Non-linear relationship between body roundness index and albuminuria among children and adolescents aged 8-19 years: A cross-sectional study.

INTRODUCTION: Obesity has been found to be correlated with numerous health issues, including an elevated risk of albuminuria in adults. However, this correlation is still controversial among children and adolescents, as several recent large-scale cross-sectional studies have observed a negative correlation between obesity and albuminuria. Our study aimed to investigate the link between the body roundness index (BRI) and albuminuria among children and adolescents, in order to further understand the correlation between obesity and albuminuria in this demographic. METHODS: We employed information from the National Health and Nutrition Examination Survey (NHANES) 1999-2010 for cross-sectional analysis. Weighted logistic regression was employed to explore the linear relationship between BRI and albuminuria, with subgroup analyses performed for more detailed insights. Weighted linear regression analysis was employed to explore the relationship between BRI and the urine albumin-creatinine ratio (UACR). Additionally, we applied smooth curve fitting to investigate their non-linear relationship and conducted threshold effect analysis to identify any turning point. RESULTS: In this study of 15,487 participants aged 8-19 years, multivariate logistic regression analysis revealed a significant negative correlation between BRI and albuminuria (OR = 0.616, 95%CI: 0.526-0.722). The relationship between BRI and UACR, as shown by multivariate linear regression analysis, was significantly inversely correlated (ß: -5.424, 95%CI: -7.416 to -3.433). Furthermore, smooth curve fitting and threshold effect analysis showed a non-linear relationship between BRI and albuminuria, with a BRI inflection point identified at 2.906. CONCLUSIONS: These findings of our study suggest a significant nonlinear negative association between BRI and the presence of albuminuria among children and teenagers, and maintaining an appropriate BRI may decrease the occurrence of albuminuria in this population.

The association between appendicular skeletal muscle index and bone mineral density in children and adolescents with chronic kidney disease: A cross-sectional study.

Chronic kidney disease (CKD), a pervasive public health concern, can lead to complications like sarcopenia and reduced bone mineral density (BMD). However, it is still unclear exactly how muscle mass correlates with BMD in youngsters and adolescents with CKD. We aimed to investigate the association between appendicular skeletal muscle index (ASMI) and BMD among children and adolescents with CKD. In our research, we utilized data from the National Health and Nutrition Examination Survey (NHANES) collected between 2011 and 2014 to investigate the association of ASMI with BMD among this population. The association linking ASMI with total BMD was examined through multivariate linear regression models. Furthermore, fitted smoothing curves were employed, as well as generalized additive models. Our analysis finally included 503 CKD participants aged between 8 and 19 years. We found a significant association linking ASMI with total BMD among children and adolescents with CKD. The connection persisted even after accounting for covariates. Upon subgroup analysis, there was a statistically significant association of ASMI with total BMD for both males and females, as well as for Mexican-American and non-Hispanic White populations. However, no significant association was observed in other Hispanic, non-Hispanic Black, or populations of other races. We discovered a positive correlation linking the ASMI and the total BMD in children and teenagers with CKD. In CKD patients, maintaining skeletal muscle mass may be crucial for managing and preventing renal osteodystrophy.

DNase I targeted degradation of neutrophil extracellular traps to reduce the damage on IgAV rat.

BACKGROUND: In the past two years, studies have found a significant increase in neutrophil extracellular traps (NETs) in patients with IgA vasculitis (IgAV), which is correlated with the severity of the disease. NETs have been reported as an intervention target in inflammatory and autoimmune diseases. This study aimed to investigate the effect of targeted degradation of NETs using DNase I in IgAV rat model. METHODS: Twenty-four Sprague-Dawley rats were randomly divided into three groups: the IgAV model group, the DNase I intervention group and the normal control group, with an average of 8 rats in each group. The model group was established by using Indian ink, ovalbumin, and Freund's complete adjuvant. In the intervention group, DNase I was injected through tail vein 3 days before the end of established model. The circulating cell free-DNA (cf-DNA) and myeloperoxidase-DNA (MPO-DNA) were analyzed. The presence of NETs in the kidney, gastric antrum and descending duodenum were detected using multiple fluorescences immunohistochemistry and Western blots. Morphological changes of the tissues were observed. RESULTS: After the intervention of DNase I, there was a significant reduction in cf-DNA and MPO-DNA levels in the intervention group compared to the IgAV model group (all P<0.001). The presence of NETs in renal, gastric, and duodenal tissues of the intervention group exhibited a significant decrease compared to the IgAV model group (P < 0.01). Moreover, the intervention group demonstrated significantly lower levels of renal MPO and citrullinated histone H3 (citH3) protein expression when compared to the IgAV model group (all P < 0.05). The HE staining results of intervention group demonstrated a significant reduction in congestion within glomerular and interstitial capillaries. Moreover, there was a notable improvement in gastric and intestinal mucosa necrosis, congestion and bleeding. Additionally, there was a substantial decrease in inflammatory cells infiltration. CONCLUSION: The degradation of NETs can be targeted by DNase I to mitigate tissue damage in IgAV rat models. Targeted regulation of NETs holds potential as a therapeutic approach for IgAV.

Expression of GADD45B in Renal Tissue of Children with IgA Nephropathy and Correlation with Mesangial Hypercellularity.

Background: We correlated the expression of growth arrest and DNA damage-inducible protein beta (GADD45B) in renal tissue with IgA nephropathy (IgAN) with clinical characteristics and mesangial hypercellularity. Materials and methods: Biopsies from IgAN children were divided into M0 and M1 groups based on the Oxford classification, and biopsies with minimal change disease (MCD) were selected as controls. The mesangial cell proliferation area was evaluated on PAS-stained tissues, and the relative level of GADD45B in renal tissue was assessed by immunohistochemical staining (IHC). Results: Compared with the MCD group, levels of GADD45B in the M0 and M1 groups were significantly higher (p < 0.05). Levels of GADD45B positively correlated with mesangial cell proliferation, proteinuria, and total cholesterol, negatively correlated with Alb levels. Conclusions: It is suggested that high expression of GADD45B may play a regulatory role in mesangial hypercellularity.

Neutrophil extracellular traps involved in the pathogenesis of IgA vasculitis: Confirmed in two IgAV rat models.

BACKGROUND: Neutrophil extracellular traps (NETs) have been found to play a role in the development of autoimmune diseases. In the past two years, studies have demonstrated a significantly increase of NETs in skin tissues during the early stages of IgAV, indicating their involvement in disease activity among children with IgAV. However, the presence of NETs in IgAV animal models has not yet been reported. The objective of this study is to investigate whether NETs are involved in the pathogenesis of IgA vasculitis (IgAV) rats. METHODS: Twenty-four SD rats were randomly divided into three groups: the ovalbumin group, the gliadin group, and the control group. The IgAV rat models were established administering Indian ink with ovalbumin (ovalbumin group) or gliadin (gliadin group) with Freund's complete adjuvant. The cell-free DNA (cf-DNA) was quantified by using dsDNA quantification kit, while the levels of Immunoglobulins, complement C3 and myeloperoxidase-DNA (MPO-DNA) in serum were tested using enzyme linked immunosorbent assay (ELISA). The IgA, complement C3 and NETs in tissues were detected through multiple immunofluorescences. RESULTS: Both the ovalbumin group and gliadin group showed IgA and C3 deposition in various tissues, including the glomerular mesangial region, skin, and digestive tract, while the control group showed no such deposition. The levels of circulatory cf-DNA and MPO-DNA, which are components of NETs, were significantly elevated in both ovalbumin and gliadin groups compared with the control group. Furthermore, the presence of NETs were found in gastrointestinal and renal tissues of the ovalbumin and gliadin groups, but not in the control group. CONCLUSIONS: IgAV model rat can be established through the combination of ovalbumin and gliadin with Indian ink and Freund's complete adjuvant. This study provides the first confirmation that NETs are involved in the pathogenesis of IgAV rat.

Hypobaric Hypoxia Aggravates Renal Injury by Inducing the Formation of Neutrophil Extracellular Traps through the NF-κB Signaling Pathway.

OBJECTIVE: The hypersensitivity of the kidney makes it susceptible to hypoxia injury. The involvement of neutrophil extracellular traps (NETs) in renal injury resulting from hypobaric hypoxia (HH) has not been reported. In this study, we aimed to investigate the expression of NETs in renal injury induced by HH and the possible underlying mechanism. METHODS: A total of 24 SD male rats were divided into three groups (n=8 each): normal control group, hypoxia group and hypoxia+pyrrolidine dithiocarbamate (PDTC) group. Rats in hypoxia group and hypoxia+PDTC group were placed in animal chambers with HH which was caused by simulating the altitude at 7000 meters (oxygen partial pressure about 6.9 kPa) for 7 days. PDTC was administered at a dose of 100 mg/kg intraperitoneally once daily for 7 days. Pathological changes of the rat renal tissues were observed under a light microscope; the levels of serum creatinine (SCr), blood urea nitrogen (BUN), cell-free DNA (cf-DNA) and reactive oxygen species (ROS) were measured; the expression levels of myeloperoxidase (MPO), citrullinated histone H3 (cit-H3), B-cell lymphoma 2 (Bcl-2), Bax, nuclear factor kappa B (NF-κB) p65 and phospho-NF-κB p65 (p-NF-κB p65) in rat renal tissues were detected by qRT-qPCR and Western blotting; the localization of NF-κB p65 expression in rat renal tissues was observed by immunofluorescence staining and the expression changes of NETs in rat renal tissues were detected by multiplex fluorescence immunohistochemical staining. RESULTS: After hypoxia, the expression of NF-κB protein in renal tissues was significantly increased, the levels of SCr, BUN, cf-DNA and ROS in serum were significantly increased, the formation of NETs in renal tissues was significantly increased, and a large number of tubular dilatation and lymphocyte infiltration were observed in renal tissues. When PDTC was used to inhibit NF-κB activation, NETs formation in renal tissue was significantly decreased, the expression level of Bcl-2 in renal tissues was significantly increased, the expression level of Bax was significantly decreased, and renal injury was significantly alleviated. CONCLUSION: HH induces the formation of NETs through the NF-κB signaling pathway, and it promotes apoptosis and aggravates renal injury by decreasing Bcl-2 and increasing Bax expression.

Case report: Two cases of Poirier-Bienvenu neurodevelopmental syndrome and review of literature.

The Poirier-Bienvenu neurodevelopmental syndrome (POBINDS) is a rare disease caused by mutations in the CSNK2B gene, which is characterized by intellectual disability and early-onset epilepsy. Mosaicism has not been previously reported in CSNK2B gene. POBINDS is autosomal dominant and almost all reported cases were de novo variants. Here, we report two patients were diagnosed with POBINDS. Using Whole Exome Sequencing (WES), we detected two novel CSNK2B variants in the two unrelated individuals: c.634_635del (p.Lys212AspfsTer33) and c.142C > T (p.Gln48Ter) respectively. Both of them showed mild developmental delay with early-onset and clustered seizures. The patient with c.634_635del(p.Lys212AspfsTer33) variant was mutant mosaicism, and the proportion of alleles in peripheral blood DNA was 28%. Further, the literature of patients with a de novo mutation of the CSNK2B gene was reviewed, particularly seizure semiology and genotype-phenotype correlations.

Identification of AGXT2, SHMT1, and ACO2 as important biomarkers of acute kidney injury by WGCNA.

Acute kidney injury (AKI) is a serious and frequently observed disease associated with high morbidity and mortality. Weighted gene co-expression network analysis (WGCNA) is a research method that converts the relationship between tens of thousands of genes and phenotypes into the association between several gene sets and phenotypes. We screened potential target genes related to AKI through WGCNA to provide a reference for the diagnosis and treatment of AKI. Key biomolecules of AKI were investigated based on transcriptome analysis. RNA sequencing data from 39 kidney biopsy specimens of AKI patients and 9 normal subjects were downloaded from the GEO database. By WGCNA, the top 20% of mRNAs with the largest variance in the data matrix were used to construct a gene co-expression network with a p-value < 0.01 as a screening condition, showing that the blue module was most closely associated with AKI. Thirty-two candidate biomarker genes were screened according to the threshold values of |MM|≥0.86 and |GS|≥0.4, and PPI and enrichment analyses were performed. The top three genes with the most connected nodes, alanine-glyoxylate aminotransferase 2(AGXT2), serine hydroxymethyltransferase 1(SHMT1) and aconitase 2(ACO2), were selected as the central genes based on the PPI network. A rat AKI model was constructed, and the mRNA and protein expression levels of the central genes in the model and control groups were verified by PCR and immunohistochemistry experiments. The results showed that the relative mRNA expression and protein levels of AGXT2, SHMT1 and ACO2 showed a decrease in the model group. In conclusion, we inferred that there is a close association between AGXT2, SHMT1 and ACO2 genes and the development of AKI, and the down-regulation of their expression levels may induce AKI.

Rosiglitazone attenuates hypoxia-induced renal cell apoptosis by inhibiting NF-κB signaling pathway in a PPARγ-dependent manner.

BACKGROUND: In recent years, peroxisome proliferator-activated receptor γ (PPARγ) has been found to be closely associated with hypoxia renal disease. The aim of this study was to investigate the relationship between rosiglitazone and mitochondrial apoptosis in renal tissue and its associated mechanisms. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into three groups (n = 8 in each): normal control group, hypoxia injury group (equal volume of 0.9% saline), and PPARγ agonist group (Rosiglitazone, 10 mg/kg · d, intraperitoneally). The hypoxia injury group and PPARγ agonist group were placed in a hypoxia chamber and the simulated altitude was set at 7,000 m for 7 days. Blood and kidney samples were collected after 7 days. The quantitative real-time polymerase chain reaction and Western blot methods were used to determine the expression of PPARγ, nuclear factor kappa-B (NF-κB), B-cell lymphoma-2 (Bcl-2), and Bax. RESULTS: The results showed that compared with the normal control group, the renal tissue of rats after hypoxia was severely damaged, as shown by massive renal tubular epithelial cell degeneration and detachment, and renal tubular dilation. The NF-κB protein expression significantly increased, the Bcl-2 protein and mRNA expression significantly decreased, and Bax protein and mRNA expression significantly increased (p < .05 for all). Renal injury was much less severe in the PPARγ agonist group compared to the hypoxia injury group. CONCLUSIONS: Rosiglitazone can alleviate hypoxia renal injury, with the possible mechanism involving attenuation of apoptosis by inhibiting the activation of the NF-κB signaling pathway in a PPARγ-dependent manner and increasing Bcl-2 and decreasing Bax expression.

Study of Texture Indicators Applied to Pavement Wear Analysis Based on 3D Image Technology.

Pavement texture characteristics can reflect early performance decay, skid resistance, and other information. However, most statistical texture indicators cannot express this difference. This study adopts 3D image camera equipment to collect texture data from laboratory asphalt mixture specimens and actual pavement. A pre-processing method was carried out, including data standardisation, slope correction, missing value and outlier processing, and envelope processing. Then the texture data were calculated based on texture separation, texture power spectrum, grey level co-occurrence matrix, and fractal theory to acquire six leading texture indicators and eight extended indicators. The Pearson correlation coefficient was used to analyse the correlation of different texture indicators. The distinction vector based on the information entropy is calculated to analyse the distinction of the indicators. High correlations between ENE (energy) and ENT (entropy), ENT and D (Minkowski dimension) were found. The CON (contrast) has low correlations with HT (macro-texture power spectrum area), ENT and D. However, the differentiation of ENE and HT is more prominent, and the differentiation of the CON is smaller. ENE, ENT, CON and D indicators based on macro-texture and the corresponding original texture have strong linear correlations. However, the microtexture indicators are not linearly correlated with the corresponding original texture indicators. D, WT (micro-texture power spectrum area) and ENT exhibit high degrees of numerical concentration for the same road sections and may be more statistically helpful in distinguishing the characteristics of the pavement performance decay of the road sections.

An Emerging Role for Neutrophil Extracellular Traps in IgA Vasculitis: A Mini-Review.

Immunoglobulin A vasculitis (IgAV) is the most common systemic small vessel vasculitis in childhood. Its clinical manifestations are non-thrombocytopenic purpura, accompanied by gastrointestinal tract, joint, kidney and other organ system involvement. The pathogenesis of IgAV has not been fully elucidated. It may be related to many factors including genetics, infection, environmental factors, and drugs. The most commonly accepted view is that galactose-deficient IgA1 and the deposition of IgA and complement C3 in small blood vessel walls are key contributors to the IgAV pathogenesis. Extensive neutrophil extracellular traps (NETs) in the peripheral circulation and skin, kidney, and gastrointestinal tissue of patients with IgAV has been identified in the past two years and is associated with disease activity. This mini-review provides a possible mechanism for NETs involvement in the pathogenesis of IgAV.

The Clinical and Genetic Features in Chinese Children With Steroid-Resistant or Early-Onset Nephrotic Syndrome: A Multicenter Cohort Study.

Steroid-resistant nephrotic syndrome (SRNS) is one of the major causes of end-stage kidney disease (ESKD) in children and young adults. For approximately 30% of children with SRNS results from a genetic cause. In this study, genotype-phenotype correlations in a cohort of 283 pediatric patients with SRNS or early-onset NS (nephrotic syndrome presenting within the first year of life) from 23 major pediatric nephrology centers in China were analyzed. All patients were performed with next-generation sequencing and Sanger sequencing. The overall mutation detection rate was 37.5% (106 of 283 patients). WT1 was the most frequently detected mutation, followed by NPHS1, NPHS2, and ADCK4, and these four major causative genes (WT1, NPHS1, NPHS2, and ADCK4) account for 73.6% of patients with monogenic SRNS. Thirteen of 106 individuals (12.3%) carried mutations in ADCK4 that function within the coenzyme Q10 biosynthesis pathway. In the higher frequently ADCK4-related SRNS, two mutations, c.737G>A (p.S246N) and c.748G>C (p.D250H), were the most prevalent. Our study provides not only definitive diagnosis but also facilitate available targeted treatment for SRNS, and prediction of prognosis and renal outcome. Our indications for genetic testing are patients with FSGS, initial SRNS, cases of positive family history or those with extra-renal manifestations.

Proteomic analysis of serum proteins in children with brain death.

BACKGROUND: Brain death (BD) is a catastrophic physiological outcome that can occur in individuals with terminal illness and can adversely affect the graft quality after donation of their organs. As BD has no specific symptoms, it can be difficult to diagnose in a timely manner. The present study was designed to investigate the serum protein expression profiles of children affected by BD in an effort to define diagnostic biomarkers for this condition. METHODS: Blood samples were collected from 8 patients with BD and 8 healthy controls during the same time period. Tandem mass tags and mass spectrometry were used to conduct a proteomic analysis of serum extracted from the samples. The potential regulatory roles of the top 5 upregulated and downregulated proteins identified through the analysis were then explored using bioinformatics analyses and a review of the related literature. RESULTS: The top 5 upregulated proteins in the serum samples from patients with BD were lipopolysaccharide-binding protein (LBP), α1-acid glycoprotein (α1-AGP), α1-antichymotrypsin (α1-ACT), leucine-rich α1-glycoprotein (LRG1), and lactate dehydrogenase B heavy chain (LDHB), and the 5 most downregulated proteins in these samples were actin-binding protein 2 (transgelin-2), platelet basic protein (PBP), tropomyosin α4 chain (TPM4), tropomyosin α3 chain (TPM3), and peptidase inhibitor 16 (PI16). Literature searches indicated that several of the identified proteins influence the pathogeneses of various diseases, with LBP, α1-AGP, α1-ACT, LRG1, transgelin-2, and PBP all being related to inflammatory activity. CONCLUSIONS: Through a proteomics-based analysis, several differentially expressed proteins were identified in patients with BD relative to healthy controls. Most of these proteins are associated with inflammatory responses that have the potential to persist after the occurrence of BD. Further clinical work is needed to clarify the functional roles of the identified proteins.

The important roles and molecular mechanisms of annexin A2 autoantibody in children with nephrotic syndrome.

BACKGROUND: In recent years, B-cell dysfunction has been found to play an important role in the pathogenesis of primary nephrotic syndrome (PNS). B cells play a pathogenic role by secreting antibodies against their target antigens after transforming into plasma cells. Therefore, this study aimed to screen the autoantibodies that cause PNS and explore their pathogenic mechanisms. METHODS: Western blotting and mass spectrometry were employed to screen and identify autoantibodies against podocytes in children with PNS. Both in vivo and in vitro experiments were used to study the pathogenic mechanism of PNS. The results were confirmed in a large multicenter clinical study in children. RESULTS: Annexin A2 autoantibody was highly expressed in children with PNS with a pathological type of minimal change disease (MCD) or focal segmental glomerulosclerosis without genetic factors. The mouse model showed that anti-Annexin A2 antibody could induce proteinuria in vivo. Mechanistically, the effect of Annexin A2 antibody on the Rho signaling pathway was realized through promoting the phosphorylation of Annexin A2 at Tyr24 on podocytes by reducing its binding to PTP1B, which led to the cytoskeletal rearrangement and damage of podocytes, eventually causing proteinuria and PNS. CONCLUSIONS: Annexin A2 autoantibody may be responsible for some cases of PNS with MCD/FSGS in children.

Identification and Validation of a Dysregulated miRNA-Associated mRNA Network in Temporal Lobe Epilepsy.

OBJECTIVES: This study is aimed at exploring the relationships between miRNAs and mRNAs and to characterize their biological functions in temporal lobe epilepsy (TLE). METHODS: Novel clinical significant miRNAs and target genes and their potential underlying mechanisms have been discovered and explored by mining miRNAs and mRNA expression data of TLE patients using various bioinformatics methods. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to validate the bioinformatic analysis results. RESULTS: A total of 6 dysregulated miRNAs and 442 differentially expressed genes (DEGs) related to TLE were obtained from GEO database (GSE114701 and GSE127871 datasets). A protein-protein interaction (PPI) network containing the 442 DEGs was established. mRNA response elements from the 6 dysregulated miRNAs were predicted using the miRDB and TargetScan bioinformatic tools. By merging the identified targets of the dysregulated miRNAs and the 247 downregulated DEGs, a miRNA-mRNA network was constructed revealing the interaction of miR-484 with eight mRNAs (ABLIM2, CEP170B, CTD-3193O13.9, EFNA5, GAP43, PRKCB, FXYD7, and NCAN). A weighted correlation network analysis (WGCNA) based on the eight genes was established and demonstrated that these mRNAs, except FXYD7 and NCAN, were hub genes in the network. Gene Oncology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that the six hub genes were mainly involved in cellular-related biological functions and the neurotransmitter synapse pathway. The differences in expression levels of the miR-484 and the three hub genes (CTD-3193O13.9, EFNA5, and PRKCB) observed experimentally in TLE patients compared to those of healthy controls were consistent with the WGCNA prediction. CONCLUSION: Our study suggests that understanding the miRNA-mRNA interactions will provide insights into the epilepsy pathogenesis. In addition, our results indicate that miR-484 may be a promising novel biomarker for TLE.

The Involvement of Neutrophil Extracellular Traps in Disease Activity Associated With IgA Vasculitis.

Objectives: This aim of this study was to determine whether neutrophil extracellular traps (NETs) are involved in the pathogenesis of IgA vasculitis (IgAV) and investigate whether the circulating NETs levels are associated with disease activity in children. Methods: We performed a case-control study and collected blood samples from 193 children with different stages of IgAV (61 were at the onset stage, 64 at the remission stage, 43 at the active stage, and 25 were undergoing drug withdrawal). A total of 192 healthy children were recruited as controls. Circulating cell free DNA (cf-DNA) was obtained from the plasma and quantified by using the Quant-iT PicoGreen DNA quantification kit. NETs-associated myeloperoxidase-DNA (MPO-DNA), citrullinated-histone H3 (cit-H3), neutrophil elastase (NE), and the deoxyribonuclease I (DNase I) concentrations were measured using enzyme-linked immunosorbent assays. The presence of NETs in the kidney and gastrointestinal tissues of onset and active IgAV patients was determined by multiple immunofluorescence staining in 15 IgAV nephritis patients and 9 IgAV patients without IgAV nephritis, respectively. NETs degradation potency of collected sera samples from IgAV patients were checked in vitro. Relationships between circulating levels of cf-DNA with MPO-DNA, NE, and DNase I and the patients were analyzed. Results: Circulating levels of cf-DNA in onset and active IgAV patients were significantly higher than those in remission and drug withdrawal patients as well as healthy controls. The results were similar for MPO-DNA and NE. The levels of circulating cf-DNA correlated significantly with MPO-DNA, NE and DNase I. A significantly decreased degradation of NETs from the onset and active IgAV patients was observed, but was normal in healthy controls. Furthermore, presence of NETs was also confirmed in all renal and gastrointestinal tissues obtained from the onset and active IgAV patients but not control samples. Conclusions: Our data showed that NETs were released into the circulation of IgAV patients and are involved in the disease activity. The circulating levels of NETs maybe used to assess disease severity in children with IgAV.

PPARγ and mitophagy are involved in hypoxia/reoxygenation-induced renal tubular epithelial cells injury.

Renal tubular epithelial cell (RTEC) injury is the main cause and common pathological process of various renal diseases. Mitochondrial dysfunction (MtD) is a pathological process after renal injury. Mitophagy is vital for mitochondrial function. Hypoxia is a common cause of RTEC injury. Peroxisome proliferator-activated receptor γ (PPARγ) is involved in cell proliferation, apoptosis, and inflammation. Previous studies have shown that the low expression of PPARγ might be involved in hypoxia-induced RTEC injury. The present study aimed to investigate the correlation between PPARγ and mitophagy in damaged RTEC in the hypoxia/reoxygenation (HR) model. The results showed that HR inhibited the expression of PPARγ, but increased the expression of LC3II, Atg5, SQSTM1/P62, and PINK1 in a time-dependent manner. Moreover, mitochondrial DNA (mt DNA) copy number, mitochondria membrane potential (MMP) levels, ATP content, and cell viability were decreased in hypoxic RTECs, the expression of SQSTM1/P62 and PINK1, the release of cytochrome c (cyt C), and production of reactive oxygen species (ROS) were increased. Mitochondrial-containing autophagosomes (APs) were detected using transmission election microscope (TEM) and laser scanning confocal microscope (LSCM). Furthermore, PPARγ protein expression was negatively correlated with that of LC3II, PINK1, and the positive rate of RTEC-containing mitochondrial-containing APs (all p < .05), but positively correlated with cell viability, MMP level, and ATP content (all p < .05). These data suggested that PPARγ and mitophagy are involved in the RTEC injury process. Thus, a close association could be detected between PPARγ and mitophagy in HR-induced RTEC injury, albeit additional investigation is imperative.

Effectiveness and Safety of Deferasirox in Thalassemia with Iron Overload: A Meta-Analysis.

Deferasirox (DFX) has recently been used to treat thalassemia with iron overload; however, its long-term effectiveness and safety await multi-year studies. In this study, a systematic meta-analysis was performed to assess the effectiveness and safety of DFX in the treatment of thalassemia with iron overload. We performed a systematic electronic literature search for randomized controlled studies of DFX in the Embase, Medline, Cochrane, and Chinese Biomedical Literature (CBM) databases from January 1990 to May 2018. Particular attention was paid to mortality, serum ferritin (SF), liver iron concentration (LIC), myocardial iron concentration, and adverse events (AEs). Six studies comparing DFX with deferoxamine (DFO) and placebo were enrolled. DFX was not better than DFO in lowering SF and LIC, with an exception that high DFX dose (> 30 mg/kg/day) was superior to DFO in LIC. Otherwise, AEs such as gastrointestinal problems appeared to be more common with DFX. DFX does not seem to be superior to DFO at low dose. Similar efficacy seems to be achievable depending on dose. However, the convenient oral administration of DFX has a higher compliance rate.

Protective effect of retinoic acid receptor α on hypoxia-induced epithelial to mesenchymal transition of renal tubular epithelial cells associated with TGF-ß/MMP-9 pathway.

Retinoic acid receptor α (RARα), a member of family of the nuclear retinoic acid receptors (RARs), plays an essential role in various chronic kidney diseases (CKD). Renal tubular epithelial to mesenchymal transition (EMT) is a common mechanism of progression of renal interstitial fibrosis (RIF). Hypoxia has been extensively considered as one of major inducers of renal tubular EMT. However, the effects of RARα on hypoxia-induced EMT have not yet been described so far. The aim of the present study was to explore the roles and potential mechanisms of RARα in hypoxia-induced EMT of renal tubular epithelial cells (RTECs). Our results showed that expression of RARα in RTECs subjected to hypoxia significantly was reduced, accompanied by decreased expression level of the epithelial marker E-cadherin, and increased expression levels of the mesenchymal markers α-smooth muscle actin (α-SMA) and vimentin, in accord with EMT. Meanwhile, hypoxia could cause RTECs to obviously express TGF-ß and matrix metalloproteinase-9 (MMP-9). Furthermore, using lentivirus-based delivery vectors to overexpress RARα in RTECs, we demonstrated that RARα alleviated hypoxia-induced EMT of RTECs and downregulated the expression levels of TGF-ß and MMP-9. In a word, RARα protects RTECs against EMT induced by hypoxia associated with TGF-ß/MMP-9 pathway.

ATRA attenuate proteinuria via downregulation of TRPC6 in glomerulosclerosis rats induced by adriamycin.

OBJECTIVE: In this research, we explored the molecular mechanism of proteinuria in glomerulosclerosis rats and the protective effects of ATRA. METHODS: This research set up three groups: SHO group, GS group, and ATRA group (15 mg/(kg d), Sigma, St. Louis, MO). The serum creatinine (Scr), urea nitrogen (BUN), and 24-h proteinuria were detected 12 weeks after administration of ATRA. The pathological and ultrastructure changes were observed under light microscope and transmission electron microscope. The protein expression of TGF-ß1 and Col-IV in glomerulus was detected by immunohitochemistry method. The mRNA and the protein expression of glomerular TRPC6 were detected by RT-PCR and Western blot. RESULTS: In the rat model of GS, the expressions of TRPC6 were significantly elevated compared with the normal rat group; however, the use of ATRA down-regulated the expression of TRPC6 in the glomeruli and attenuated glomerulosclerosis and proteinuria. Scr and BUN were also improved by the treatment of ATRA. CONCLUSIONS: Our results demonstrated that ATRA could ameliorate glomerulosclerosis and proteinuria in GS, which may be related to suppressed expression of TRPC6.