Wnt/Glycogen Synthase Kinase 3β/β-catenin Signaling Activation Mediated Sevoflurane Preconditioning-induced Cardioprotection

Background:

Sevoflurane preconditioning (SP) has been shown to invoke potent myocardial protection in animal studies and clinical trials. However, the mechanisms underlying SP are complex and not yet well understood. We investigated the hypothesis that the cardioprotection afforded by SP is mediated via the Wnt/glycogen synthase kinase 3β (GSK3β)/β-catenin signaling pathway.

Methods:

Two models were established: A Langendorff perfused rat heart model and the H9C2 cell hypoxia/reoxygenation model. Both rats and H9C2 cells were randomly divided into 6 groups as follows: S group, ischemia-reperfusion (I/R) group, DMSO group, IWP group, SP group, and SP + IWP group. Hemodynamic parameters, lactate dehydrogenase (LDH) activity in coronary effluent and cell culture supernatant, and the infarct size were measured to evaluate myocardial ischemia-reperfusion injuries. To determine the activity of Wnt/GSK3β/β-catenin signaling pathway, the expressions of Wnt3a, phospho-GSK3β, and β-catenin were measured by Western blotting.

Results:

SP improved cardiac function recovery, reduced infarct size (18 ± 2% in the SP group compared with 35 ± 4% in the I/R group; P < 0.05), decreased LDH activity in coronary effluent, and culture supernatant. IWP-2, an inhibitor of Wnt, abolished the cardioprotection by SP. In addition, Western blotting analysis demonstrated that the expressions of Wnt3a, phospho-GSK3β, and β-catenin significantly (P < 0.05) increased in the I/R group, compared with the S group; and compared to I/R group, SP significantly (P < 0.05) increased Wnt3a, phospho-GSK3β, and β-catenin expressions. Pretreatment with IWP-2 significantly (P < 0.05) abolished SP-induced Wnt/GSK3β/β-catenin signaling activation.

Conclusions:

The results showed for the first time that cardioprotection afforded by SP may be mediated partly via the Wnt/GSK3β/β-catenin signaling pathway.     

The expression and clinical sgnificance of Wnt3a, β-catenin and CyclinD1 in gastric carcinoma and gastric ulcers

目的:探讨Wnt3a、β-catenin、CyclinD1在胃癌和胃溃疡组织中的表达及其临床意义.方法:采用免疫组织化学S-ABC法检测48例胃癌组织及42例胃溃疡组织中Wnt3a、β-catenin、CyclinD1的表达及分布.结果:胃癌及胃溃疡组织中均未检测到Wnt3a的表达.β-catenin、CyclinDl在胃癌组织中表达较强,阳性反应与患者的年龄、性别、肿瘤的类型及TNM分期无关,平均光密度值为0.523 ±0.044及0.446±0.054,在胃溃疡组织中阳性反应的平均光密度值为0.367±0.073及0.311±0.029.β-catenin、CyclinD1在胃癌组织的表达明显高于胃溃疡组织,差异有统计学意义(P＜0.05).结论:胃癌组织中β-catenin、CyclinD1的表达明显高于胃溃疡组织,其表达与胃癌患者的年龄、性别、肿瘤的类型及TNM分期无关.     

Effects of Er-Zhi-Wan on Microarchitecture and Regulation of Wnt/β-catenin Signaling Pathway in Alveolar Bone of Ovariectomized Rats简

Recent studies have shown that Er-Zhi-Wan（EZW）, a traditional Chinese medicine consisting of Herba Ecliptae（HE） and Fructus Ligustri Lucidi（FLL）, had a definite antiosteoporotic effect on osteoporotic femur, but its effect on osteoporosis of alveolar bone remains unknown. In the present study, we investigated the effects of Er-Zhi-Wan（EZW） on the microarchitecture and the regulation of Wnt/β-catenin signaling pathway in the alveolar bone of ovariectomized rats. Thirty Sprague-Dawley rats were randomly divided into three groups： sham operation group（sham, n=10）, ovariectomy（OVX） group（n=10）, and OVX with EZW treatment group（EZW group, n=10）. From one week after ovariectomy, EZW（100 mg/mL） or vehicle（distilled water） was fed（1 mL/100 g） once per day for 12 weeks until the sacrifice of the rats. The body weights were measured weekly. After sacrifice, the sera and mandible were collected and routinely prepared for the measurement of alveolar trabecular microarchitecture, serum levels of E2, bone-specific alkaline phosphatase（BALP） and tartrate-resistant acid phosphatase 5b（TRAP5b）, as well as mandibular mRNA expression of Wnt/β-catenin signaling pathway molecules wnt3a, low-density lipoprotein receptor-related protein 5（LRP5）, β-catenin and dickkopf homolog 1（DKK1）. The results showed that EZW treatment significantly prevented the body weight gain, degradation of alveolar trabecular microarchitecture and alveolar bone loss in the OVX rats. Furthermore, we observed that EZW could increase the serum levels of E2 and BALP, and decrease levels of serum TRAP5b in EZW group compared with vehicle group. In addition, RT-PCR results revealed that EZW upregulated the expression levels of wnt3a, LRP5 and β-catenin, and reduced the expression of DKK1 in OVX rats. Taken together, our results suggested that EZW may have potential anti-osteoporotic effects on osteoporotic alveolar bone by stimulating Wnt/LRP5/β-catenin signaling pathway.     

Effect of Berberine on Activation of TLR4-NFκB Signaling Pathway and NLRP3 Inflammasome in Patients with Gout

Objective:To determine the effects of berberine(BBR) on the activation of toll-like receptor 4(ILR4),nuclear factor(NF) κB(NF-κB) signaling and NLRP3 inflammasome in patients with gout.Methods:Peripheral blood mononuclear cells(PBMCs) were obtained from 24 acute(AP) and 41 non-acute(NAP) phases of primary gout patients,respectively,as well as 30 healthy controls(HC).TLR4,NF-κB(p65),NLRP3,apoptosis-associated specklike protein containing a CARD(PYCARD),cysteinyl aspartate specific proteinase-1(CA...     

Effects of Nephritis No.3 Recipe on Nitric Oxide,Nitric Oxide Synthase Secreted by Cultured Mesangial Cells in Rats and the Gene Expression of Inducible Nitric Oxide Synthase

Objective:To explore the effect of the Nephritis No.3(N-3)recipe on nitric oxide(NO),nitric oxide synthase(NOS)secreted by cultured mesangial cells(MC)and its gene expression of the in-ducible nitric oxide synthase(iNOS).Methods:The drug(nephritis No.3)-containing serum was preparedwith serum pharmacological technique,and then was applied to react on mesangial cells cultured In fetalcalf serum(FCS)and cells cultured in FCS plus lipopolysaccharide.To observe the secretion of NO andNOS and the gene expression of iNOS by means of RT-PCR.Results:Under the two kinds of culture con-ditions,the content of NO and NOS in the groups with drug-containing serum were higher than thosewithout drug-containing serum(P<0.05,P<0.01),and the expression of iNOS mRNA was up-regula-ted too.Conclusion:The N-3 could significantly promote the secretion of NO and NOS and the mRNA ex-pression of iNOS in rats.