Apresentação clínica de osteogênese XV em um menino brasileiro de 4 anos / Clinical presentation of osteogenesis imperfecta XV in a four-year-old brazilian boy

Introdução: Osteogênese Imperfeita (OI) é uma doença genética rara com fragilidade óssea. A classificação inclui muitos tipos. Além do risco de recorrência, o manejo pode variar com o tipo de OI. Relato do caso: Apresentamos um paciente do sexo masculino nascido com 39 semanas, de pais não consanguíneos e saudáveis. A hidrocefalia foi diagnosticada no pré-natal. Com 50 dias de vida, detectamos muitas fraturas e calos ósseos. O teste molecular identificou uma deleção em homozigose do éxon 4 do gene WNT1. Considerações finais: Concluímos que o caso apresentado tinha características clínicas de OI XV, e o teste molecular foi fundamental para o diagnóstico preciso e aconselhamento genético.

Introduction: Osteogenesis Imperfecta (OI) is a rare genetic disease with bone fragility. The classification includes many types. In addition, the risk of a recurrence, the management can vary with the kind of OI. Case report: We report a male patient born at 39 weeks from non-consanguineous healthy parents. The patient was diagnosed with Hydrocephalus at prenatal. At 50 days of life, we detected many fractures and bone calluses. The molecular test identified a homozygous deletion of exon 4 of the WNT1 gene. Final considerations: We conclude this case had clinical features of OI XV, and the molecular test was fundamental for the precise diagnosis and the genetic counseling.

Mechanism of Hedysarum Polysaccharide in Diabetic Nephropathy in db/db Mice Based on Wnt/β-catenin Signal Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of Hedysarum polysaccharides （HPS） on the Wnt/β-catenin signal pathway in db/db mice with diabetic nephropathy. MethodFifty db/db mice were randomly divided into model group， irbesartan group， and high， middle， and low-dose HPS experimental groups according to their body mass， with 10 mice in each group， and another 10 C57BL/6 mice were selected as a normal group. The normal group and the model group were given 5 mL·kg-1·d-1 distilled water， the irbesartan group was given 22.75 mg·kg-1·d-1 irbesartan suspension， and the high， middle， and low-dose HPS experimental groups were given 200， 100， and 50 mg·kg-1·d-1 HPS suspensions， respectively. The mice in the 6 groups were given intragastric administration once a day for 12 weeks. The general state， blood glucose （GLU）， 24 h urine protein （UTP）， blood creatinine （SCr）， and urea nitrogen （BUN） of mice in each group were determined. The pathological changes in the kidney tissue were observed by hematoxylin-eosin staining （HE）. The protein and mRNA expression levels of Wnt1， β-catenin， glycogen synthesis kinase-3β （GSK-3β）， and phosphorylated GSK-3β （p-GSK-3β） in the kidney were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultAfter treatment for 12 weeks， as compared with the normal group， the general state of mice in the model group was worse and the pathological ultrastructural lesions of kidney tissues were obvious. The levels of GLU， 24 h UTP， SCr， and BUN in the model group increased （P<0.01）. As compared with the model group， the general state and renal pathological ultrastructure of mice in the high and middle-dose HPS groups were improved to some extent， and the levels of SCr， BUN， and 24 h UTP in the high and middle-dose HPS groups decreased （P<0.05，P<0.01）. As compared with the normal group， the expression levels of Wnt1， β-catenin， GSK-3β， and p-GSK-3β protein and mRNA in the model group were higher （P<0.01）， while the expression levels of Wnt1， β-catenin， GSK-3β， and p-GSK-3β protein and mRNA in the high and middle-dose HPS groups were lower than those in the model group （P<0.05，P<0.01）. ConclusionHPS can alleviate the renal injury of diabetic nephropathy to some extent， and its mechanism may be related to the inhibition of the activation of the Wnt/β-catenin signal pathway.

Effect of electroacupuncture on urodynamics and expression of Wnt-1, β-catenin, and Ngn1 in the spinal cord in rats with bladder detrusor hyperreflexia due to supersacral spinal cord transection / 针刺研究

OBJECTIVE: To investigate the effect of electroacupuncture (EA) at "Dazhui" (GV14) and "Ciliao" (BL32) on rats with bladder detrusor hyperreflexia (DH) after supersacral spinal cord transection, as well as the mechanism of EA in improving the urinary function by regulating the expression of Wnt-1, β-catenin and Neurogenin 1(Ngn1). METHODS: A total of 48 female Sprague-Dawley rats were randomly divided into sham-operation group, model control group, EA group, and EA control group, with 12 rats in each group. T10 spinal cord transection (SCT) was performed by surgery. The Basso, Beattie and Bresnahan (BBB) score was used to evaluate the motor function of SCT rat, and the Crede technique was used to assist urination. After the urine volume became stable, the urodynamic test was used to determine whether a rat model of DH was successfully established. The rats in the EA group were given EA at GV14 and BL32, and those in the EA control group were given EA (10 Hz/50 Hz, 20 min) at the acupuncture points at 1 cm next to GV14 and BL32 at both sides alternatively. EA was performed once a day for one week. Urodynamic parameters were used to evaluate urinary function. Western blot and immunohistochemistry were used to measure the expression of Wnt-1 and β-catenin in the spinal cord, and immunofluorescence assay was used to measure the expression of Ngn1 in the spinal cord. RESULTS: The BBB score of the model control group significantly decreased compared with that of the sham-operation group(P<0.01), and the EA group was significantly higher than the model control group and the EA control group. Compared with the sham-operation group, the model control group had significant increases in bladder base pressure, maximum pressure, and leak point pressure (P<0.01) and significant reductions in maximum bladder capacity and compliance (P<0.01). Compared with the model control group, the EA group had significant reductions in bladder base pressure, maximum pressure, and leak point pressure (P<0.01) and significant increases in maximum bladder capacity and compliance (P<0.01, P<0.05). Compared with the EA group, the EA control group had significant increases in bladder base pressure, maximum pressure, and leak point pressure (P<0.01) and significant reductions in maximum bladder capacity and compliance (P<0.01, P<0.05). Compared with the sham-operation group, the model control group had significant increases in the protein expression of Wnt-1 and β-catenin (P<0.05, P<0.01) and a signi-ficant reduction in the protein expression of Ngn1 in the spinal cord (P<0.01). Compared with the model control group, the EA group had significant increases in the protein expression of Wnt-1, β-catenin and Ngn1 in the spinal cord (P<0.01). Compared with the EA group, the EA control group had significant reductions in the protein expression of Wnt-1, β-catenin, and Ngn1 in the spinal cord (P<0.01). CONCLUSION: EA at GV14 and BL32 can significantly improve urinary function in rats with bladder DH due to SCT, partially by activating the Wnt/β-catenin signaling pathway and promoting the protein expression of Wnt-1, β-catenin and Ngn1.

Estudo da expressão imunohistoquímica de SO2, FGF-10 e WNT-1 em lesões odontogênicas epiteliais benignas / Study of the immunohistochemical expression of SO2, FGF-10 and WNT-1 in benign epithelial odontogenic lesions

Os dentes desenvolvem-se a partir de interações sequenciais entre o epitélio e o mesênquima derivado da crista neural em diferentes estágios de histodiferenciação e morfodiferenciação. Ao final da odontogênese, espera-se que as estruturas que participaram da formação destes tecidos desapareçam ou permaneçam quiescentes. Não é incomum que os remanescentes epiteliais da odontogênese originem lesões, como cistos e tumores odontogênicos. No desenvolvimento dentário precoce, a manutenção das células-tronco é regulada por uma série de fatores de transcrição específicos, que inclui OCT-4, SOX-2, Nanog, Stat-3 e c-Myc e diversos outros genes Homeobox e vias de transcrição (SHH, Wnt/ß-catenina, FGF, BMP) contribuem para o destino e diferenciação celular. No entanto, há a participação destes genes e vias na patogênese de vários tipos de tumores. O objetivo do presente estudo foi avaliar a imunoexpressão de SOX2, FGF-10 e Wnt-1 em uma série de casos de lesões odontogênicas e alguns espécimes de germes dentários. A amostra consistiu de 20 Ceratocistos Odontogênicos (CO), 20 Ameloblastomas sólidos (AM), 20 Tumores odontogênicos adenomatoides (TOA), 10 Tumores odontogênico epitelial calcificante (TOEC) e 05 casos de germes dentários usados comparativamente. A imunoexpressão foi avaliada de acordo com o percentual de células epiteliais imunomarcadas e intensidade de células positivas resultando na pontuação de imunomarcação total (PIT) que variou de 0 a 7. A análise da imunoexpressão da SOX2 revelou positividade na maioria dos casos das lesões estudadas. A pontuação de imunomarcação para SOX2 revelou haver diferença estatisticamente significativa entre os grupos de lesões estudadas, com maior frequência em CO e TOEC (p <0,001). Após o pareamento, observou-se diferença significativa entre AM e CO, AM e TOEC, CO e TOA, CO e TOEC e, TOA e TOEC (p <0,05). A análise da imunoexpressão da FGF-10 e Wnt-1 revelou positividade em todos os casos das lesões estudadas, mas sem diferença estatisticamente significativa entre os grupos de lesões estudadas (p = 0,628). Houve diferença significativa em relação aos escores de positividade para Wnt-1 (p <0,001) com maior frequência em CO e TOA. Após o pareamento, observou-se existir diferença estatisticamente significativa entre AM e CO, AM e TOEC, CO e TOEC e, TOA e TOEC (p <0,05). O padrão de expressão de SOX2, FGF-10 e Wnt-1, em germes dentários e nas lesões odontogênicas aqui avaliadas, confirma a participação destas vias na odontogênese e também no desenvolvimento das lesões odontogênicas (AU).

Dental development occurs from sequential interactions between the epithelium and the mesenchyme derived from the neural crest at different stages of histodifferentiation and morphodifferentiation. At the end of tooth development, the structures that participated in the formation of these tissues are expected to disappear or remain quiescent. It is not uncommon that the epithelial remnants of the tooth development originate lesions such as odontogenic cysts and tumors. In early tooth development, stem cell maintenance is regulated by specific transcription factors, which includes OCT-4, SOX-2, Nanog, Stat-3 and c-Myc and several other Homeobox genes and transcription pathways (SHH, Wnt/ß-catenin, FGF, BMP) contribute to cell fate and differentiation. However, there is involvement of these genes and pathways in the pathogenesis of several types of tumors. The aim of the present study was to evaluate the immunoexpression of SOX2, FGF-10 and Wnt-1 in a case series of odontogenic lesions and some specimens of dental germs. The sample consisted of 20 Odontogenic Keratocysts (OK), 20 solid ameloblastomas (AM), 20 adenomatoid odontogenic tumors (AOT), 10 calcifying epithelial odontogenic tumors (CEOT) and 5 dental gerns for comparison. Immunoexpression was evaluated according to the percentage of immunostained epithelial cells and intensity of the positive cells resulting in total immunostaining score (PIT) ranging from 0 to 7. The analysis of SOX2 immunoexpression revealed positivity in most cases of the lesions studied. The immunostaining score for SOX2 revealed a statistically significant difference between the groups of lesions studied, with a higher frequency in OK and CEOT (p < 0.001). After pairing, we observed a significant difference between AM and OK, AM and CEOT, OK and AOT, OK and CEOT, and AOT and CEOT (p <0.05). Analysis of the FGF-10 and Wnt-1 immunoexpression revealed positivity in all cases of the lesions studied, with no statistically significant difference between the groups of lesions studied (p = 0.628). There was a significant difference in relation to the positivity scores for Wnt-1 (p <0.001) with higher frequency in OK and AOT. After pairing, there was a statistically significant difference between AM and OK, AM and CEOT, OK and CEOT and, AOT and CEOT (p <0.05). The expression pattern of SOX2, FGF-10 and Wnt-1 in dental germs and odontogenic lesions evaluated here confirms the participation of these pathways in the tooth development as well as in the development of odontogenic lesions (AU).

Wnt1/β-catenin signaling up-regulates spinal VGLUT2 expression to maintain neuropathic pain in mice / 中国药理学与毒理学杂志

OBJECTIVE The present study was aimed to investigate the role of Wnt/β-catenin sig-naling in spinal VGLUT2 regulation and neuropathic pain. METHODS To elucidate the association be-tween VGLUT2 and neuropathic pain,we determined the expression and distribution characteristics of VGLUT2 in mice subjected to spared nerve injury(SNI),and then observed the effects of two VGLUT2 targeting shRNAs on mechanical allodynia and glutamate release.The effects of Wnt/β-catenin signal-ing on VGLUT2 expression and pain behavior were investigated by using Wnt agonist,Wnt1,and Wnt/β-catenin pathway inhibitor XAV939 in SNI mice.RESULTS SNI surgery induced significant up-regula-tion of VGLUT2 on postoperative days 7,14,and 21.Double immunofluorescence labeling of VGLUT2 with NeuN,MAP2,Iba-1,or GFAP showed that VGLUT2 was mainly expressed in neurons in the dor-sal horn of the spinal cord after SNI(NeuN,MAP2).Intrathecal administration of VGLUT2 shRNAs be-fore or after SNI surgery significantly decreased mechanical allodynia and glutamate release. Mean-while,Wnt1/β-catenin signaling increased significantly after SNI surgery.Over-expression of β-catenin in PC12 cells increased VGLUT2 protein level,intrathecal administration of Wnt agonist or Wnt1 signifi-cantly increased VGLUT2 protein expression in spinal cord, while Wnt/β-catenin pathway inhibitor XAV939 decreased VGLUT2 expression in PC12 cells and spinal cord.Additionally,intrathecal admin-istration of XAV939 7 days after SNI significantly attenuated mechanical allodynia in mice, which was in accordance with down-regulation of VGLUT2 protein levels.VGLUT2 shRNAs significantly attenuat-ed Wnt agonist or Wnt1 induced mechanical allodynia. CONCLUSION Wnt1/β-catenin signaling path-way up-regu-lates the spinal VGLUT2 expression,and this regulation is involved in neuropathic pain behavior.

miR-34a Inhibitor May Effectively Protect against Sevoflurane-Induced Hippocampal Apoptosis through the Wnt/β-Catenin Pathway by Targeting Wnt1

PURPOSE: Research has shown that sevoflurane-induced toxicity causes neurodegeneration in the developing brain. miR-34a has been found to negatively regulate ketamine-induced hippocampal apoptosis and memory impairment. However, the role of miR-34a in sevoflurane-induced hippocampal neurodegeneration remains largely unclear. MATERIALS AND METHODS: C57/BL6 mice (7-day-old) inhaled 2.3% sevoflurane for 2 h/day over 3 consecutive days. miR-34a expression was reduced through intracerebroventricular injection with miR-34a interference lentivirus vector (LV-anti-miR-34a) into mouse hippocampus after anesthesia on the first day of exposure. Hippocampal apoptosis was detected by TUNEL assay and flow cytometry analysis. Spatial memory ability was evaluated by the Morris water maze test. The interaction between miR-34a and Wnt1 was confirmed by luciferase reporter assay, RNA immunoprecipitation, Western blot, and immunofluorescence staining. The effects of miR-34a on protein levels of B-cell lymphoma 2 (Bcl-2), bcl-2-like protein 4 (Bax), and Wnt/β-catenin pathway-related proteins were evaluated using Western blot analysis. RESULTS: Sevoflurane upregulated hippocampal miR-34a, and miR-34a inhibitor attenuated sevoflurane-induced hippocampal apoptosis and memory impairment. miR-34a negatively regulated Wnt1 expression by targeting miR-34a in hippocampal neurons. Moreover, forced expression of Wnt1 markedly undermined miR-34a-mediated enhancement of sevoflurane-induced apoptosis of hippocampal neurons, while Wnt1 silencing greatly restored anti-miR-34a-mediated repression of sevoflurane-induced apoptosis of hippocampal neurons. Increased expression of miR-34a inhibited the Wnt/β-catenin pathway in hippocampal neurons exposed to sevoflurane, while anti-miR-34a exerted the opposite effects. CONCLUSION: miR-34a inhibitor may effectively protect against sevoflurane-induced hippocampal apoptosis via activation of the Wnt/β-catenin pathway by targeting Wnt1.

The expression of wnt1 in oral submucous fibrosis / 实用口腔医学杂志

Objective:To observe the expression of wnt1 in patients with oral submucous fibrosis(OSF) before and after treatment.Methods:40 patients with OSF were treated with triamcinolone acetonide combined with salvia miltiorrhiza,Before and after 4 weeks treatment,pain score of VAS and mouth opening(MO) were examined.wnt1 protein in saliva and gingival crevicular fluid(GCF) was examined by ELISA,wnt1 mRNA expression in buccal mucosa tissue was examined by real-time fluorescent quantitative PCR.20 healthy subjects were served as the controls.Results:The expression of wnt1 in OSF group[buccal tissue RT-PCR (36.89 ± 10.40) × 10-5,saliva ELISA (61.61 ± 4.45) ng/L,GCF ELISA (56.20 ± 3.65) ng/L] were significantly higher than that of control group [buccal tissue RT-PCR (4.63 ± 1.53) × 10-5,saliva ELISA (40.26 ± 3.00) ng/L,GCF ELISA (53.45 ± 1.74) ng/L)] (P ＜ 0.01).In OSF group,after treatment VAS was decreased(P ＜0.01),MO increased(P ＜0.01)),Buccal mucosa wnt1 mRNA level was positively correlated with wnt1 protein in saliva and GCF,negativity with MO (P ＜ 0.05),saliva wnt1 was positively correlated with VAS and GCF wnt1,negitively with MO(P ＜ 0.05).Conclusion:Wnt1 might take part in the occurrence and development of OSF.The detection of wnt1 in saliva and GCF might be a noninvasive method for the evaluation of OSF treatment.

Expression of Wnt1 and β-catenin in the gingival tissure with gingival overgrowth induced by nifedipine / 实用口腔医学杂志

Objective:To study the expression of Wnt/β-catenin signaling pathway related proteins Wnt1 and β-catenin protein in gingival tissues of the patients with drug-induced gingival overgrowth(DGO) caused by nifedipine.Methods:Wnt1 and β-catenin expression were tested with Western Blot and RT-PCR in gingival tissues of 10 cases of DGO induced by nifedipine,10 cases of high blood pressure with gingival hyperplasia(without use of any medicine) and 10 cases of healthy control.Results:In the gingival tissues of DGO group the levels of Wnt1 and β-catenin protein and mRNA were significantly higher than those of the healthy control group(P ＜ 0.05) and the high blood pressure group (P ＜ 0.05).Conclusion:The levels of Wnt1 and β-catenin are increased in nifedipine induced gingival hyperplasia.The gingival hyperplasia may be caused by the promotion of gingival fibroblast proliferation through Wnt/β-catenin signaling pathway.

Expression and clinical implications of Wnt-1 and FZD-1 in small cell lung cancer patients / 实用医学杂志

Objective To investigate the expressions of Wnt-1 and FZD-1 in small cell lung cancer(SCLC) patients and their relations with chemotherapy resistance,clinical feature and prognosis.Methods Peripheral blood specimens were collected from 41 SCLC patients.The expression of Wnt-1 and FZD-1 in peripheral blood monouclear cells (PBMC) were detected.The relationship among the expression of Wnt-1 and FZD-1,clinicopathologic feature and prognosis was analyzed.Results The relative expression of Wnt-1 and FZD-1 in chemotherapy resistant group was significantly higher than that in chemotherapy sensitive group (all P ＜ 0.05).The expression of Wnt-1was positively correlated with that of FZD-1 (r =0.186,P ＜ 0.05).The FZD-1expression level was not correlated with patients' age,sex and smoking history (all P ＞ 0.05),but closely with clinic-staging (P =0.008).The Wnt-1 expression level was not correlated with patients' clinical features (all P ＞ 0.05).There was statistical difference in median survival time between Wnt-1 and FZD-1 high-expression group and low-expression group.Conclusions Wnt-1 and FZD-1relationships with chemotherapy resistance and prognosis.Wnt-1 and FZD-1 may act as an important role in chemotherapy resistance of SCLC and could be served as indicators for the chemotherapy resistance and outcome assessment of SCLC.

Effect of Wnt1 on the expression of Cyclin D1 protein in human corneal epithelial cells / 实用医学杂志

Objective To investigate the effect of Wnt1 on the expression of Cyclin D1 in human corneal epithelial cells and its related molecular mechanisms. Methods 12 T25 cell culture flasks were cultured after hu-man corneal epithelial cells anabiosis ,culture and continuous passage for 2 times. Culture flasks were divided into 3 groups with 4 culture flasks in each group. Twenty-five ng/mL and 50 ng/mL recombinant human Wnt1 protein were added in two of the groups,and one group without T-cell culture medium(Wnt1)was used as control. Cells cultured in T25 flask were taken from three groups at different time(6 h,24 h,48 h and 72 h). The total number of corneal epithelial cells in each group was calculated. Expression of Cyclin D1 in corneal epithelial cells was de-tected by Western blot. Results The expression of Cyclin D1 protein in the control group decreased gradually from 0 h to 48 h,and reached the lowest level at 48 h and increased at 72 h. Cyclin D1 protein expression in 25 ng/mL group at 6 h after Wnt1 was added was not detected,and Cyclin D1 protein expression in 50 ng/mL group in-creased. The expression of Cyclin D1 protein in 25 ng/mL group and 50 ng/mL group was significantly higher than that in control group at 24 h,48 h and 72 h,reaching the peak at 48 h and decreased at 72 h. Compared with the control group,the growth rate of corneal epithelial cells in 25ng/ml group and 50ng/ml group increased after Wnt1 was added. There was significant difference in 72 h,but no significant difference in 6h,24h and 48h. Conclu-sions The stimulation of Wnt1 protein can enhance the expression of Cyclin D1 in a certain time range,and has a positive correlation with Wnt1 protein. As one of the target genes of Wnt1 signaling pathway,Cyclin D1 may play an important role in the repair of corneal epithelial injury and its cell proliferation and differentiation.

Mechanism of Wnt/β-catenin signaling pathway in enhanced malignant phenotype of non-small cell lung cancer induced by anti-angiogenesis therapy

Objective: To study the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of A549 cells of human non-small cell lung cancer induced by the anti-angiogenesis therapy. Methods: The siRNA technique was employed to inhibit the expression of vascular endothelial growth factor (VEGF) in A549 cells and simulate the clinical course of anti-angiogenesis therapy. Real-time PCR and western blot were used to study the change in the expression of Wnt/β-catenin signaling molecules at the mRNA and protein level respectively, as well as the effect on the epithelial mesenchymal transition in A549 cells. The proliferation and invasion abilities of tumor cells were detected to discuss the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of non-small cell lung cancer induced by the anti-angiogenesis therapy. Results: The specific siRNA could significantly inhibit the expression of VEGF in cells to simulate the anti-angiogenesis therapy. Under the action of 50 nM VEGF siRNA, the proliferation ability of A549 significantly increased (P < 0.05). After being treated with VEGF siRNA, the invasion ability of cells increased. Twenty-four hours after the transcription of 50 nM siRNA into cells, the number of cells that come through the membrane was 278.3 ± 12.9. Compared with the Ctrl siRNA group, when VEGF was inhibited, the expression of β-catenin and Cyclin D1 increased by 86% and 55% respectively. Meanwhile, the expression of E-cadherin decreased, while the one of vimentin increased. Conclusions: siRNA can significantly inhibit the expression of VEGF. For the anti-angiogenesis therapy, the inhibited expression of VEGF can activate the Wnt/β-catenin signaling pathway to cause the epithelial mesenchymal transition and then the enhanced malignant phenotype of non-small cell lung cancer.

Effect of Qinghua Gushen Paidu Granule on expression of Wnt1 and β-catenin in Wnt signaling pathway in renal fibrosis rats / 中草药

Objective: To investigate the influence and mechaninsm of renal interstitial fibrosis of Qinghua Gushen Paidu Granule (QGPG) on renal tubular epithelial mesenchymal transition in unilateral ureteral obstruction rats. Methods: The male Sprague-Dawley (SD) rats (108 cases) were randomly divided into Sham-operated group, model group, high-, mid-, low-dose QGPG groups (HQ, MQ, and LQ groups), and Lotensin treated group, 18 in each group. The rats in HQ, MQ, LQ, and Lotensin treated groups were respectively ig administered with QGPG (3, 1.5, and 0.75 g/kg) and Lotensin (1.6 mg/kg, dissolved in nomal saline). At the same time, nomal saline was ig administered in Sham-opration and model groups, once daily. At days 7, 14, and 21, six rats in each group were randomly sacrificed. Serum blood urea nitrogen (BUN) and serum creatitine (SCr) were tested. Also their left surgery renal tissues were collected for pathological examination. The pathological changes of the obstruction renal tissue were examined by HE and Masson staining. The protein expression of Wnt1 and β-catenin was detected by immunohistochemical staining. Results: Compared with the Sham-operation group, serum levels of BUN and SCr of rats in other groups were increased (P<0.05), protein expression level of β-catenin increased in the renal tissue (P<0.05). The renal interstitial fibrosis degree was gradually aggratated along with the ureteral obstruction time. Compared with the model group, after the treatment, serum levels of BUN and SCr in rats decreased significantly (P<0.05), protein expression of β-catenin decreased in the renal tissue (P<0.05). Compared with the Sham-operation group, the protein expression of Wnt1 in other group increased (P<0.05). The protein expression of Wnt1 was the highest in day 7 after ureteral obstruction (P<0.05), then decreased. Compared with the model group, after the treatment by drugs, the protein expression of Wnt1 decreased in the renal tissue (P<0.05). Conclusion: QGPG may ameliorate renal interstitial fibrosis by down-regulating the expression of Wnt1 and β-catenin.

Effects of Weipixiao (胃痞消) on Wnt pathway-associated proteins in gastric mucosal epithelial cells from rats with gastric precancerous lesions / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the effects of Weipixiao (胃痞消, WPX) on Wnt pathway-associated proteins in gastric mucosal epithelial cells from rats with gastric precancerous lesions (GPL).</p><p><b>METHODS</b>Sprague Dawley rats were randomly divided into control, model, vitacoenzyme (0.2 g·kg(-1)·day(-1)), WPX high-dose (H-WPX, 15 g·kg(-1)·day(-1)), WPX medium-dose (M-WPX, 7.5 g·kg(-1)·day(-1)) and WPX low-dose (L-WPX, 3.75 g·kg(-1)·day(-1)) groups. After successfully establishing the GPL model, the rats were consecutively administered WPX or vitacoenzyme by gastrogavage for 10 weeks. Differential expression of Leucine-rich repeat-containing G-proteincoupled receptor 5 (Lgr5), matrix metalloproteinase-7 (MMP-7), Wnt1, Wnt3a, and β-catenin in gastric mucosal epithelial cells in all groups were immunohistochemically detected, and the images were taken and analyzed semiquantitatively by image pro plus 6.0 software.</p><p><b>RESULTS</b>Gastric epithelium in the model group showed significantly higher expression levels of Lgr5, MMP-7, Wnt1, Wnt3a and β-catenin than those of the control group(P<0.01). Interestingly, we also observed Lgr5+ cells, which generally located at the base of the gastric glandular unit, migrated to the luminal side of gastric epithelium with GPL. The expression levels of Lgr5, MMP-7, Wnt1, and β-catenin were all down-regulated in the L-WPX group as compared with those of both model and vitacoenzyme groups (P<0.05). A similar, but nonsignificant down-regulation in expression level of Wnt3a was noted in all WPX groups (P>0.05).</p><p><b>CONCLUSION</b>Our findings suggested that the therapeutic mechanisms of WPX in treating GPL might be related with its inhibitory effects on the expressions of Lgr5, MMP-7, Wnt1, β-catenin and the aberrant activation of Wnt/β-catenin pathway.</p>

Mechanism of Wnt/β-catenin signaling pathway in enhanced malignant phenotype of non-small cell lung cancer induced by anti-angiogenesis therapy

OBJECTIVE@#To study the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of A549 cells of human non-small cell lung cancer induced by the anti-angiogenesis therapy.@*METHODS@#The siRNA technique was employed to inhibit the expression of vascular endothelial growth factor (VEGF) in A549 cells and simulate the clinical course of anti-angiogenesis therapy. Real-time PCR and western blot were used to study the change in the expression of Wnt/β-catenin signaling molecules at the mRNA and protein level respectively, as well as the effect on the epithelial mesenchymal transition in A549 cells. The proliferation and invasion abilities of tumor cells were detected to discuss the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of non-small cell lung cancer induced by the anti-angiogenesis therapy.@*RESULTS@#The specific siRNA could significantly inhibit the expression of VEGF in cells to simulate the anti-angiogenesis therapy. Under the action of 50 nM VEGF siRNA, the proliferation ability of A549 significantly increased (P < 0.05). After being treated with VEGF siRNA, the invasion ability of cells increased. Twenty-four hours after the transcription of 50 nM siRNA into cells, the number of cells that come through the membrane was 278.3 ± 12.9. Compared with the Ctrl siRNA group, when VEGF was inhibited, the expression of β-catenin and Cyclin D1 increased by 86% and 55% respectively. Meanwhile, the expression of E-cadherin decreased, while the one of vimentin increased.@*CONCLUSIONS@#siRNA can significantly inhibit the expression of VEGF. For the anti-angiogenesis therapy, the inhibited expression of VEGF can activate the Wnt/β-catenin signaling pathway to cause the epithelial mesenchymal transition and then the enhanced malignant phenotype of non-small cell lung cancer.

Effect of irinotecan hydrochloride injection on serum GPX3 and WISP2, FGFBP1 in tumor tissue fluid of patients with advanced rectal cancer / 中国生化药物杂志

Objective To analyse the effect of irinotecan hydrochloride injection on serum glutathione peroxidase 3 (GPX3), and WNT1 induced signaling pathway protein 2 (WISP2) and fibroblast growth factor binding protein 1 (FGFBP1) in tumor tissue fluid of patients with advanced rectal cancer.Methods 90 patients who were diagnosed with advanced rectal cancer in the hospital were collected.All patients were randomly divided into experimental group and control group,control group were treated with oxaliplatin +calcium folinate +fluorouracil chemotherapy, and experimental group were treated with oxaliplatin +calcium folinate +irinotecan hydrochloride injection chemotherapy.The treatment were repeated every four weeks, a total of six times.The serum GPX3 content, and WISP2, FGFBP1 levels in tumor tissue fluid were detected in two groups pre-and post treatment.The clinical efficacy was evaluated.ResuIts Compared with control group, the serum level of GPX3 in experimental group increased significantly (P<0.05);WISP2 level in tumor tissue fluid of experimental group increased significantly (P<0.05);FGFBP1 level in tumor tissue fluid of experimental group decreased significantly ( P<0.05 ) .The total efficiency of experimental group was higher than that of control group ( 64.44%vs.42.22%;χ2 =4.46,P<0.05), and the clinical benefit rate of experimental group was significantly higher than that of control group(93.33%vs.75.56%;χ2 =5.41,P<0.05).ConcIusion The irinotecan hydrochloride injection could increased levels of serum GPX3 and WISP2 in tumor tissue fluid, reduce FGFBP1 level in tumor tissue fluid, which has good clinical curative effect.

MicroRNA-27 Promotes Odontoblast Differentiation via Wnt1 Signaling

MicroRNA (miRNA, miR) is essential in regulating cell differentiation either by inhibiting mRNA translation or by inducing its degradation. However, the role of miRNA in odontoblastic cell differentiation is still unclear. In this study, we examined the molecular mechanism of miR-27-mediated regulation of odontoblast differentiation in MDPC-23 mouse odontoblastic cells derived from mouse dental papilla cells. The results of the present study demonstrated that the miR-27 expression increases significantly during MDPC-23 odontoblastic cell differentiation. Furthermore, miR-27 up-regulation promotes the differentiation of MDPC-23 cells and accelerates mineralization without cell proliferation. The over-expression of miR-27 significantly increased the expression levels of Wnt1 mRNA and protein. In addition, the results of target gene prediction revealed that Wnt1 mRNA has an miR-27 binding site in its 3'UTR, and is increased by miR-27. These results suggested that miR-27 promotes MDPC-23 odontoblastic cell differentiation by targeting Wnt1 signaling. Therefore, miR-27 is a critical odontoblastic differentiation molecular target for the development of miRNA based therapeutic agents in dental medicine.

Expression of Wnt-1 and β-catenin in cervical squamous cell carcinomas and relationship with metastasis / 临床与实验病理学杂志

Purpose To investigate the expression of Wnt-1 and β-catenin protein in cervical squamous cell carcinomas ( CSCC) and their relationship with invasion and lymph node metastasis. Methods Expression of Wnt-1 and β-catenin protein were examined on immunohistochemistry containing 78 specimens of CSCC and 30 specimens of normal cervical tissues. Results The positive rates of Wnt-1 and β-catenin protein in normal cervical tissues were 20.0% and 10.0% respectively. The positive rates of Wnt-1 andβ-cate-nin protein in CSCC were 56.4%, and 74.4% respectively. There was a significant difference between the two groups (P0.05). Spearman analysis showed that the expression of Wnt-1 protein was positive related to the expression ofβ-cate-nin protein (rs =0.490, P<0.001). Conclusion The abnormal expression of Wnt-1 and β-catenin may be involved in initiation, development, invasion, and metastasis of CSCC, and it is suggested that Wnt-1 and β-catenin be considered as potential markers for invasion, metastasis, and prognosis.

The role of Wnt signal pathway related proteins in the development of spontaneous breast cancer in TA2 mice / 安徽医科大学学报

Objective To investigate the role of Wnt signal pathway related proteins in the tumorigenesis of sponta-neous breast cancer in TA2 mice. Methods Mammary glands were collected from tissues of normal 5 cases of TA2 mice. Spontaneous breast cancers and relevant mammary glands precancerous lesions were harvested from 5 cases of TA2 mice. Mammary tissue samples from normal TA2 mice, precancerous lesions and cancer tissues of spontaneous breast cancer-bearing TA2 mice were subsequently used to detect the expression of Wnt1,Wnt5a andβ-catenin via immunohistochemical staining. Results ① Results of immunohistochemical staining showed that the positive ex-pression of Wnt1 and Wnt5 a located in cytoplasm in spontaneous breast cancers and mammary gland precancerous lesions from TA2 mice. The normal mammary glands were negative for Wnt1 and Wnt5a staining. The cytoplasm of precancerous lesions showed higher expression for Wnt1 and Wnt5a than them in the breast cancer. β-catenin in breast cancer and precancerous lesions were abnormal cytoplasmic expression. The expression level in breast cancer was higher than in the precancerous lesions. In normal mammary gland, the positive expression ofβ-catenin mainly located in the cytomembrane. ② The positive expression rates of Wnt1, Wnt5a and β-catenin in normal breast group,precancerous group and breast cancer group were ( 4. 46 ± 3. 57 )%, ( 96. 50 ± 6. 30 )%, ( 90. 00 ± 1. 17 )%, ( 2. 27 ± 4. 55 )%, ( 96. 24 ± 6. 00 )%, ( 95. 90 ± 4. 32 )%, ( 4. 78 ± 3. 57 )%, ( 60. 59 ± 5. 63 )%, (84. 87 ± 2. 56)%,respectively. The positive expression rates of the three in precancerous group and breast cancer group were significantly higher than those in normal breast group(P0. 05). Compared with breast cancer group,the precancerous group had lower positive expression rate of β-catenin and the differences also had statistical significance ( P <0. 05 ) . Conclusion Wnt1 , Wnt5 a and β-catenin promote the progression of spontaneous breast cancer in TA2 mice.

Expression and significance of Wnt1 and β-catenin proteins in breast invasive ductal carcinoma / 中国医师杂志

Objective To investigate the expressions of Wnt1 and β-catenin proteins in mammary cancer and its relationship with clinical pathological characteristics,and explore its role in the pathogenesis of breast cancer.Methods Immunoshistochemisty (SP method) was used to detect the expressions of Wnt1 and β-catenin proteins in adjacent tissue of breast cancer (n =15),breast hyperplasia tissues (n =25),and breast in vasive ductal carcinoma (n =80).SPSS 17.0 statistical software was used for analysis,such as count data with x2 test and correlation analysis with Spearman test,with significance level of α =0.05.Results The positive rate of Wnt1 and β-catenin in breast cancer group [62.5％ (50/80) and 68.8 (55/80)] was significantly higher than that in hyperplasia group [28％ (7/25) and 20％ (5/25)]and in borderline group [13.33 (2/15) and 13.33 (2/15)] with a significant difference (P ＜ 0.01).Positive expression of Wnt1 and abnormal expression of β-catenin in breast invasive ductal carcinoma were related to lymphatic metastasis (x2 =5.10,4.87,P ＜ 0.05).Abnormal expression of β-catenin was also related to the histological grading of breast invasive ductal carcinoma (x2 =5.61,P ＜ 0.05).The expressions of Wnt1 and β-catenin proteins in invasive ductal carcinoma showed a positive correlation (r =0.313,P ＜ 0.01).Conclusions The high level expression of Wnt1 protein and the abnormal expression of β-catenin protein might play an important role in breast carcinogenesis,and was related to lymph node metastasis.

The Expression and Clinical Significance of DKK1, SFRP4 and Wnt1 in Cervical Squamous Cell Carcinoma / 天津医药

Objective To investigate the expressions of DKK1,SFRP4 and Wnt1 in cervical squamous cell carcino-ma(SCC), and the clinical significance thereof. Methods There were 76 samples of cervical squamous cell carcinoma were included in SCC group and 36 benign uterine resection specimens were control group (NC). The immunohistochemical meth-od was applied to detect the expressions of DKK1,SFRP4 and Wnt1 in two groups. Results The expression of DKK1 was significantly lower in SCC group than that in NC group (P＜0.05). The expression levels of SFRP4 and Wnt1 were significant-ly higher in SCC group than those of NC group (P＜0.05). There were significant differences in the expressions of DKK1, SFRP4 and Wnt1 between samples of different clinical staging, differentiation, sizes of tumor and lymph node metastasis (P＜0.05). The expression of DKK1 was negatively correlated with SFRP4 and Wnt1 in SCC group (P＜0.05). The expression of SFRP4 was positively correlated with Wnt1 in SCC group (P＜0.05). Conclusion The roles of SFRP4 and Wnt1 are syn-ergistic interactions in the development of SCC. DKK1 is an inhibiting factor of SCC.