology ; Nerve Growth Factor/*metabolism ; Neurons/*cytology/drug effects/metabolism ; PC12 Cells ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Receptors, Nerve Growth Factor/metabolism ; Signal Transduction/drug effects ; Staurosporine/*pharmacology

This study was purposed to detect the expressions of CD271, CD133 and CD34, and to analyze the correlation of CD271 with CD133 and CD133 with CD34 expressions. The human bone marrow cells (BMCs) and mononucleated cells (MNCs) were detected by flow cytometry with CD45-PerCP, CD271-FITC, CD133-PE and CD34-FITC labelling according to different combinations of design, cells were located and selected repeatedly by FSC, SSC and CD45 after acquirement, then the expressions of CD271, CD133 and CD34 were detected by flow cytometry. The results showed that the expressions of CD271, CD133 and CD34 in BMCs were 0.16%, 0.20% and 0.43% respectively, while their expressions were 0.49%, 0.47% and 1.07% respectively after isolation of MNCs. The co-expressions of CD271(+)CD133(+) before and after isolation of MNCs were (0.02 +/- 0.01)% and (0.03 +/- 0.02)% respectively. The co-expression of CD133(+) and CD34(+) before and after isolation of MNCs were (0.18 +/- 0.11)% and (0.42 +/- 0.23)% respectively (p < 0.01); meanwhile about 90% of cells with CD133(+) expressed CD34 and 40% of cells with CD34(+) expressed CD133. It is concluded that the established method of detection using flow cytometry with three color fluorescence labelling can be used to detect expression of CD271, CD133 and CD34 in BMCs. The cells with CD271 are different from cells with CD133 and CD34, which suggests that the CD271 may be of important role in evaluating and guiding the clinical application of BM MSCs.
AC133 Antigen ; Antigens, CD ; metabolism ; Antigens, CD34 ; metabolism ; Bone Marrow Cells ; cytology ; metabolism ; Cell Line ; Flow Cytometry ; Glycoproteins ; metabolism ; Humans ; Nerve Tissue Proteins ; metabolism ; Peptides ; metabolism ; Receptors, Nerve Growth Factor ; metabolism

This study was aimed to find a better method to isolate and enrich mesenchymal stem cells (MSCs)from bone marrow between CD271 (low affinity nerve growth factor receptor, LNGFR) and CD133 used for immunomagnetic positive selections through comparison of characteristics of MSCs isolated by these two agents. CD271+ and CD133+ cells were isolated from bone marrow and their colony forming unit-fibroblast (CFU-F) efficiency and proliferative capacity were assessed. Cell surface phenotype, adipogenic and osteogenic inductions were also assayed on the cells (after passage 3) isolated by both methods. The results showed that the purities of immunomagnetically selected CD271+ and CD133+ cells were (89.50+/-0.98)% and (88.03+/-3.06)% respectively. The CFU-F median frequency of CD271+ cells was 3 times as high as that of CD133+ cells, no CFU-F was observed in CD271- cells, while a few CFU-F was found in the CD133- cells. Phenotype of cells (after passage 3) isolated by the two methods was same, that is CD34-, CD14-, CD45-, CD90+, CD29+, CD44+, CD105+, CD73+. CD271+ cells possessed faster proliferation and stronger osteogenic and adipogenic differentiation potential than that of CD133+ cells. It is concluded that as compared with CD133 positive selection, CD271 positive selection is a better method for isolating and enriching mesenchymal stem cells from bone marrow.
AC133 Antigen ; Antigens, CD ; immunology ; metabolism ; Bone Marrow Cells ; cytology ; Glycoproteins ; immunology ; metabolism ; Humans ; Immunomagnetic Separation ; methods ; Mesenchymal Stromal Cells ; cytology ; Nerve Tissue Proteins ; immunology ; metabolism ; Peptides ; immunology ; metabolism ; Receptors, Nerve Growth Factor ; immunology ; metabolism ; Stem Cells