Microbial imidazole propionate affects glomerular filtration rate in patients with diabetic nephropathy through association with HSP90α.

Imidazole propionate (ImP) is a detrimental metabolite produced by the fermentation of histidine intermediates via the intestinal flora. Here, the untargeted metabolite analysis of plasma metabolites from patients with diabetic nephropathy (DN), in combination with the Human Metabolome Database, revealed significantly increased levels of ImP in patients with DN, with a positive correlation with patients' blood creatinine concentration and urinary albumin-to-creatinine ratio, and a negative correlation with the glomerular filtration rate. RNA-seq was applied to detect the effects of ImP on renal tissue transcriptome in mice with DN. It demonstrated that ImP exacerbated renal injury in mice with DN and promoted renal tubular epithelial-mesenchymal transition (EMT), leading to renal mesenchymal fibrosis and renal impairment. Furthermore, ImP was found to directly target HAP90α and activate the PI3K-Akt signalling pathway, which is involved in EMT, by the drug affinity response target stability method. The findings showed that ImP may provide a novel target for DN quality, as it can directly bind to and activate HSP90, thereby facilitating the development of DN while acting as a potential indicator for the clinical diagnosis of DN.

Sfrp2 promotes renal dysfunction of diabetic kidney disease via modulating Fzd5-induced cytosolic calcium ion concentration and CaMKII/Mek/Erk pathway in mesangial cells.

OBJECTIVE: Mesangial cells (MCs) in the kidney play central role in maintaining glomerular integrity, and their abnormal proliferation leads to major glomerular diseases including diabetic kidney disease (DKD). Although high blood glucose elicits MCs impairment, the underlying molecular mechanism is poorly understood. The present study aimed to investigate the effect of secreted frizzled-related protein 2 (Sfrp2) from single-nucleus RNA profiling on MC proliferation of DKD in vitro and in vivo and explored the specific mechanisms. RESULTS: By snRNA-seq analysis of isolated renal cells from leptin receptor-deficient db/db mice and control db/m mice, we found that Sfrp2 was increased in the MCs of DKD in comparison to other intrinsic renal cells, which was further verified in vitro and in vivo. We also found that the expression of Sfrp2 was significantly upregulated in DKD patients and correlated with renal function, demonstrating that Sfrp2 might serve as an independent biomarker for DKD patients. Functionally, we showed the loss and acquisition of Sfrp2 affected cytosolic Ca2+ concentration, cell proliferation and fibrosis of MC, albuminuria and kidney injury in vitro and in vivo. Mechanistically, we identify c-Jun as a transcription factor of Sfrp2 promoting its transcription, and the Ca2+ signaling related protein frizzled receptor 5 (Fzd5) as the binding protein of Sfrp2. And we further found Sfrp2 promoted Fzd5-induced cytosolic Ca2+ concentration and the downstream CaMKII/Mek/Erk pathway activation, leading to MC proliferation and fibrosis in DKD. CONCLUSION: Our study revealed a novel involvement for Sfrp2 in the regulation of MC function and the effect of Sfrp2 on cell proliferation and fibrosis of MC via the Fzd5/Ca2+/CaMKII/Mek/Erk pathway, implying that Sfrp2 may be a possible biomarker and therapeutic target for DKD.

CircUBXN7 promotes macrophage infiltration and renal fibrosis associated with the IGF2BP2-dependent SP1 mRNA stability in diabetic kidney disease.

Introduction: Inflammatory cell infiltration is a novel hallmark of diabetic kidney disease (DKD), in part, by activated macrophages. Macrophage-to-tubular epithelial cell communication may play an important role in renal fibrosis. Circular RNAs (circRNAs) have been reported in the pathogenesis of various human diseases involving macrophages activation, including DKD. However, the exact mechanism of circRNAs in macrophage infiltration and renal fibrosis of DKD remains obscure. Methods: In our study, a novel circRNA circUBXN7 was identified in DKD patients using microarray. The function of circUBXN7 in vitro and in vivo was investigated by qRT-PCR, western blot, and immunofluorescence. Finally, a dual-luciferase reporter assay, ChIP, RNA pull-down, RNA immunoprecipitation and rescue experiments were performed to investigate the mechanism of circUBXN7. Results: We demonstrated that the expression of circUBXN7 was significantly upregulated in the plasma of DKD patients and correlated with renal function, which might serve as an independent biomarker for DKD patients. According to investigations, ectopic expression of circUBXN7 promoted macrophage activation, EMT and fibrosis in vitro, and increased macrophage infiltration, EMT, fibrosis and proteinuria in vivo. Mechanistically, circUBXN7 was transcriptionally upregulated by transcription factor SP1 and could reciprocally promote SP1 mRNA stability and activation via directly binding to the m6A-reader IGF2BP2 in DKD. Conclusion: CircUBXN7 is highly expressed in DKD patients may provide the potential biomarker and therapeutic target for DKD.

Neuroprotective Effects of Sodium Butyrate by Restoring Gut Microbiota and Inhibiting TLR4 Signaling in Mice with MPTP-Induced Parkinson's Disease.

Parkinson's disease (PD) is a prevalent type of neurodegenerative disease. There is mounting evidence that the gut microbiota is involved in the pathogenesis of PD. Sodium butyrate (NaB) can regulate gut microbiota and improve brain functioning in neurological disorders. Hence, we examined whether the neuroprotective function of NaB on PD was mediated by the modulation of gut microbial dysbiosis and revealed its possible mechanisms. Mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days to construct the PD model. NaB gavage was given 2 h after the daily MPTP injections for 21 days. NaB improved the motor functioning of PD mice, increased striatal neurotransmitter levels, and reduced the death of dopaminergic neurons. The 16S rRNA sequencing analysis revealed that NaB restored the gut microbial dysbiosis. NaB also attenuated the intestinal barrier's disruption and reduced serum, colon, and striatal pro-inflammatory cytokines, along with inhibiting the overactivation of glial cells, suggesting an inhibitory effect on inflammation from NaB throughout the gut-brain axis of the PD mice. Mechanistic studies revealed that NaB treatment suppressed the TLR4/MyD88/NF-kB pathway in the colon and striatum. In summary, NaB had a neuroprotective impact on the PD mice, likely linked to its regulation of gut microbiota to inhibit gut-brain axis inflammation.

Neuroprotective Effects of Sodium Butyrate and Monomethyl Fumarate Treatment through GPR109A Modulation and Intestinal Barrier Restoration on PD Mice.

Research has connected Parkinson's disease (PD) with impaired intestinal barrier. The activation of G-protein-coupled receptor 109A (GPR109A) protects the intestinal barrier by inhibiting the NF-κB signaling pathway. Sodium butyrate (NaB), which is a GPR109A ligand, may have anti-PD effects. The current study's objective is to demonstrate that NaB or monomethyl fumarate (MMF, an agonist of the GPR109A) can treat PD mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) via repairing the intestinal barrier. Male C57BL/6J mice were divided into four groups randomly: control, MPTP + vehicle, MPTP + NaB, and MPTP + MMF. Modeling mice received MPTP (20 mg/kg/day, i.p.) for a week, while control mice received sterile PBS. Then, four groups each received two weeks of sterile PBS (10 mL/kg/day, i.g.), sterile PBS (10 mL/kg/day, i.g.), NaB (600 mg/kg/day, i.g.), or MMF (100 mg/kg/day, i.g.). We assessed the expression of tight junction (TJ) proteins (occludin and claudin-1), GPR109A, and p65 in the colon, performed microscopic examination via HE staining, quantified markers of intestinal permeability and proinflammatory cytokines in serum, and evaluated motor symptoms and pathological changes in the substantia nigra (SN) or striatum. According to our results, MPTP-induced defected motor function, decreased dopamine and 5-hydroxytryptamine levels in the striatum, decreased tyrosine hydroxylase-positive neurons and increased activated microglia in the SN, and systemic inflammation were ameliorated by NaB or MMF treatment. Additionally, the ruined intestinal barrier was also rebuilt and NF-κB was suppressed after the treatment, with higher levels of TJ proteins, GPR109A, and decreased intestinal permeability. These results show that NaB or MMF can remedy motor symptoms and pathological alterations in PD mice by restoring the intestinal barrier with activated GPR109A. We demonstrate the potential for repairing the compromised intestinal barrier and activating GPR109A as promising treatments for PD.

Sp1-Induced lncRNA Rmrp Promotes Mesangial Cell Proliferation and Fibrosis in Diabetic Nephropathy by Modulating the miR-1a-3p/JunD Pathway.

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus. Long non-coding RNAs (lncRNAs) are regulators in DN progression. However, the regulatory mechanisms of multiple lncRNAs in DN remain to be determined. Our aim was to investigate the function and molecular mechanism of lncRNA RNA component of mitochondrial RNAase P (Rmrp) in DN. Here, we observed that the expression of Rmrp was up-regulated in the kidney of db/db DN mice and high glucose induced glomerular mesangial cells (MC). More importantly, the abnormal transcription of Rmrp was induced by nuclear transcription factor Sp1, which promotes the proliferation and production of fibrotic markers in MC. Subsequently, we screened the miRNAs related to Rmrp and found that Rmrp and miR-1a-3p are co-localized at the subcellular level of MC, and Rmrp could directly binds to miR-1a-3p. Further mechanism research demonstrated that the elevated miR-1a-3p significantly attenuated the proliferation and fibrosis-promoting effects induced by up-regulation of Rmrp. At the same time, we also investigated that miR-1a-3p can directly bind to Jun D proto-oncogene (JunD), thereby regulating the protein level of JunD. Rmrp-induced proliferation and fibrogenesis were reversed by co-transfection with JunD siRNA. In summary, Sp1 induced lncRNA Rmrp could drive the expression of JunD via sponging miR-1a-3p in DN progression.

Aqueous Extract of Lysimachia christinae Hance Prevents Cholesterol Gallstone in Mice by Affecting the Intestinal Microflora.

With changes in human dietary patterns, the proportion of high-fat and high-cholesterol foods in the daily diet has increased. As a result, the incidence rate of cholelithiasis is increasing rapidly. Many studies have reported on the crucial role that the intestinal microflora plays in the progression of gallstones. Although the whole herb of Lysimachia christinae, a traditional Chinese medicine, has long been extensively used as a remedy for cholelithiasis in China, its effects on the intestinal microflora remain unknown. Hence, in this study, we investigated the ability of the aqueous extract of L. christinae (LAE) to prevent cholesterol gallstones (CGSs) in model animals by affecting the intestinal microflora. The effects of LAE on body weight, serum lipid profile, visceral organ indexes, and histomorphology were studied in male C57BL/6J mice, which were induced by a lithogenic diet. After the 8-week study, CGSs formation was greatly reduced after LAE treatment. LAE also reduced body weight gain and hyperlipidemia and restored the histomorphological changes. Moreover, the intestinal microflora exhibited significant variation. In the model group fed the lithogenic diet, the abundances of the genera unclassified Porphyromonadaceae, Lactobacillus and Alloprevotella decreased, but in contrast, Akkermansia dramatically increased compared with the control check group, which was fed a normal diet; the administration of LAE reversed these changes. These results imply that L. christinae can be considered an efficient therapy for eliminating CGSs induced by a high-fat and high-cholesterol diet, which may be achieved by influencing the intestinal microflora.

Systematic Identification of Survival-Associated Alternative Splicing Events in Kidney Renal Clear Cell Carcinoma.

There is growing evidence that aberrant alternative splicing (AS) is highly correlated with driving tumorigenesis, but its function in kidney renal clear cell carcinoma (KIRC) remains to be discovered. In this study, we obtained the level-3 RNA sequencing and clinical data of KIRC from The Cancer Genome Atlas (TGCA). Combining with the splicing event detail information from TGCA SpliceSeq database, we established the independent prognosis signatures for KIRC with the univariate and multivariate Cox regression analyses. Then, we used the Kaplan-Meier analysis and receiver operating characteristic curves (ROCs) to assess the accuracy of prognosis signatures. We also constructed the regulatory network of splicing factors (SFs) and AS events. Our results showed that a total of 12029 survival-associated AS events of 5761 genes were found in 524 KIRC patients. All types of prognosis signatures displayed a satisfactory ability to reliably predict, especially in exon skip model which the area under curve of ROC was 0.802. Moreover, 18 splicing factors (SFs) highly correlated to AS events were identified. With the construction of the SF-AS interactive network, we found that SF powerfully promotes the occurrence of abnormal AS and may have a profound role in KIRC. Collectively, we screened survival-associated AS events and established prognosis signatures for KIRC, coupling with the SF-AS interactive network, which might provide a key perspective to clarify the potential mechanism of AS in KIRC.

Potential roles of gut microbiota and microbial metabolites in Parkinson's disease.

Parkinson's disease (PD) is a complicated neurodegenerative disease attributed to multifactorial changes. However, its pathological mechanism remains undetermined. Accumulating evidence has revealed the emerging functions of gut microbiota and microbial metabolites, which can affect both the enteric nervous system and the central nervous system via the microbiota-gut-brain axis. Accordingly, intestinal dysbiosis might be closely associated with PD. This review explores alterations to gut microbiota, correlations with clinical manifestations of PD, and briefly probes the underlying mechanisms. Next, the highly controversial roles of microbial metabolites including short-chain fatty acids (SCFAs), H2 and H2S are discussed. Finally, the pros and cons of the current treatments for PD, including those targeting microbiota, are assessed. Advancements in research techniques, further studies on levels of specific strains and longitudinal prospective clinical trials are urgently needed for the identification of early diagnostic markers and the development of novel therapeutic approaches for PD.

RNA-Seq analysis reveals critical transcriptome changes caused by sodium butyrate in DN mouse models.

Diabetic nephropathy (DN)-a common complication of diabetes-is the primary cause of end-stage renal disease. Sodium butyrate (NaB) is a short-chain fatty acid (SCFA) that is a metabolic product of intestinal bacterium, and its protective effect on the kidney has been reported in cases of DN. However, its underlying mechanism remains unclear. The aim of the present study was to investigate the effect of NaB on globe transcriptome changes in DN. In our study, 8-week-old male db/db mice suffering from DN were randomly divided into two groups: the DN+NaB group (DN mice treated with NaB, 5 g/kg/day) and the DN group (DN mice treated with saline). Further, normal db/m mice were used as the normal control (NC) group. The blood glucose, body weight, urinary microalbumin and urinary creatinine of mice were measured for all three groups. Whole-transcriptome analysis was performed by RNA sequencing (RNA-Seq) to evaluate the profiling of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs). Bioinformatics analysis was performed to predict the potential NaB-related lncRNAs and genes in DN. The expressions of lncRNAs and mRNAs were tested using the quantitative real-time polymerase chain reactions (qRT-PCRs) in renal tissues and mesangial cells treated with NaB. The results of the present study demonstrated that NaB ameliorated renal dysfunction in DN mice. Moreover, RNA-Seq results identified that some lncRNAs and mRNAs were reversely changed in the DN+NaB group in comparison to those in the DN group. Additionally, the integrated co-expression networks of NaB-related lncRNAs revealed that these lncRNAs interacted with 155 key mRNAs. Furthermore, the co-expression network of inflammation-related lncRNAs and mRNAs demonstrated that those reversed lncRNAs and mRNAs also play essential roles in the inflammatory response. In summary, the present study suggests that NaB ameliorates diabetes-induced renal dysfunction and regulates transcriptome changes in DN.

Prevalence and Phylogenetic Analysis of Microsporidium Enterocytozoon bieneusi in Diarrheal Patients.

Enterocytozoon bieneusi can cause severe diarrhea in children and adults. However, in China, there are scant studies on E. bieneusi in diarrheal children and adults, with the exception of prevalence and genotyping data in a small number of cities including Hubei, Shanghai, and Heilongjiang. In this study, 196 fecal samples (n = 132 in Chongqing, n = 44 in Shandong, n = 20 in Hubei) were collected, including 91 from children and 105 from adults. Through microscopic examination, 19 positive samples (11 from children and 8 from adults) were detected. Using PCR examination, the internal transcriptional spacer (ITS) region was utilized by nested PCR to detect and characterize E. bieneusi. Twenty positive samples were detected, including 14 from children (≤11 years of age) and 6 from adults. According to the sequence analysis of ITS data, one known zoonotic (D) and seven novel (CQH5-11) genotypes were identified. This is the first molecular epidemiological study of E. bieneusi in diarrheal patients in different regions of China. Therefore, this study can provide useful information for the molecular epidemiology and control of E. bieneusi infection in humans in the future.

Leveraging sequence-based faecal microbial community survey data to identify alterations in gut microbiota among patients with Parkinson's disease.

Parkinson's disease is a common degenerative disease of the elderly. Although the majority of studies have focused on the central nervous system (CNS) features of Parkinson's disease, recent findings suggest there is a functional link between the gut microbiome and the hallmarks of the disease. PubMed, Web of Science, EMBASE and other Chinese and English databases were searched for relevant literature. Studies on changes to intestinal microbiota in Parkinson's patients were retrieved and systematically reviewed. Quality filtering, clustering and species annotation were performed on 16s sequencing raw data from retrieved studies to achieve comparability across studies. Alpha-diversity indices and a random effect model were used to analyse significantly altered microbiota. A total of nine studies were included in this retrospective analysis, four of which contained raw data. Alpha diversity was significantly different between control and Parkinson's disease patients in two of the four studies. Using the raw data from four individual studies, we observed differences in the phlya Bacteroidetes and Actinobacteria. Additionally, differences were observed between control and Parkinson's disease patients at the level of family (Prevotellacaea and Lactobacillaceae) and genus (Bifidobacterium and Clostridium). This study confirmed that changes in the microbiome are a consistent feature of Parkinson's disease patients and, therefore, may contribute to the onset of disease.

Author Correction: The prevalence of microsporidia in China: A systematic review and meta-analysis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Assessment of the Effectiveness of Vitamin Supplement in Treating Eczema: A Systematic Review and Meta-Analysis.

BACKGROUND: The morbidity of eczema has increased in the recent years, and the methods to prevent or ameliorate its effects are becoming more important. To this end, this research was conducted to determine the effectiveness of vitamin supplements in eczema therapy. METHOD: Embase, PubMed, and Cochrane Central Register of Clinical Trials were searched. Only randomized controlled trials were included, and we included all quantified eligible data where the SCORing Atopic Dermatitis (SCORAD) Index or Eczema Area and Severity Index (EASI) scores were applied to assess the severity of eczema. RESULTS: Ten studies fulfilled the inclusion criteria, and eight of them were included for quantitative analysis (total: 456 patients). Compared to the controls, the SCORAD index or EASI decreased in the vitamin supplement group (mean difference -5.96, 95% CI: -7.69 to -4.23 for vitamin D3; mean difference -5.72, 95% CI: -11.41 to -0.03 for vitamin E; and mean difference -3.19, 95% CI: -4.27 to -2.10 for vitamin B12). CONCLUSION: This study suggests that vitamin supplements could be important therapeutics to help manage eczema patients.

Construction and analysis of a diabetic nephropathy related protein-protein interaction network reveals nine critical and functionally associated genes.

Diabetic nephropathy (DN) is one of the common diabetic complications, but the mechanisms are still largely unknown. In this study, we constructed a DN related protein-protein interaction network (DNPPIN) on the basis of RNA-seq analysis of renal cortices of DN and normal mice, and the STRING database. We analyzed DNPPIN in detail revealing nine critical proteins which are central in DNPPIN, and contained in one network module which is functionally enriched in ribosome, nucleic acid binding and metabolic process. Overall, this study identified nine critical and functionally associated protein-coding genes concerning DN. These genes could be a starting point of future research towards the goal of elucidating the mechanisms of DN pathogenesis and progression.

The topological key lncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathy via the miR-449a/b/Trim11/Mek signaling pathway.

Evidence has shown that long noncoding RNAs (lncRNAs) in the competing endogenous RNA (ceRNA) network are involved in various diseases. However, there is a lack of studies of the ceRNA network in diabetic nephropathy (DN). In this study, we investigated the effect of lncRNAs on mesangial cell (MC) proliferation in DN-related ceRNA networks. Differences in lncRNA and mRNA expression between DN and normal mouse kidney tissues were detected with RNA-seq, and DN-related lncRNA/mRNA/microRNA (miRNA) ceRNA networks were constructed by R3.4.3. Computational analysis was performed, and expression and interactions between the topological RNAs were detected by bioinformatics methods, real-time quantitative PCR (qPCR), and luciferase assay. Cell proliferation ability was measured by 5-ethynyl-2'-deoxyuridine (EdU) in MCs cultured under high- or low-glucose conditions. Moreover, the effect of the topological key lncRNA histocompatibility 2 K region locus 2 (H2k2) H2k2 on MC proliferation via the miRNA (miR)-449a/b/triplet motif 11 (Trim11)/Mek signaling pathway was examined by EdU, flow cytometry analysis, and Western blot. In total, 153 lncRNAs, 428 mRNAs, and 2242 interactions were included in the constructed DN-related ceRNA network. There were 15 RNAs in the top 5% of degree and betweenness. The expression of lncRNA H2k2 and mRNA Trim11 in MCs was increased in DN, which is consistent with the results of RNA-seq and real-time qPCR invivo and in vitro. miR-449a and miR-449b, which were down-regulated in MCs cultured with high glucose, were selected for further analysis. The results of real-time qPCR and luciferase assay revealed the lncRNA H2k2-miR-449a/b-Trim11 interaction in MCs. In addition, the data showed that H2k2 regulates MC proliferation via the miR-449ab/Trim11/Mek signaling pathway. Taken together, these results provide new insight into the association between the topological key lncRNA H2k2 in the DN-related ceRNA network and the miR-449a/b/Trim11/Mek signaling pathway during MC proliferation in DN.-Chen, W., Peng, R., Sun, Y., Liu, H., Zhang, L., Peng, H., Zhang, Z. The topological key lncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathy via the miR-449a/b/Trim11/Mek signaling pathway.

Copper Nanowires Modified with Graphene Oxide Nanosheets for Simultaneous Voltammetric Determination of Ascorbic Acid, Dopamine and Acetaminophen.

Copper nanowires (Cu NWs) were modified with graphene oxide (GO) nanosheets to obtain a sensor for simultaneous voltammetric determination of ascorbic acid (AA), dopamine (DA) and acetaminophen (AC). The nanocomposite was obtained via sonication, and its structures were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and energy-dispersive X-ray spectroscopy (EDS). The electrochemical oxidation activity of the materials (placed on a glassy carbon electrode) was studied by cyclic voltammetry and differential pulse voltammetry. Due to the synergistic effect of Cu NWs and GO, the specific surface, electrochemical oxidation performance and conductivity are improved when compared to each individual component. The peaks for AA (-0.08 V), DA (+0.16 V), and AC (+0.38 V) are well separated. The sensor has wide linear ranges which are from 1-60 µM, 1-100 µM, and 1-100 µM for AA, DA, and AC, respectively, when operated in the differential pulse voltammetric mode. The detection limits are 50, 410 and 40 nM, respectively. Potential interferences by uric acid (20 µM), glucose (10 mM), NaCl (1 mM), and KCl (1 mM) were tested for AA (1 µΜ), DA (1 µΜ), and AC (1 µΜ) and were found to be insignificant. The method was successfully applied to the quantification of AA, DA, and AC in spiked serum samples.

Whole transcriptome analysis of diabetic nephropathy in the db/db mouse model of type 2 diabetes.

Whole-transcriptome analysis using RNA sequencing (RNA-seq) affords broader insights about gene expression regulatory networks in diabetic nephropathy (DN). To better explore the molecular basis of DN, kidney tissue from db/db DN model mice and control mice were submitted to RNA-seq analysis. Thousands of long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) were found to be significantly differentially expressed in the DN group relative to the control group. To research the regulatory mechanism of these lncRNAs and mRNAs, the integrated co-expression networks were constructed for 322 mRNAs and 27 lncRNAs that revealed significantly correlated expression patterns in DN. The potential roles of these co-expressed mRNAs were classified by Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses. The co-expression networks involved 27 lncRNAs interacting with 38 key mRNAs related to metabolic processes, including ND4/4L, Ndufa2/5, Ndufb4/7, Ndufs3, Uqcrc1, Aco2, Alad, Alas1, Alpl, Atp5j2, Coq5, Coq6, Cth, and CytB, all of which are highly related to encoding subunits of the mitochondrial complexes. Thus, mitochondrial dysfunction could result in renal function decline in DN. Seven dysregulated lncRNAs and nine dysregulated mRNAs in the DN model were confirmed by quantitative real-time polymerase chain reaction. The lncRNA-mRNA co-expression network provides novel evidence to support the contention that metabolic changes are associated with metabolic reprogramming in the kidneys, and that these changes play a critical role during the progression of DN.

The prevalence of microsporidia in China : A systematic review and meta-analysis.

Microsporidia are a diverse parasite phylum infecting host from all major taxa in all global biomes. This research was conducted to conclude the prevalence of microsporidia in China. All published articles up to February 16, 2018 were considered, including descriptive, cross-sectional, case-control and epidemiology studies. A total of 1052 articles were separated after literature search. After a strict selection according to our criteria, 82 articles were included in qualitative synthesis and ultimately 52 studies were included in quantitative synthesis. Three species of microsporidia were confirmed to exist in China, including Enterocytozoon bieneusi (E. bieneusi), Nosema and Encephalitozoon cuniculi (E. cuniculi). The highest overall estimated prevalence of E. bieneusi in humans was 8.1%, which was observed in acquired immunodeficiency syndrome patients (AIDS). Moreover, the prevalence of E. bieneusi in animals including the cattle, dogs, pigs, deer, sheep and goats were analyszed in this study. The overall estimated prevalence of E. bieneusi acquired by using the random effects model in meta-analysis in cattle, dogs, pigs, sheep and goats and deer was 20.0% (95% confidence intervals: 0.133-0.266, I2 = 98.031%, p < 0.0001), 7.8% (95% CI: 0.050-0.106, I2 = 60.822%, p = 0.0537), 45.1% (95% CI: 0.227-0.674, I2 = 98.183%, p < 0.0001), 28.1% (95% CI: 0.146-0.415, I2 = 98.716%, p < 0.0001) and 19.3% (95% CI: 0.084-0.303, I2 = 96.995%, p < 0.0001) respectively. The overall detection rate of E. bieneusi in water acquired by using the random effects model in meta-analysis was 64.5% (95% CI: 0.433-0.857, I2 = 98.486%, p < 0.0001). Currently, 221 genotypes of E. bieneusi, 1 genotype of E. cuniculi and 6 Nosema were detected in China. The most prevalent genotype of E. bieneusi was genotype D, followed by BEB6 and EbpC.

The Long Noncoding RNA 150Rik Promotes Mesangial Cell Proliferation via miR-451/IGF1R/p38 MAPK Signaling in Diabetic Nephropathy.

BACKGROUND/AIMS: Diabetic nephropathy (DN) as the primary cause of end-stage kidney disease is a common complication of diabetes. However, the initiating molecular events triggering DN are unknown. Recently, long noncoding RNAs (lncRNAs) have been shown to play important roles in DN. METHODS: The expression level of lncRNA 1500026H17Rik (150Rik for short) was measured by qRT-PCR (quantitative real-time PCR). Cell proliferation ability was detected by 5-Ethynyl-2'-deoxyuridine (EdU). The relationship between 150Rik and microRNA 451 (miR-451) was examined by luciferase assay and RNA immunoprecipitation (RIP) assay. Finally, the effect of 150Rik on cell proliferation through the miR-451/insulin-like growth factor 1 receptor (IGF1R)/mitogen-activated protein kinases (p38MAPK) pathway was detected by EdU, flow cytometry analysis, western blot. RESULTS: We found that 150Rik, an evolutionarily conserved lncRNA, was significantly upregulated in renal tissue of db/db DN mice and in mesangial cells (MCs) cultured under a high glucose condition. Further, overexpression or knockdown of 150Rik was found to regulate cell proliferation in MCs. Moreover, 150Rik was found to interact with miR-451 in both a direct and argonaute-2 (Ago2)-dependent manner. Results also revealed that overexpression of 150Rik inhibited cell proliferation through the miR-451/IGF1R/p38MAPK pathway in MCs under the high glucose condition, while knockdown of 150Rik increased cell proliferation via the miR-451/IGF1R/p38MAPK pathway. CONCLUSION: Taken together, these results provide new insight into the association between 150Rik and the miR-451/IGF1R/p38MAPK signaling pathway during DN progression.