Four novel mutations identified in the COL4A3, COL4A4 and COL4A5 genes in 10 families with Alport syndrome.

BACKGROUND: Alport syndrome (AS) is an inherited nephropathy caused by mutations in the type IV collagen genes. It is clinically characterized by damage to the eyes, ears and kidneys. Diagnosis of AS is hampered by its atypical clinical picture, particularly when the typical features, include persistent hematuria and microscopic changes in the glomerular basement membrane (GBM), are the only clinical manifestations in the patient. METHODS: We screened 10 families with suspected AS using whole exome sequencing (WES) and analyzed the harmfulness, conservation, and protein structure changes of mutated genes. In further, we performed in vitro functional analysis of two missense mutations in the COL4A5 gene (c.2359G > C, p.G787R and c.2605G > A, p.G869R). RESULTS: We identified 11 pathogenic variants in the type IV collagen genes (COL4A3, COL4A4 and COL4A5). These pathogenic variants include eight missense mutations, two nonsense mutations and one frameshift mutation. Notably, Family 2 had digenic mutations in the COL4A3 (p.G1170A) and UMOD genes (p.M229K). Family 3 had a digenic missense mutation (p.G997E) in COL4A3 and a frameshift mutation (p.P502L fs*151) in COL4A4. To our knowledge, four of the 11 mutations are novel mutations. In addition, we found that COL4A5 mutation relation mRNA levels were significantly decreased in HEK 293 T cell compared to control, while the cellular localization remained the same. CONCLUSIONS: Our research expands the spectrum of COL4A3-5 pathogenic variants, which is helpful for clinical and scientific research.

Identification of a novel nonsense mutation in α-galactosidase A that causes Fabry disease in a Chinese family.

Fabry disease, a lysosomal storage disease, is an uncommon X-linked recessive genetic disorder stemming from abnormalities in the alpha-galactosidase gene (GLA) that codes human alpha-Galactosidase A (α-Gal A). To date, over 800 GLA mutations have been found to cause Fabry disease (FD). Continued enhancement of the GLA mutation spectrum will contribute to a deeper recognition and underlying mechanisms of FD. In this study, a 27-year-old male proband exhibited a typical phenotype of Fabry disease. Subsequently, family screening for Fabry disease was conducted, and high-throughput sequencing was employed to identify the mutated gene. The three-level structure of the mutated protein was analyzed, and its subcellular localization and enzymatic activity were determined. Apoptosis was assessed in GLA mutant cell lines to confirm the functional effects. As a result, a new mutation, c.777_778del (p. Gly261Leufs*3), in the GLA gene was identified. The mutation caused a frameshift during translation and the premature appearance of a termination codon, which led to a partial deletion of the domain in C-terminal region and altered the protein's tertiary structure. In vitro experiments revealed a significant reduction of the enzymatic activity in mutant cells. The expression was noticeably decreased at the mRNA and protein levels in mutant cell lines. Additionally, the subcellular localization of α-Gal A changed from a homogeneous distribution to punctate aggregation in the cytoplasm. GLA mutant cells exhibited significantly higher levels of apoptosis compared to wild-type cells.

Incidence Trends of Inherited Anemias at the Global, Regional, and National Levels Over Three Decades.

Inherited anemia continues to pose a significant public health concern on a global scale, owing to its extensive geographical prevalence, substantial patient population, and profound ramifications. Here, we investigated detailed information on inherited anemias (including thalassemias, thalassemias trait, sickle cell disease, sickle cell trait, G6PD deficiency, and G6PD trait) for the period 1990-2019 from the Global Burden of Disease study. Over the course of three decades, there has been a persistent rise in the incidence of inherited anemias worldwide, culminating in a total of 44,896,026 incident cases in 2019. However, the prevalence of inherited anemias has exhibited a consistent downward trend over successive years. Significantly, these inherited anemias primarily impact females, exhibiting a male-to-female ratio of 1:1.88. Among males, the most prevalent inherited anemia is G6PD deficiency, whereas G6PD trait prevails among females. The incidence rates of inherited anemias and their temporal trend exhibited significant variations across different regions, with Central Sub-Saharan Africa displaying the highest incidence rates and Central Latin America experiencing the most substantial decline. The findings of this study suggest a significant correlation between the Socio-Demographic index (SDI) and incidence rates of inherited anemias, particularly in regions with lower SDI levels such as Africa and South Asia. These results contribute valuable insights for the analysis of global trends in the burden of inherited anemias.

Selective transformation and removal of As(III) by constructed Fe-N bonds: The generation of singlet oxygen from the photoexcitation of MnPc leads to abundant ZnFe-LDH interface OH radical.

In this study, MnPc intercalated Zn/Fe layered double hydroxides (MnPc/ZF-LDH) were synthesized by pillared intercalation modification with different MnPc intercalation amounts and used for the selective transformation and removal of As(III) from the arsenate-phosphate mixed solution. Fe-N bonds were constructed by the complexation of MnPc and iron ions on the Zn/Fe layered double hydroxides (ZF-LDH) interface. The DFT calculation results show that the binding energy of Fe-N bonded to arsenite (-3.75 eV) was higher than that of phosphate (-3.16 eV), resulting in MnPc/ZnFe-LDH exhibiting high As(III) selective adsorption performance and anchoring it rapidly in the arsenite -phosphate mixed solution. The maximum adsorption capacity of 1MnPc/ZF-LDH for As(III) could reach 180.7 mg·g-1 under dark conditions. MnPc also acts as a photosensitizer to provide more active species for the photocatalytic reaction. A series of experiments demonstrated that MnPc/ZF-LDH exhibits high As(III) selective photocatalytic performance. A total of 10 mg·L-1 of As(III) was completely removed in the reaction system within 50 min in a single As(III) environment. In an environment with As(III) and PO43-, it achieved 80.0 % removal efficiency of As(III) and showed a good reuse effect. The introduction of MnPc could improve the utilization of visible light by the MnPc/ZnFe-LDH. The singlet oxygen generated from photoexciting MnPc leads to abundant ZnFe-LDH interface OH. In addition, MnPc/ZnFe-LDH shows good recyclability, making it a promising multifunctional material for the purification of arsenic-polluted sewage.

A randomized trial of Trendelenburg position for acute moderate ischemic stroke.

We aim to explore the effect of head-down position (HDP), initiated within 24 hours of onset, in moderate anterior circulation stroke patients with probable large artery atherosclerosis (LAA) etiology. This investigator-initiated, multi-center trial prospective, randomized, open-label, blinded-endpoint, multi-center and phase-2 trial was conducted in China and completed in 2021. Eligible patients were randomly assigned (1:1) into the HDP group receiving -20° Trendelenburg, or control group receiving standard care according to national guideline. The primary endpoint was proportion of modified Rankin Scale (mRS) of 0 to 2 at 90 days, which is a scale for measuring the degree of disability after stroke. 90-day mRS was assessed by a certified staff member who was blinded to group assignment. A total of 96 patients were randomized (47 in HDP group and 49 in control group) and 94 (97.9%) patients were included in the final analysis: 46 in HDP group and 48 in control group. The proportion of favorable outcome was 65.2% (30/46) in the HDP group versus 50.0% (24/48) in the control group (unadjusted: OR 2.05 [95%CI 0.87-4.82], P = 0.099). No severe adverse event was attributed to HDP procedures. This work suggests that the head-down position seems safe and feasible, but does not improve favorable functional outcome in acute moderate stroke patients with LAA. This trial was registered with ClinicalTrials.gov, NCT03744533.

TG-interacting factor 1 improves risk stratification in patients with NPM1-mutated acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous disease characterized by diverse genetic abnormalities. The NPM1 is the most commonly mutated gene in newly diagnosed patients. Optimizing risk stratification in this population could facilitate more rational clinical decision-making. OBJECTIVES: To identify biomarkers that optimize risk stratification in AML patients with NPM1 mutations. MATERIAL AND METHODS: Acute myeloid leukemia patients from multiple centers were included in this study. Univariate, multivariate and Kaplan-Meier survival analyses were used to assess risk factors and clinical outcomes. The gene set enrichment analysis (GSEA) was conducted to identify the related enrichment of biological function. RESULTS: TG-interacting factor 1 (TGIF1) is a good prognostic indicator of disease progression in AML patients. It is closely related to NPM1 mutation, in which age and TGIF1 expression are independent prognostic factors. Multicenter data sources have shown that high expression of TGIF1 is beneficial for AML, regardless of whether patients received bone marrow transplantation. In the NPM1-mutated AML group, age, FLT3-ITD and TGIF1 were independent prognostic factors. Moreover, the NPM1-mutated subgroup could be well dichotomized into 2 groups with distinct prognoses through TGIF1 combined with European LeukemiaNet (ELN) 2017 risk stratification. CONCLUSIONS: The TGIF1 has an important value in the prognosis of AML. The NPM1-mutated patients were further subdivided into risk stratification groups based on TGIF1 expression, which could optimize the ELN 2017 to achieve individualized treatment.

Universal and Sensitive Drug Assessment Biosensing Platform Using Optimal Mechanical Beating Detection of Single Cardiomyocyte.

The preclinical assessment of efficacy and safety is essential for cardiovascular drug development in order to guarantee effective prevention and treatment of cardiovascular disease and avoid human health endangerment and a huge waste of resources. Rhythmic mechanical beating as one of the crucial cardiomyocyte properties has been exploited to establish a drug assessment biosensing platform. However, the conventional label-free biosensing platforms are difficult to perform high-throughput and high-resolution mechanical beating detection for a single cardiomyocyte, while label-based strategies are limited by pharmacologically adverse effects and phototoxicity. Herein, we propose a biosensing platform involving the multichannel electrode array device and the universal mechanical beating detection system. The platform can determine the optimal characteristic working frequency of different devices and dynamically interrogate the viability of multisite single cardiomyocytes to establish the optimized cell-based model for sensitive drug assessment. The subtle changes of mechanical beating signals induced by cardiovascular drugs can be detected by the platform, thereby demonstrating its high performance in pharmacological assessment. The universal and sensitive drug assessment biosensing platform is believed to be widely applied in cardiology investigating and preclinical drug screening.

Dual roles of ANGPTL4 in multiple inflammatory responses in stomatitis mice.

BACKGROUND: Stomatitis is inflammation of the oral mucosa. Angiopoietin-like protein 4 (ANGPTL4) has pleiotropic functions both anti-inflammatory and pro-inflammatory properties. In the present study, we tested whether there is a correlation between increased ANGPTL4 expression and inflammation in stomatitis mice and the mechanisms involved. METHODS AND RESULTS: In this study, the oral mucosa of mice was burned with 90% phenol and intraperitoneal injection of 5-fluorouracil to establish the model of stomatitis mice. The pathological changes of stomatitis mice were observed by H&E staining of paraffin section. The expressions of cytokines and ANGPTL4 were detected by fluorescence quantitative PCR, and the protein levels of ANGPTL4 were detected by western blot. Compared with control group, the oral mucosal structure of model mice was damaged. The expression of ANGPTL4 were significantly increased concomitantly with elevated production of anti-inflammatory cytokine (peroxisome proliferator-activated receptor alpha) and pro-inflammatory cytokines [nuclear transcription factor-kappa B, interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α] in mice with stomatitis. CONCLUSIONS: This study suggests that ANGPTL4 may be a double-edged sword in multiple inflammatory responses in stomatitis mice.

Anodic Stripping Voltammetric Analysis of Trace Arsenic(III) on a Au-Stained Au Nanoparticles/Pyridine/Carboxylated Multiwalled Carbon Nanotubes/Glassy Carbon Electrode.

A Au-stained Au nanoparticle (Aus)/pyridine (Py)/carboxylated multiwalled carbon nanotubes (C-MWCNTs)/glassy carbon electrode (GCE) was prepared for the sensitive analysis of As(III) by cast-coating of C-MWCNTs on a GCE, electroreduction of 4-cyanopyridine (cPy) to Py, adsorption of gold nanoparticles (AuNPs), and gold staining. The Py/C-MWCNTs/GCE can provide abundant active surface sites for the stable loading of AuNPs and then the AuNPs-initiated Au staining in HAuCl4 + NH2OH solution, giving a large surface area of Au on the Aus/Py/C-MWCNTs/GCE for the linear sweep anodic stripping voltammetry (LSASV) analysis of As(III). At a high potential-sweep rate of 5 V s-1, sharp two-step oxidation peaks of As(0) to As(III) and As(III) to As(V) were obtained to realize the sensitive dual-signal detection of As(III). Under optimal conditions, the ASLSV peak currents for oxidation of As(0) to As(III) and of As(III) to As(V) are linear with a concentration of As(III) from 0.01 to 8 µM with a sensitivity of 0.741 mA µM-1 and a limit of detection (LOD) of 3.3 nM (0.25 ppb) (S/N = 3), and from 0.01 to 8.0 µM with a sensitivity of 0.175 mA µM-1 and an LOD of 16.7 nM (1.20 ppb) (S/N = 3), respectively. Determination of As(III) in real water samples yielded satisfactory results.

Simultaneous oxidation of As(III) and reduction of Cr(VI) by NiS-CdS@biochar through efficient oxalate activation: The key role of enhanced generation of reactive oxygen species.

The reutilization of exhausted biochar is attracting extensive interest among researchers. In this study, the biochar generated from Chinese fir with natural regular porous structure that adsorbed Cd2+/Ni2+ at different concentration levels was used as the precursor, and then combined with simple hydrothermal vulcanization and ion deposition to generate the p-n heterojunction between NiS and CdS compounds (NiS-CdS@C) in situ. The hybrids with 3 cycles of NiS deposition reduced the interfacial transmission resistance from 80 Ω to 40 Ω, and increased photocurrent density by 5 times, thus effectively promoting the separation of photogenerated electrons and holes. The simultaneous removal of As(III) and Cr(VI) was selected to evaluate the oxidation and reduction capacity of the visible light/NiS-CdS@C/oxalate system. The results indicated that 10 mg/L As(III) and Cr(VI) were completely and simultaneously removed with 0.75 mM oxalate addition within 40 min in the system, and the NiS-CdS@C presented good durability and stability for oxalate activation. Electron paramagnetic resonance (EPR) and quenching experiments demonstrated that oxalate was activated by holes under light to produce •CO2- and enhanced the generation of additional •OH and •O2-, further contributing to the oxidation of As(III) and reduction of Cr(VI).

Comparative study on fecal flora and blood biochemical indexes in normal and diarrhea British Shorthair cats.

In recent years, 16S ribosomal DNA (16S rDNA) sequencing has been widely developed. In the present study, we investigated the changes of fecal flora analyzed by sequencing of 16S rDNA and the alteration of blood biochemical indexes in cats during diarrhea. Seven normal fecal samples and seven fecal samples of British Shorthair cats with bacterial diarrhea about 6 months old were collected. The 16S rDNA V3 region of the bacteria was amplified for high-throughput sequencing. Finally, species analysis at various levels was performed. At the same time, samples of blood were taken to examine the changes of biochemical indexes in cats with diarrhea. The abundance and diversity of microflora in the healthy group were greater than those in the diarrhea group. The normal floras in the feces of healthy cats were Firmicutes, Actinobacteria, Bacteroidetes and Proteobacteria. The content of Proteobacteria and Firmicutes varied greatly in diarrheal cats. In addition, the number of white blood cells, lymphocytes, neutrophils, and globulin were increased in cats with diarrhea, whereas albumin level was decreased in diarrheal cats. In conclusion, the present study suggests 16SrDNA technology showed that the intestinal Proteus was abundant, and the content of Firmicutes was scarce in cats with diarrhea. Escherichia-Shigella was the main pathogens in this sample. Rapid blood biochemical tests may help clinicians to assess the severity and prognosis of cats with diarrhea.

Radical-Mediated Cascade Spirocyclization of N-Benzylacrylamides with Polyhaloalkanes: Access to Polyhalo-Substituted Azaspirocyclohexadienones.

A novel and mild metal-free catalyzed radical-mediated cascade spirocyclization of N-benzylacrylamides with polyhaloalkanes is proposed for the preparation of polyhalo-substituted azaspirocyclohexadienones. Notably, polyhaloalkanes are employed as efficient alkyl radical sources via the cleavage of C(sp3)-H bonds. This protocol undergoes a cascade radical addition and intramolecular cyclization/dearomatization process, and enables the easy construction of multiple chemical bonds and a spiro ring in a single reaction.

Whole exome sequencing identifies monogenic forms of nephritis in a previously unsolved cohort of children with steroid-resistant nephrotic syndrome and hematuria.

BACKGROUND: Alport syndrome (AS), atypical hemolytic-uremic syndrome (aHUS), and fibronectin-glomerulopathy (FG) are rare forms of glomerular diseases that manifest in a combination of proteinuria, hematuria, and hypertension, referred to as nephritic syndrome. Due to phenotypic overlays, steroid-resistant nephrotic syndrome (SRNS) and nephritic syndrome have been difficult to discern diagnostically. SRNS is more common than nephritic syndrome and is the second leading cause of childhood-onset CKD. Fourteen monogenic causes of AS, aHUS, and FG and 60 monogenic causes of SRNS have been identified. As whole exome sequencing (WES) allows for unequivocal molecular genetic diagnostics, we hypothesize to be able to identify causative mutations in genes known to cause nephritic syndrome in patient cohorts with a clinical diagnosis of SRNS. METHODS: We identified patients with hematuria and steroid-resistant proteinuria in an international patient cohort that we had submitted to WES and who were unsolved for known monogenic causes of SRNS. These 70 patients from 65 individual families were subsequently analyzed for causative mutations in 14 AS, aHUS, or FG causing genes. WES data were compared to a control cohort of 76 patients from 75 families that were diagnosed with nephronophthisis-related ciliopathies (NPHP-RC) and to a control cohort of 83 individuals from 75 families with SRNS, but without hematuria. RESULTS: We detected likely pathogenic genetic variants in 3 of 65 families (4.6%) in 2 of the 14 genes analyzed. CONCLUSIONS: We confirmed that in cohorts of childhood-onset SRNS, patients with nephritic syndrome can be discerned by WES. The findings highlight the importance of clinical genetic testing for therapeutic and preventative measures in patients with proteinuria. A higher resolution version of the Graphical abstract is available as Supplementary information.

Enhanced As(III) transformation and removal with biochar/SnS2/phosphotungstic acid composites: Synergic effect of overcoming the electronic inertness of biochar and W2O3(AsO4)2 (As(V)-POMs) coprecipitation.

The activation of carbon atoms in biochar is an important approach for realizing the reuse of discarded woody biomass resources. In this work, a strategy for the construction of carbon-based catalysts was proposed with Magnoliaceae root biomass as a carbon source, doped by SnS2 and further decorated with heteropoly acid. The introduction of SnS2 can activate the carbon atom and destroy the electronic inertness of the disordered biochar with 002 planes. In addition, the synergy between the Keggin unit of phosphotungstic acid and biochar/SnS2 can suppress recombination of e--h+ carriers. The adsorption and photocatalysis experiments results showed that the efficiency of removing As(III) by biochar/SnS2/phosphotungstic acid (biochar/SnS2/PTA) systems was 1.5 times that of biochar/SnS2 systems, and the concentration of total arsenic in the biochar/SnS2/PTA composite system gradually decreased during the photocatalysis process. The formation of As-POMs can simultaneously realize As(III) photooxidation and As(V) coprecipitation. The phase transfer of arsenic by As-POMs could significantly increase the As adsorption capacity. Specifically, the composites achieved the conversion of S atoms at the interface of biochar into SO4•- radicals to enhance the As(III) photooxidation performance.

Pyridine-2-sulfonic (or carboxylic) acid modified glassy carbon electrode for anodic stripping voltammetry analysis of Cd2+ and Pb2.

Monolayer-scale pyridine-2-sulfonic acid (PySA) or pyridine-2-carboxylic acid (PyCA) modified glassy carbon electrode (GCE) was prepared for anodic stripping voltammetry (ASV) analysis of Cd2+ and Pb2+. PySA or PyCA was covalently modified on GCE by electroreduction of PySA or PyCA in 0.5 M aqueous H2SO4, yielding a PySA/GCE or PyCA/GCE. The electrodes were characterized by X-ray photoelectron spectroscopy and electrochemical techniques. In combination with the in-situ bismuth film method, both PySA/GCE and PyCA/GCE offered very high analytical performance for ASV analysis of Cd2+ and Pb2+, including the very low values of limit of detection (LOD, S/N = 3) and high stability. The PySA/GCE gave a LOD of 4 ppt for Cd2+ or of 7 ppt for Pb2+. The PyCA/GCE gave a LOD of 7 ppt for Cd2+ or of 11 ppt for Pb2+. The Cu2+ and Ni2+ interferences, which still appear as a challenge for ASV analysis of Cd2+ and Pb2+, were found to be well inhibited by the additions of K4Fe(CN)6 and Ga(III) into the detection solution. The modified electrode was used for Cd2+ and Pb2+ analysis in real water samples with satisfactory results.

Positive association of SCD1 genetic variation and metabolic syndrome in dialysis patients in China.

Aim: Metabolic syndrome (MetS) diagnosed in the dialysis patients is increasingly reported which worsens the prognosis of the renal diseases. The relationship of SCD1 with MetS is largely unknown. The purpose of this study was to investigate the relationship between SCD1 polymorphism and MetS in dialysis patients. Methods: A cross-sectional study was conducted on 323 Chinese dialysis patients, and the correlation between the seven SNPs of SCD1 gene (rs10883465, rs2060792, rs1502593, rs522951, rs3071, rs3978768 and rs1393492) and MetS was analyzed. Results: One tag-SNP (rs1393492) has significantly associated with the prevalence of MetS. Dialysis patients with rs1393492 AA genotype of SCD1 are more prone to MetS (p = 0.021). Conclusion: This study shows that the rs1393492 variations of SCD1 gene are related with the development of MetS in Chinese dialysis patients.

Procyanidin B2 from lotus seedpod regulate NO/ADMA/DDAH pathway to treat insomnia in rats.

Recent studies show that nitric oxide/asymmetric dimethylarginine/dimethylarginine dimethylaminohydrolase (NO/ADMA/DDAH) pathway may contribute to the development of sleep disorder. The objective of this study was to explore the inhibitory effect of procyanidin B2 from lotus seedpod (LSPC), a naturally occurring catechin compound, on insomnia and the mechanisms involved. The experiments were performed in brain from Sprague-Dawley rat control and insomniac rats treated or not with LSPC (15, 30, and 45 mg/kg, intragastrically) for 7 days. LSPC treatment reduced walking time and forelimb lifting-up frequency, cerebral levels of noradrenaline, glutamic acid, ADMA, sleep latency, and 8-isoprostane; increased sleep duration, cerebral concentrations of 5-hydroxytryptamine, γ-aminobutyric acid, and NO concomitantly with upregulated cerebral expression of DDAH 1, DDAH2, and neuronal NO synthases in insomniac rats. The present results suggest that LSPC may regulate NO/ADMA/DDAH pathway by inhibiting oxidative stress to treat insomnia in rats when sleep evaluation was achieved on the basis of behavioral criteria.

Improving Photovoltaic and Enzymatic Sensing Performance by Coupling a Core-Shell Au Nanorod@TiO2 Heterostructure with the Bioinspired l-DOPA Polymer.

The photoelectrochemistry (PEC) performance of TiO2 is somewhat limited by its wide band gap and low quantum efficiency, and the innovation of its composite materials provides a promising solution for an improved performance. Herein, a composite of a Au nanorod@TiO2 core-shell nanostructure (AuNR@TiO2) and a melanin-like l-DOPA polymer (PD) is designed and prepared, where the outer layer PD tethered by TiO2-hydroxyl complexation and the AuNR core can intensify the long-wavelength light harvesting, and the AuNR@TiO2 core-shell structure can strengthen the hot-electron transfer to TiO2. The photocurrent of PD/AuNR@TiO2 is 8.4-fold improved versus that of commercial TiO2, and the maximum incident photon-to-electron conversion efficiency reaches 65% in the UV-visible-near-infrared region. In addition, the novel PD/AuNR@TiO2 photocatalyst possesses the advantages of good biocompatibility and stability, which can act as a versatile PEC biosensing platform for providing a biocompatible environment and improving detection sensitivity. Herein, a PEC enzymatic biosensor of glucose is developed on the basis of the immobilization of dual enzyme [glucose oxidase (GOx) and horseradish peroxidase (HRP)] in PD and the signaling strategy of biocatalytic precipitation. In phosphate buffer containing glucose and 4-chloro-1-naphthol, the HRP-catalyzed oxidation of 4-chloro-1-naphthol by GOx-generated H2O2 can form a precipitate on the electrode, by which the decrement of photocurrent intensity is proportional to the common logarithm of glucose concentration. The linear detection range is from 0.05 µM to 10.0 mM glucose, with a limit of detection of 0.01 µM (S/N = 3). Glucose in some human serum samples is analyzed with satisfactory results.

Down-regulation of serum miR-151a-3p is associated with renal tissue activity in class IV lupus nephritis.

OBJECTIVES: The aim of this study was to explore the value of serum miRNA for evaluating renal tissue activity in patients with class IV lupus nephritis (LN). METHODS: First, we used a microRNA array to identify miRNAs differentially expressed between class IV LN patients and healthy volunteers (n=4/group). Then, we analysed the association between these identified miRNAs and renal tissue activity in class IV LN patients. Finally, to validate the results, 20 class IV LN patients (confirmed by renal biopsy) and 20 healthy control volunteers were further studied. RESULTS: We found 23 miRNAs to be significantly differentially expressed between the 2 groups. We selected 5 of these miRNAs (miR-3165, miR-4762-5p, miR-146a-5p, miR-151a-3p, and miR-21-5p) for further experiments. In validation experiments, expression of miRNA-151a-3p was significantly down-regulated in the class IV LN group compared to that in the control group (p<0.01) and was negatively correlated with the activity index (AI) in the class IV LN group(r=-0.526, p=0.017); the internal correlation was described with a linear fitting equation (p<0.01). CONCLUSIONS: Serum miR-151a-3p expression was decreased in class IV LN patients compared with healthy control volunteers and was negatively correlated with renal tissue activity. Thus, miR-151a-3p may play a employed for diagnosing class IV LN and evaluating renal tissue activity.

Paeoniflorin regulates GALNT2-ANGPTL3-LPL pathway to attenuate dyslipidemia in mice.

N-acetylgalactosaminyltransferase 2-Angiopoietin-like protein 3-lipoprotein lipase (GALNT2-ANGPTL3-LPL) pathway may be a useful pharmacologic objective for dyslipidemia. The present study was conducted to test the effect of paeoniflorin, a monoterpene Glycoside, on dyslipidemia in mice. Fifty mice were randomly divided into five groups (n = 10): three groups of apolipoprotein E-null (ApoE-/-) mice treated with paeoniflorin (10 or 20 or 30 mg/kg/day), untreated ApoE-/- mice group, and C57BL/6J control group. Six weeks after treatment, expression of hepatic ANGPTL3, hepatic GALNT2 and adipose tissue LPL, lipid levels in the liver and blood were quantified. Treatment with paeoniflorin (10 or 20 or 30 mg/kg) obviously down-regulated expression of ANGPTL3 and up-regulated expressions of GALNT2 and LPL concomitantly with elevated plasma high-density lipoprotein cholesterol level, reduced plasma concentrations of low-density lipoprotein cholesterol, total cholesterol, triglyceride, malonaldehyde, and 8-isoprostane. The present results suggest that paeoniflorin regulates GALNT2-ANGPTL3-LPL pathway to attenuate dyslipidemia in mice.