MiR-29b expression is altered in crescent formation of HSPN and accelerates AngⅡ-induced mesangial cell activation

Background MicroRNA-29b(miR-29b)has been suggested to possess pro-inflammatory activity,which can partially be explained by the repression of tumor necrosis factor alpha protein three antibody(TNFAIP3).Meanwhile,it also promotes thyroid cell proliferation via Smad signaling pathways.The present study aimed to elucidate the role of miR-29b in Henoch Sch(o)nlein purpura nephritis(HSPN)and its underlying molecular mechanism in angiotensinⅡ(AngⅡ)-induced human glomerular mesangial cell(HGMC)activation.Methods We evaluated miR-29b expression in 35 HSPN renal tissues based on crescent formation,glomerular sclerosis,interstitial fibrosis,thrombosis formation and capillary loop necrosis.Meanwhile,HGMCs were cultured,treated with AngⅡand then transfected with LV-hsa-miR-29b-1 to induce miR-29b overexpression or LV-hsa-miR-29b-3p-inhibition to inhibit miR-29b expression.Finally,we examined the effects of miR-29b on cell proliferation and release of inflammatory mediators.Results We observed that miR-29b expression was significantly higher in the crescent group than in the no crescent group.MiR-29b overexpression induced the release of intercellular adhesion molecule-1,interleukin-1β(IL-1β),IL-6,IL-8,the increase of CyclinA2,CyclinD 1,and cell proliferation.It also could inhibit the expressions of TNFAIP3 and NF-kappa-B-repressing factor(NKRF).Correspondingly,miR-29b inhibition produced the opposite effects and increased the expression of TNFAIP3 and NKRF.Conclusion MiR-29b expression is altered in crescent formation of HSPN and accelerates AngⅡ-induced mesangial cell proliferation and release of inflammatory mediators.

Heat shock protein 70-2 and tumor necrosis factor-α gene polymorphisms in Chinese children with Henoch- Schönlein purpura

Background:Henoch-Schönlein purpura(HSP)or IgAassociated vasculitis is related to immune disturbances.Polymorphisms of the heat shock protein 70-2 gene(HSP70-2)and the tumor necrosis factor-αgene(TNF-α)are known to be associated with immune diseases.The purpose of this study was to investigate the likely association of HSP70-2(+1267A/G)and TNF-α(+308A/G)gene polymorphisms with HSP in children.Methods:The polymerase chain reaction restriction fragment length polymorphism method was used to detect the HSP70-2 and TNF-αpolymorphisms in 205 cases of children with HSP and 53 controls;and the association of these polymorphisms with HSP and HSP nephritis(HSPN)was analyzed.Results:The G/G genotypic frequencies at the+1267A/G position of HSP70-2 in the HSP group(22.9%)were signifi cantly higher than those in the healthy control group(9.4%)(χ^(2)=4.764,P<0.05).The frequencies of the A/A,A/G and G/G genotypes of HSP70-2 in patients in the nephritis-free group and the HSPN group showed no statistically significant difference.The A/A genotype frequency at the+308G/A position of TNF-αin the HSP group was 8.3%,which was higher than that in the control group(χ^(2)=6.447,P<0.05).The A allele frequency of TNF-αin the HSP group was higher than that in the control group,with a statistically significant difference(χ^(2)=7.241,P<0.05).Conclusions:The HSP70-2(+1267A/G)and TNF-α(+308G/A)gene polymorphisms were associated with HSP in children.The G/G homozygosity of HSP70-2 and the A/A homozygosity of TNF-αmay be genetic predisposing factors for HSP.

Use of off-label nephrology-related drugs in hospitalized pediatric patients: a retrospective study

Background: The information about the use of off-labeldrugs in pediatric nephrology is still lacking, which leadsto increased adverse reactions and medical disputes. Weretrospectively analyzed the use of off-label drugs in thein-patient ward of the nephrology department of NanjingChildren's Hospital, China in order to provide morecomplete information about the use of drugs for children.Methods: Proportional stratified random samplingwas applied to select patients with renal diseases aged 1month to 18 years, who were admitted to the hospital fromOctober 1, 2012 to September 30, 2013. All nephrologyrelateddrugs prescribed in the hospitalization period andtake-home drugs prescribed on discharge were recordedand evaluated as off-label drugs or not from threedifferent perspectives: person-time, prescription, anddrug category.Results: From 385 person-times of patients with 1424prescriptions, according to the ratio between off-labeldrugs and person-times, drug prescriptions, and drugproducts, the rates of off-label drugs were 40.78%, 16.64%,and 31.43%, respectively. Low-molecular-weight heparin,alfacalcidol and diltiazem were the most commonly usedoff-label drugs. Infants and younger children were thehigh-risk population of off-label drug use. The high rateoff-label nephrology-related drug use in children wasmainly related to lacking clinical research into drugs inchildren and the pace of drug label's revision, which cannotfollow the development of medical science.Conclusions: Approximaely half of pediatric patientswith renal diseases are usually prescribed with off-labelnephrology-related drugs. Analyzing the off-label conditionsfrom different perspectives may lead to various results.More clinical research into drugs for infants and youngerchildren is needed so as to update drug descriptions.