Double heterozygous pathogenic mutations in KIF3C and ZNF513 cause hereditary gingival fibromatosis / 国际口腔科学杂志·英文版

Hereditary gingival fibromatosis (HGF) is a rare inherited condition with fibromatoid hyperplasia of the gingival tissue that exhibits great genetic heterogeneity. Five distinct loci related to non-syndromic HGF have been identified; however, only two disease-causing genes, SOS1 and REST, inducing HGF have been identified at two loci, GINGF1 and GINGF5, respectively. Here, based on a family pedigree with 26 members, including nine patients with HGF, we identified double heterozygous pathogenic mutations in the ZNF513 (c.C748T, p.R250W) and KIF3C (c.G1229A, p.R410H) genes within the GINGF3 locus related to HGF. Functional studies demonstrated that the ZNF513 p.R250W and KIF3C p.R410H variants significantly increased the expression of ZNF513 and KIF3C in vitro and in vivo. ZNF513, a transcription factor, binds to KIF3C exon 1 and participates in the positive regulation of KIF3C expression in gingival fibroblasts. Furthermore, a knock-in mouse model confirmed that heterozygous or homozygous mutations within Zfp513 (p.R250W) or Kif3c (p.R412H) alone do not led to clear phenotypes with gingival fibromatosis, whereas the double mutations led to gingival hyperplasia phenotypes. In addition, we found that ZNF513 binds to the SOS1 promoter and plays an important positive role in regulating the expression of SOS1. Moreover, the KIF3C p.R410H mutation could activate the PI3K and KCNQ1 potassium channels. ZNF513 combined with KIF3C regulates gingival fibroblast proliferation, migration, and fibrosis response via the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways. In summary, these results demonstrate ZNF513 + KIF3C as an important genetic combination in HGF manifestation and suggest that ZNF513 mutation may be a major risk factor for HGF.

Rhizomelic chondrodysplasia punctata type Ⅰ in a fetus due to novel pathogenic mutation in PEX7 gene / 中华围产医学杂志

We report a case of a fetus with rhizomelic chondrodysplasia punctata type Ⅰ. Ultrasound examination of the pregnant women at 23 weeks of gestation showed multiple fractures in bilateral femurs, thick metaphysis, severely short, thickened and curved bilateral humerus with multiple fracture images, some of which were callu formation after fracture. The pregnancy was terminated at 23 +2 gestational weeks, samples of fetal skin tissue were taken after birth, and parental peripheral blood was collected for whole exome sequencing, which revealed a frameshift mutation c.179delT (p.F61Lfs*13) in the PEX7 gene of chromosome 6, and the heterozygous deletion (141 kb) occurred in the region of chromosome 6 137105182-137245871, covering the pathogenic gene PEX7. The analysis of parental samples suggested that the mutations were compound heterozygous mutations, none of which had been previously reported and were determined to be pathogenic mutations. The severe clinical phenotype of this case may be caused by severe damage of PEX7 gene contributed by the frameshift mutation and large fragment deletion mutations.

Gene cloning and bioactive analysis of thymosin-β4 from skin of Nanorana yunnanensis / 中国药理学通报

Aim To investigate the gene sequences and pro-angiogenic activities of thymosin-β4 from skin of Nanorana yunnanensis. Methods Two cDNA se-quences of thymosin-β4 from Nanorana yunnanensis designated as pTβ4-1 and pTβ4-2 were obtained by PCR. The tube formation and proliferation of human umbilical vein endothelial cells ( HUVEC ) and chick-en chorioallantoic membrane ( CAM) model were used to observe the pro-angiogenic effects of synthetic pep-tides according to the reduced amino acid sequences of pTβ4-1 and pTβ4-2 in vitro and in vivo, respectively. Results The cDNA sequences of Tβ4-1 and pTβ4-2 were composed of 662 bp and 673 bp, respectively, and their deduced amino acid sequences contained 44 residues which shared highly similarity with those from human , mouse , chicken , claw frog , zebra fish , turbot and Amolops loloensis. Furthermore, the mature amino acid sequences of pTβ4-1 and pTβ4-2 had highly con-served structural regions when compared with other thy-mosin-β4 previously reported. Synthetic peptides could significantly promote proliferation and tube formation of HUVEC and angiogenesis of CAM. Conclusion There are two thymosin-β4 peptides in skins of Nanorana yunnanensis which have pro-angiogenic ac-tivities.

Comparative proteome research of epithelial cells and stroma from invasive ductal carcionma patients / 中国药理学通报

Aim To study the difference of proteins expression of epithelial cells and stroma of breast canc-er patients.Methods Formalin-fixed paraffin-embed-ded tissue samples from invasive ductal carcionma pa-tients were stained by improved HE staining methods. And the neoplastic epithelium and stroma were micro-dissected using laser capture microdissection and ana-lysed by mass spectrometry.Results Total 43 1 differ-ent proteins were detected by mass spectrometry and there were respectively 384 and 298 different kinds of proteins identified in epithelial cells and stroma.A-mong them,25 1 proteins were commonly expressed in two samples,while the contents of 69 and 60 proteins in stroma were respectively higher or lower than the ones in epithelial cells.The expression level and local-ization of proteins identified in epithelial cells and stro-ma were associated with their roles in development and progression of tumor cells.Conclusions The differen-tial expression proteins between epithelial cells and stroma of invasive ductal carcionma patients may func-tion as biomarkers for breast cancer screenning,diag-nosis and prognosis.

Inhibitory effect of mastoparan-like peptide from wasp (Vespa magnifica) venom on angiogenesis / 中国药理学通报

Aim To investigate the anti-angiogenic effect of 12a, the mastoparan-like peptide from wasp ( Vespa magnifica ) venom. Methods The tube for-mation and proliferation of human umbilical vein endo-thelial cells ( HUVEC ) and chicken chorioallantoic membrane ( CAM) model were used to observe the an-ti-angiogenic effect of 12a in vitro and in vivo, respec-tively. Results In the CAM model, 0. 1 μg or 1 μg of 12 a could markedly inhibit angiogenesis induced by 0. 2 μg rh-bFGF with heavy loss of color, decreasing density and obscure frame of the vessels. The inhibi-tion rates of angiogenesis were 60 . 2 % for 0 . 1 μg and 90. 3 % for 1 μg, respectively. Accordingly, in HU-VEC culture experiment, the proliferation and angio-genesis of HUVEC treated by 1 mg·L-1 and 10 mg· L-1 of 12 a were decreased by 55. 4 %, 39. 3 % and 51. 6 %, 26. 7 %, respectively. Conclusion 12a has a significant anti-angiogenic effect in a concentra-tion-dependent manner.

ICOS Regulate Survivin Expression and Sustain T Cell Survival / 生物化学与生物物理进展

To study whether the late-acting co-stimulatory molecules ICOS can suppress the apoptosis and sustain the survival and proliferation of T cells through the survivin pathway, ICOS signals deficient T-cells were infected with adenovirus carried survivin gene, other T-cells were given ICOS co-stimulatory signals, then infected with adenovirus carried dominant-negative mutant survivin gene. Apoptosis and proliferation were determined by TUNEL and CCK-8 respectively. The results show that engagement of ICOS signal increased the expression level of survivin significantly. Survivin can sustain co-stimulatory deficient T cells survival and suppress the apoptosis. Mutant survivin inhibits ICOS signal positive T cells survival and increase its apoptosis. Late-acting co-stimulatory molecules ICOS can suppress the apoptosis and sustain the survival of T cells through the survivin pathway.

Antihemostatic Molecules From Saliva of Blood-Feeding Arthropods / 生物化学与生物物理进展

The ability to feed on vertebrate blood has evolved many times in various arthropod clades. Consequently, saliva of blood-feeding arthropods has proven to be a rich source of antihemostatic molecules. A variety of platelet aggregation inhibitors antagonize platelet responses to wound-generated signals, including ADP, thrombin, and collagen. Anticoagulants disrupt elements of both the intrinsic and extrinsic pathways. Vasodilators include nitrophorins (nitric oxide storage and transport heme proteins), a variety of peptides that mimic endogenous vasodilatory neuropeptides, and proteins that catabolize or sequester endogenous vasoconstrictors. Multiple salivary proteins may be directed against each component of hemostasis, resulting in both redundancy and in some cases cooperative interactions between antihemostatic proteins. The complexity and redundancy of saliva ensures an efficient blood meal for the arthropod, but it also provides a diverse array of novel antihemostatic molecules for the pharmacologist.

Piezoelectric Gene Biosensors for Detection of Pseudomonas aeruginosa Using Signal Amplification Method with Cationic Conjugated Polymers / 中华医院感染学杂志

OBJECTIVE To discuss the feasibility of signal amplification method with cationic conjugated polymers(liposome) applied during the detection of Pseudomonas aeruginosa using piezoelectric gene biosensors.(METHODS) Oligonucleotide probe for P.aeruginosa was immobilized on the surface of gene sensor array and(hybridized) by PCR production of P.aeruginosa.After hybridization,liposome was added.The frequency shifts were recorded and compared with those ones of the control groups.RESULTS The frequency shifts were(significantly) increasing when adding liposome and the compatible concentration of liposome was 0.8?g/?l.(CONCLUSIONS) Liposome signal amplification is proved to be an effective method to amplify the piezoelectric(signal).

全喉切除术后的康复护理 / 中国康复理论与实践

@#目的探讨喉癌患者全喉切除术后的康复护理效果。方法对13例行全喉切除术的喉癌患者进行术后语言康复训练、吞咽功能训练、气管造口护理、心理护理。结果患者的语言功能、吞咽功能、心理功能、造口护理能力均有明显改善。结论全喉切除术后的康复护理可明显提高患者的生存质量,值得引起重视。