OBJECTIVE: To summarize the genetic diagnosis, low-depth copy number variation sequencing (CNV-seq) and prenatal finding in 7 fetuses with 2p16.3 deletions only involving the NRXN1 gene. METHODS: The 7 fetuses have all been found to have loss of heterozygosity at 2p16.3 by CNV-seq, which were verified by quantitative real-time PCR (qPCR). Specific regions of NRXN1 gene deletions were identified, and the CNVs were verified in their parents. Outcome of the pregnancies were followed up. RESULTS: Among 16 502 prenatal samples, 7 fetuses were found to harbor a 120 kb ~ 900 kb microdeletion in the 2p16.3 region, which yielded a prevalence of 0.424‰. The deleted region mainly involved 50 200 000-51 880 000 positions of chromosome 2 and involved only the NRXN1 gene. All of the 7 fetal CNVs were confirmed by qPCR, including 2 cases with heterozygous deletion of exons 1 to 6, 1 with heterozygous deletion of exons 1 to 19, 1 with heterozygous deletion of exons 19 to 22, and 3 with heterozygous deletion of introns 6 to 7 of the NRXN1 gene. Verification in the parents had found that one deletion was inherited from the father, 1 was from the mother, 2 cases were de novo in origin, whilst the remaining 3 had refused parental verification. After genetic counseling, one couple had elected induced abortion, 1 case has not been born yet, whilst the other 5 cases were born healthy. Follow up had identified no mental abnormalities among the children. CONCLUSION Seven fetuses with heterozygous 2p16.3 deletions only involving the NRXN1 gene were detected by CNV-seq. The specific deletion of the NRXN1 gene was verified by qPCR. Prenatal genetic counseling and fertility guidance has been provided to the particular family by combining the results of CNV testing, pedigree analysis and pregnancy outcome.
Female ; Humans ; Pregnancy ; Calcium-Binding Proteins/genetics* ; Cell Adhesion Molecules, Neuronal/genetics* ; DNA Copy Number Variations ; Nerve Tissue Proteins/genetics* ; Neural Cell Adhesion Molecules/genetics* ; Prenatal Diagnosis ; Real-Time Polymerase Chain Reaction ; Infant, Newborn

neural cell adhesion molecule L1-like protein) present in human plasma was investigated. A total of 1,129 blood samples from 575 breast cancer patients, 454 healthy controls, and 100 patients with other malignancies were used to verify and optimize the assay.RESULTS: The diagnostic sensitivity, specificity, and accuracy of the MRM-based proteomic assay were 71.6%, 85.3%, and 77%, respectively; the area under the receiver operating characteristic curve was 0.8323. The proteomic assay did not demonstrate diagnostic accuracy in patients with other types of malignancies including thyroid, pancreatic, lung, and colon cancers. The diagnostic performance of the proteomic assay was not associated with the timing of blood sampling before or after anesthesia.CONCLUSION: The data demonstrated that an MRM-based proteomic assay that measures plasma levels of three specific peptides can be a useful tool for breast cancer screening and its accuracy is cancer-type specific.]]>
Anesthesia ; Biomarkers ; Blood Proteins ; Breast Neoplasms ; Breast ; Carbonic Anhydrases ; Cohort Studies ; Colonic Neoplasms ; Diagnosis ; Humans ; Lung ; Mammography ; Mass Screening ; Mass Spectrometry ; Neural Cell Adhesion Molecules ; Peptides ; Plasma ; Proteomics ; ROC Curve ; Sensitivity and Specificity ; Thyroid Gland

PURPOSE: The significance of neuroendocrine differentiation (NED) in gastric carcinoma (GC) is controversial, leading to ambiguous concepts in traditional classifications. This study aimed to determine the prognostic threshold of meaningful NED in GC and clarify its unclear features in existing classifications. MATERIALS AND METHODS: Immunohistochemical staining for synaptophysin, chromogranin A, and neural cell adhesion molecule was performed for 945 GC specimens. Survival analysis was performed using the log-rank test and univariate/multivariate models with percentages of NED (PNED) and demographic and clinicopathological parameters. RESULTS: In total, 275 (29.1%) cases were immunoreactive to at least 1 neuroendocrine (NE) marker. GC-NED was more common in the upper third of the stomach. PNED, and Borrmann's classification and tumor, lymph node, metastasis stages were independent prognostic factors. The cutoff PNED was 10%, beyond which patients had significantly worse outcomes, although the risk did not increase with higher PNED. Tumors with ≥10% NED tended to manifest as Borrmann type III lesion with mixed/diffuse morphology and poorer histological differentiation; the NE components in this population mainly grew in insulae/nests, which differed from the predominant growth pattern (glandular/acinar) in GC with <10% NED. CONCLUSIONS: GC with ≥10% NED should be classified as a distinct subtype because of its worse prognosis, and more attention should be paid to the necessity of additional therapeutics for NE components.
Adenocarcinoma ; Chromogranin A ; Classification ; Humans ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis ; Neural Cell Adhesion Molecules ; Prognosis ; Stomach ; Stomach Neoplasms ; Synaptophysin

OBJECTIVE: Schizophrenia (SZ) has been associated with the inflammatory-related and immunological pathogenesis. This study investigates the aberration of cytokines in patients with SZ. METHODS: Thirty patients with SZ without antipsychotic treatment for at least two weeks participated. We measured the serum levels of fourteen cytokines at hospital admission and after 8-week antipsychotic treatment. Severity was measured by expanded version of 24-items brief psychiatric rating scale (BPRS-E). Repeated measure analyses of variance were conducted. RESULTS: The interleukin-1 receptor antagonist (IL-1ra) was significantly decreased after 8-week antipsychotic treatment than those of before antipsychotic treatment (F=12.15, df=1/30, p=0.002). Neural cell adhesion molecule 1/CD56 (NCAM-1/CD56) was significantly decreased (F=6.61, df=1/30, p=0.016) among those with second-generation antipsychotics but not first-generation antipsychotics treatment. The changes of BPRS-E-manic and BPRS-E-anxiety scores correlated with the baseline IL-1ra (r=-0.393), IL-6 (r=-0.407), and insulin like growth factor binding protein 3 (r=-0.446). Additionally, the changes of BPRS-E and BPRS-E-negative scores correlated with the changes of brain-derived neurotrophic factor (r=0.372) and interferon-gamma (r=0.375). CONCLUSION: Our study supports that IL-1ra and NCAM-1/CD56 may be considered as markers of developing SZ.
Antipsychotic Agents ; Brain-Derived Neurotrophic Factor ; Brief Psychiatric Rating Scale ; Carrier Proteins ; Cytokines ; Humans ; Insulin ; Interferon-gamma ; Interleukin 1 Receptor Antagonist Protein* ; Interleukin-1 ; Interleukin-6 ; Neural Cell Adhesion Molecules ; Schizophrenia*

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.
Animals ; Methods ; Muscles ; Neural Cell Adhesion Molecules ; Peripheral Nerves ; Rats ; Rats, Sprague-Dawley ; Skin ; Sural Nerve* ; Tibial Nerve*

The present study was aimed to investigate how the induced pluripotent stem cells (iPSCs) and bone marrow mesenchymal stem cells (BMSCs) differentiate into neuron-like cells under the induction of hippocampal microenvironments and Reelin's regulation. iPSCs or BMSCs were co-cultured with WT (wild type) or genotypic hippocampal slice and cerebral homogenate supernatant, then the stem cells' differentiation under the induction of hippocampal environment was observed by using immunofluorescence technique. In the meantime, stem cells were co-cultured with hippocampal slice and cerebral conditioned medium of reeler (Reelin deletion) mouse respectively. The results showed that both adhesive iPSCs and BMSCs on WT hippocampal slice exhibited lamination of double "C" shape with high density on granular and pyramidal layers. The stem cells could differentiate into neuron-like cells with obvious polarization on WT hippocampal slice. In pyramidal cell layer, the differentiated neuron-like cells were oriented vertically with similar shapes of pyramidal cell in vivo, and the cells within molecule layer were arranged horizontally. In addition, adhesive iPSCs and BMSCs could differentiate into Nestin positive neural stem cells and NeuN positive neurons, respectively, under WT hippocampal microenvironment. On the other hand, under induction of hippocampal microenvironment of reeler mouse, iPSCs and BMSCs differentiation could also be seen, but their lamination was in disorder, and cell polarization was irregular. Moreover, differentiation and polarization of the iPSCs and BMSCs were delayed. These results suggest both iPSCs and BMSCs can differentiate into neuron-like cells under the induction of hippocampal microenvironments. Reelin is involved in the regulation of neuronal differentiation and cell polarization. Without Reelin, the cellular lamination and polarization appear irregular, and the stem cells' differentiation is delayed.
Animals ; Cell Adhesion Molecules, Neuronal ; metabolism ; Cell Differentiation ; Cells, Cultured ; Coculture Techniques ; Culture Media, Conditioned ; Extracellular Matrix Proteins ; metabolism ; Hematopoietic Stem Cells ; cytology ; Hippocampus ; Induced Pluripotent Stem Cells ; cytology ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins ; metabolism ; Neural Stem Cells ; cytology ; Neurons ; cytology ; Serine Endopeptidases ; metabolism

Neural cell adhesion molecule (NCAM) is a glycoprotein expressing on the surface of neurons, glial cells, bone cells and natural killer cells. NCAM plays an important role in the process of cell - cell adhesion and cell migration, and is also a model protein to study polysialic acid. In this paper, NCAM gene from mouse mammary gland cells (NMuMG) was cloned into eukaryotic expression vectors pcDNA3.1(+) and transfected into mutant Chinese hamster ovary cells ldlD-14. The stable transfection over-expressing NCAM was obtained through the G418 selection and confirmed by Western blotting. Due to unique characters of ldlD-14 cells, carbohydrate chain of NCAM molecule can be easily manipulated with or without adding galactose in the serum free medium, and this modification can provide the basis for further studies on the effect of glycosylation on NCAM molecular function.
Animals ; CHO Cells ; Cloning, Molecular ; Cricetinae ; Cricetulus ; Female ; Galactose ; Glycosylation ; Mammary Glands, Animal ; cytology ; Mice ; Neural Cell Adhesion Molecules ; biosynthesis ; Polysaccharides ; chemistry ; Sialic Acids ; chemistry ; Transfection

OBJECTIVE: Antidepressants Modulate Neuronal Plasticity. Tianeptine, An Atypical Antidepressant, Might Be Involved In The Restoration Of Neuronal Plasticity; It Primarily Enhances The Synaptic Reuptake Of Serotonin. Ncam140 Is Involved In Neuronal Development Processes, Synaptogenesis And Synaptic Plasticity. We Investigated The Effect Of Tianeptine On The Expression Of Ncam140 And Its Downstream Signaling Molecule In The Human Neuroblastoma Cell Line Sh-sy5y. METHODS: NCAM protein expression was measured in human neuroblastoma SH-SY5Y cells that were cultivated in serum-free media and treated with 0, 10, or 20 microM tianeptine for 6, 24, or 72 hours. NCAM140 expression in the tianeptine treatment group was confirmed by Western blot, and quantified through measurement of band intensity by absorbance. CREB and pCREB expression was identified after treatment with 20 microM tianeptine for 6, 24, and 72 hours by Western blot. RESULTS: Compared to cells treated for 6 hours, cells treated with 0 or 10 microM tianeptine for 72 hours showed a significant increase in NCAM140 expression and cells treated with 20 microM tianeptine showed a significant increase after 24 and 72 hours. The pCREB level in cells treated with 20 microM tianeptine increased in time-dependent manner. CONCLUSION: Our findings indicated that the tianeptine antidepressant effect may occur by induction of NCAM140 expression and CREB phosphorylation.
Antidepressive Agents ; Blotting, Western ; Cell Line ; Culture Media, Serum-Free ; Humans ; Neural Cell Adhesion Molecules ; Neuroblastoma ; Neuronal Plasticity ; Neurons ; Phosphorylation ; Plastics ; Serotonin

Dehydroevodiamine.HCl (DHED) has been reported to prevent memory impairment and neuronal cell loss in a rat model with cognitive disturbance. We investigated the effect of DHED on memory impairment and behavioral abnormality caused by stress. We demonstrated that DHED can improve stress-induced memory impairments and depression-like behaviors by using open-field test, Y-maze test and forced swimming test. DHED treatment significantly recovered the decreases in the levels of neural cell adhesion molecule (NCAM) proteins caused by stress and the decreases in cell viability. Our results suggested that DHED is a potential drug candidate for neuronal death, memory impairment and depression induced by stress.
Animals ; Cell Survival ; Depression* ; Fluoxetine ; Memory* ; Models, Animal ; Neural Cell Adhesion Molecules ; Neurons ; Physical Exertion ; Rats*

PURPOSE: Cell transplantation of myelin-producing exogenous cells is being extensively explored as a means of remyelinating axons in X-linked adrenoleukodystrophy. We determined whether 3,3',5-Triiodo-L-thyronine (T3) overexpresses the ABCD2 gene in the polysialylated (PSA) form of neural cell adhesion molecule (NCAM)-positive cells and promotes cell proliferation and favors oligodendrocyte lineage differentiation. MATERIALS AND METHODS: PSA-NCAM+ cells from newborn Sprague-Dawley rats were grown for five days on uncoated dishes in defined medium with or without supplementation of basic fibroblast growth factor (bFGF) and/or T3. Then, PSA-NCAM+ spheres were prepared in single cells and transferred to polyornithine/fibronectin-coated glass coverslips for five days to determine the fate of the cells according to the supplementation of these molecules. T3 responsiveness of ABCD2 was analyzed using real-time quantitative polymerase chain reaction, the growth and fate of cells were determined using 5-bromo-2-deoxyuridine incorporation and immunocytochemistry, respectively. RESULTS: Results demonstrated that T3 induces overexpression of the ABCD2 gene in PSA-NCAM+ cells, and can enhance PSA-NCAM+ cell growth in the presence of bFGF, favoring an oligodendrocyte fate. CONCLUSION: These results may provide new insights into investigation of PSA-NCAM+ cells for therapeutic application to X-linked adrenoleukodystrophy.
ATP-Binding Cassette Transporters/*metabolism ; Adrenoleukodystrophy/genetics/*therapy ; Animals ; Animals, Newborn ; Bromodeoxyuridine ; Cell Differentiation ; Fibroblast Growth Factor 2/pharmacology ; Fibronectins/metabolism ; Immunohistochemistry ; Neural Cell Adhesion Molecules/*genetics ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Sialic Acids/metabolism ; Stem Cells ; Thyroid Hormones/*metabolism ; Triiodothyronine/pharmacology