Biology subjects

Xu, G.

Publications and source records attributed to Xu, G..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Coordinate Up-regulation of Both TK1 and TS Expression in Cycling Cells: Mechanistic Basis and Implications for Dual-Targeted Cancer Therapy

Our previous study [2] has revealed that various types of cycling cells undergo rapid proliferation and division. Cycling cells can be broadly categorized into two groups: cycling immune cells (CICs) and cycling non-immune cells (CNICs). Cancer cells represent a special type of cycling cells. Based on a set of 26 marker genes, we proposed a simple method for the rapid identification of cycling-cell types. Comparisons across cycling-cell types uncovered novel gene-regulatory mechanisms underlying the cell cycle, development, and differentiation. Notably, we discovered that the coordinate up-regulation of both TS and TK1 expression is indispensable for securing a robust deoxythymidine triphosphate (dTTP) supply required for DNA replication in cycling cells. The compensatory interplay between salvage and de novo synthesis provides a plausible explanation for resistance to 5-fluorouracil (5-FU), a TS inhibitor for cancer chemotherapy. Consequently, blocking dTTP synthesis requires co-inhibition of TK1 and TS. For the first time, we present the crucial single-cell transcriptome evidence for this coordinate up-regulation, thereby establishing the mechanistic basis for developing TK1/TS as a dual target in cancer therapy.

cancer biology↗

bioRxiv2025

A minor muscle stem cell population functions as metabolic Trojan horse fueling systemic aging by succinate induced epigenetic reprogramming

Inflammaging, the sustained chronic inflammation, is a hallmark of aging, yet its sustained activation mechanism remains elusive. Here, we identified muscle stem cells (MuSCs) as a driver of systemic inflammaging, evidenced by the multi-organ inflammation and aging phenotypes in MuSC specific Tet2 knockout mice. Tet2-Hdac11-Acod1-SDH axis maintained normal succinate level in MuSCs. Tet2 knockout disrupted this enzymatic cascade and led to succinate accumulation, fueling H4K31succ elevation to directly activate inflammatory gene transcription in MuSCs. The excess succinate was delivered to muscle fibers by sporadic fusion of Tet2 knockout MuSCs during muscle homeostasis, activated pro-inflammatory program, and transformed muscle to a persistent pro-inflammatory factor secretory organ, sustaining systemic inflammaging. Moreover, Tet2 was downregulated in aged MuSCs suggesting that this coupled metabolic-epigenetic mechanism was active in physiological aging. These findings reveal that a small subset of dysregulated MuSCs activate sustained whole-body inflammaging and multi-organ aging, providing new targets for rejuvenation strategy development.

cell biology↗

bioRxiv2025

Structural and biochemical studies of human PP2A(B55) holoenzyme and ENSA protein complex

The serine/threonine protein phosphatase 2A (B55) holoenzyme (PP2A(B55)), a key cell cycle regulator, is tightly regulated by ENSA, whose phosphorylation at Ser67 inhibits PP2A(B55). The structural basis for how pENSA orchestrates this inhibition to govern mitotic progression remains unclear. In this study, we disapproved the previous hypothesis of direct ENSA-PP2A A subunit interaction, and showed that the ENSA-PP2A(B55) interaction requires the PP2A holoenzyme. We then determined cryo-EM structure of the PP2A(B55)-ENSAS67D complex at 3.03 [A] resolution, which reveals four distinct regions of ENSA, each engaging specific sites on the B55 or C subunits. The structure reveals an extended, inhibited conformation of the PP2A(B55) holoenzyme, which contrasts sharply with the contracted, active state of apo PP2A(B55). pENSA binding induces the C subunit to shift away from the B55 subunit, with the pS67-containing motif inserting into the catalytic site of C subunit and locking the PP2A(B55) holoenzyme in an inactive state. Our work also revealed novel ligand-binding surfaces on B55, and expanded definition of the short linear motif (SliM). Overall, our work provided novel insights into PP2A regulation during cell cycle, and offers new avenues for the discovery of specific PP2A(B55) inhibitors and modulators.

biophysics↗

bioRxiv2025

Age-varying DNA methylation patterns associated with blood pressure across the lifespan

BackgroundEpigenome-wide association studies (EWAS) have identified associations between DNA methylation and blood pressure, yet most rely on single-time-point data and cannot capture how methylation and blood pressure relationships change with age. MethodsWe conducted a longitudinal EWAS of 1,945 blood samples from 976 participants in the Multi-Ethnic Study of Atherosclerosis using a spline-based varying-coefficient model to detect age-dependent associations between DNA methylation in blood and blood pressure traits. Findings were evaluated for replication in 1,187 samples from the Framingham Heart Study. Models were adjusted for sex, ancestry, and leukocyte composition to account for cellular heterogeneity. ResultsSix CpG sites showed significant age-dependent associations with systolic or pulse pressure after correction for multiple testing. These included loci within STIP1, CSRP1, and KDM6A that replicated in the Framingham cohort. Several CpG sites demonstrated a reversal of effect direction with advancing age, where higher methylation was associated with higher systolic pressure in younger adults but lower pressure later in life. Pathway enrichment analyses identified focal adhesion, actin cytoskeleton remodeling, and Wnt/{beta}-catenin signaling, which are processes relevant to vascular aging. Drug target mapping identified 23 FDA-approved agents interacting with genes at these loci. ConclusionsBlood-derived DNA methylation shows dynamic age-related associations with blood pressure that likely reflect systemic or vascular aging processes rather than direct cellular mediation. Longitudinal analytical frameworks can reveal temporal patterns in epigenetic variation that are not detectable in single time point studies and may inform the discovery of biomarkers for age related cardiovascular risk.

genetics↗

bioRxiv2025

The Notch/snRNA negative feedback regulation and its implications in Alzheimer's disease

Alzheimers disease (AD) is a multifactorial disorder whose hallmark lesions have been recognized for more than a century, yet its molecular pathobiology remains fragmentary. During our AD research, we discovered a direct mechanistic axis that links the Notch signalling pathway -- a crucial regulator of cell differentiation and proliferation--with the small nuclear RNAs (snRNAs) that drive pre-mRNA splicing. For the first time, our discovery unifies two previously siloed paradigms -- cell signal transduction and RNA splicing, expanding the fundamental knowledge of gene expression and its regulation. The first contribution of the present study is the discovery and validation of the Notch/snRNA negative feedback regulation. More implications include: (1) it reframes splicing-related diseases as dynamic consequences of pathway dysregulation rather than static snRNA-gene mutations; (2) it explains why global splicing abnormalities appear in AD, aging, and cancer even when snRNA genes themselves are not mutated; and (3) it provides an immediate, druggable "splicing rheostat" for any Notch-hyperactive disorder, such as AD.

cell biology↗

bioRxiv2025

Domestication and Improvement Reshaped the Genomic Architecture of Abiotic Stress Tolerance in Sunflower

Sunflower (Helianthus annuus) has undergone extensive domestication and modern improvement, yet the extent to which selection has shaped its stress-adaptive variation remains largely unclear. Using genomic data from diverse accessions, including the wild ancestor of sunflower, we identified widespread balancing selection that maintains historical polymorphisms in abiotic-stress-related genes. Additionally, we identified strong positive selection signals associated with domestication and improvement. Using a cutting-edge DNA language model to characterize deleterious alleles, we found that modern cultivars exhibited an elevated deleterious mutation load, particularly within positively selected regions, consistent with patterns observed in other major domesticates. To cross-validate the functional consequences of the selected regions on stress responses, we assessed salt tolerance in an independent association panel and evaluated ancestral allele effects on salt-responsive traits. Although only a small subset of the selected regions reached genome-wide significance, several ancestral alleles within positively selected sweeps tended to enhance salt tolerance. Together, these results indicate that recent selection may have unintentionally eliminated historically beneficial alleles, reshaping the genomic landscape of sunflower stress responses. This study highlights a breeding strategy to recover ancestral beneficial alleles for enhancing abiotic stress tolerance in modern cultivars.

genomics↗

bioRxiv2025

The dominance of gene expression controlled by trans-eQTL hotspots contributes to phenotypic heterosis in maize

Heterosis, or hybrid vigor, is a key phenomenon in genetics research and agricultural production, and has been primarily attributed to non-additive genetic effects such as dominance -- a prevailing consensus shaped by decades of empirical research and theoretical debate. Although dominance may arguably arise from distal modifiers, their selective advantage is debated due to presumably small individual effects. To address this long-standing question, particularly how genetic dominance manifests at the transcriptomic level and contributes to phenotypic heterosis, we integrated transcriptomic and phenotypic data from a large population of maize hybrids and their inbred parents. We found that [~] 30% of the expressed seedling genes in a significant proportion of hybrids exhibited expression patterns deviating from the average of the two parents, indicative of non-additivity. Further analysis suggests that while hybrid gene expression per se is primarily regulated by cis-eQTLs, expression dominance (or non-additivity) is disproportionately controlled by trans-eQTLs. These trans-eQTLs cluster into hotspots that regulate the non-additivity of hundreds of target genes, mostly within co-expression networks, and are notably enriched for transcription factors (TFs). Focusing on one such hotspot, we functionally validated a classical maize gene ZmR1, a basic helix-loop-helix (bHLH) TF associated with multiple seedling trait heterosis, as a candidate regulator of expression dominance across hundreds of genes. Overexpression of ZmR1 enhances expression dominance of downstream genes and increases phenotypic heterosis in both seedling and adult traits. Further experiments confirmed its direct regulatory role in modulating genes involved in anthocyanin biosynthesis and lignin metabolism, driving transcriptome-level dominance. These results provide empirical support for the modifier hypothesis under an omnigenic model, suggesting that heterosis arises not from the modification of a single genes inheritance but through the coordinated regulation of hundreds of phenotype-associated genes, thereby helping to reconcile the long-standing debate over the genetic basis of dominance in heterosis.

genetics↗

bioRxiv2025

Captamer: A Novel Quantitative Protein Detecting Method Depending on Aptamer-activated Molecular Switches and RPA Signal Amplification

There are various protein assays for specific and quantitative detection and widely used for laboratory and clinic purposes, but current methods still have limitations. Immunoassays based on antibodies, like ELISA, suffer from slow response and a long antibody-screening period, while physical or electrochemical methods are generally restricted by high cost or the stringent requirement of equipment or operating skills. In this study, we developed an in vitro sensitive protein quantification method: Captamer. The Captamer system comprises a molecular switch derived from aptamer sequence and an exponential fluorescence signal amplification pathway based on recombinase polymerase amplification (RPA). We demonstrated the Captamer for SARS-CoV-2 nucleocapsid protein detection and obtained results from samples within 30 min, displaying a wide detection window from 0.2 pg/mL to 200 pg/mL with high specificity. Furthermore, we tested the Captamer for Tau441 protein (a potential Alzheimers disease biomarker) and thrombin (a classic aptamer-protein interaction model), showing the limit of detection as low as 1 ng/mL and 0.02pg/mL respectively, which suggested the capacity of Captamer to be applied to various aptamer-protein pairs. Compared with the most commonly used and recently reported protein quantification methods, Captamer stands out for its high sensitivity, short response time, low cost, and simplicity, indicating its great potential to be widely used in protein quantification. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/686180v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1e38ffaorg.highwire.dtl.DTLVardef@1019e72org.highwire.dtl.DTLVardef@1498b68org.highwire.dtl.DTLVardef@15f5ea2_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2025

An ultra-long acting insulin enables glucose-synchronised release

Delayed and weak glucose-responsive kinetics, coupled with short plasma exposure and complicated formulation, remain major obstacles to the clinical translation of glucose-responsive insulin formulations. Here we report a rapidly absorbable, ultra-long acting, and glucose-responsive insulin analogue via engineering recombinant human insulin with two phenylboronic acids. The insulin analogue has a long circulating half-life (t1/2{beta} [~]150 h) due to its unique, unprecedented, glucose-responsive binding to blood circulation-associated proteins. This interaction drives the formation of a unique systemic reservoir that allows synchronised dynamic response in insulin levels to glucose fluctuations. In type 1 diabetic mice and minipigs, a single subcutaneous dose can maintain normoglycaemia for over one week (47.5-fold compared to insulin glargine). After the last injection of four consecutive weekly administrations in mice, the glucose-lowering effect can last 800 hours. Administering this glucose-responsive insulin analogue with a fully automated insulin delivery system can leverage dual closed loops and achieve a glucose time in range of over 85% and a coefficient of variation of approximately 30%, better than the recommended targets for human therapy. Importantly, no toxicity was identified in the study.

bioengineering↗

bioRxiv2025

Analysis of Nutritional Components in Brown Sugar and Its Effects on Anti-fatigue, Alleviation of Qi Deficiency and Blood Stasis, and Antioxidant Effects

Brown sugar (BS), Red granulated sugar (RGS) and White sugar(WS) are three key sweeteners and food additives in China. Notably, BS possesses significant nutritional value and has been widely used in Chinese medicine for its supportive therapeutic properties.This study evaluated the anti-fatigue, the amelioration of qi deficiency and blood stasis, as well as the antioxidant activities of these sugars using a zebrafish model. BS and RGS demonstrated significantly greater efficacy than WS in terms of both anti-fatigue effects and amelioration of qi Deficiency and blood stasis in the zebrafish model. Antioxidant assays revealed that BS, RGS, and WS (500 g/mL) significantly enhanced superoxide dismutase (SOD) activity in zebrafish embryos compared with the control group. Furthermore, the mineral composition of sugar were determined. Nine mineral elements--potassium (K), calcium (Ca), sodium (Na), magnesium (Mg), iron (Fe), zinc (Zn), copper (Cu), phosphorus (P), and selenium (Se)--were analyzed. BS exhibited markedly higher concentrations of P, Ca, Fe, and Mg than RGS and WS, while selenium (detected at 50 mg/kg) was exclusively detected in BS. Intriguingly, RGS contained four-fold higher potassium levels than BS. Total polyphenol content, quantified by Folin-Ciocalteu assay, was 4.35 g/kg in BS and 1.53 g/kg in RGS, with no detectable polyphenols in WS.

biochemistry↗

bioRxiv2025

Hypobaric hypoxia drives citrate cycle reprogramming to suppress tumor progression

High altitude residents present lower tumor incidence and mortality than plain residents, suggesting that hypobaric hypoxia displays protective effect against tumor development. The results of our studies showed that hypobaric hypoxia exposure significantly suppressed tumor progression in subcutaneous bearing and lung metastasis tumor models. With single-cell transcriptome analysis, we identified HIF-1 pathway was significantly downregulated in tumor tissues with high altitude hypoxia, leading to decreased glycolysis and angiogenesis and improved antitumor immune response. Mechanistically, systemic hypoxia rewired citric acid cycle, with enhanced CS and IDH2 expression and reduced OGDH and SUCLG2 expression, to induce -ketoglutarate accumulation and succinate decline in tumor microenvironment, further mediating HIF-1 pathway inhibition. Moreover, hypobaric hypoxia treatment significantly improved the antitumor effects of adjuvant therapies (including chemotherapy, anti-angiogenic therapy and immunotherapy). Our findings reveal the role and mechanism of hypobaric hypoxia for tumor regression and yield new insights into tumor therapy.

cancer biology↗

bioRxiv2025

Scavenger Receptor class F member 2 is an intracellular receptor for Hepatitis B virus

Hepatitis B virus (HBV) infects hepatocytes by specific binding to the cell-surface receptor --sodium taurocholate cotransporting polypeptide (NTCP)--through the preS1 region of its large envelop protein, followed by a less well understood transport process across the cytoplasm to the nucleus. Here, we report that scavenger receptor class F member 2 (SCARF2), a single-pass transmembrane protein, functions as an intracellular receptor for HBV. SCARF2 binds to a preS1 region downstream of the NTCP binding site through its N-terminal EGF-like domains 4-6, and its proline-rich C-terminal domain also plays an indispensable role in the infection. The internalized HBV virions are transported to the cytoplasmic side of nuclear pore complexes (NPCs) within the SCARF2-containing endosomes. HBV capsid release from the endosomal vesicles is significantly impaired by knockdown of SCARF2. These results suggest a model that SCARF2 conveys HBV to the periphery of NPCs and ultimately leads to viral capsid release for nuclear entry.

microbiology↗

bioRxiv2025

Separable Spatial Single-cell Transcriptome Representation Learning via Graph Transformer and Hyperspherical Prototype Clustering

Spatial transcriptomics enables the exploration of cell types, spatial domain organization, and cell-cell communication at tissue scale, serving as a powerful link between tissue morphology and molecular function. However, existing methods still struggle with limited spatial resolution, poor robustness in multi-slice alignment, and suboptimal ligand-receptor (L-R) detection in complex tissues. To address these challenges, we propose S3RL (Separable Spatial Single-cell transcriptome Representation Learning via Graph Transformer and Hyperspherical Prototype Clustering), a unified framework that integrates gene expression, spatial coordinates, and histological image features via a graph neural network and hyperspherical prototype-based separable representation learning. In spatial clustering tasks, S3RL improves the average Adjusted Rand Index (ARI) by nearly 120% on the Nanostring lung cancer dataset and over 26% on the 10X DLPFC dataset compared to state-of-the-art methods. For multi-slice spatial alignment, S3RL achieves an average ARI improvement of over 65.4% in partial brain slices and over 48.3% in complete slices relative to GraphST, highlighting its superior robustness and alignment consistency across heterogeneous spatial inputs. Moreover, S3RL reveals more biologically meaningful ligand-receptor signaling relationships, enhancing the interpretability of cell-cell communication patterns. Together, these results demonstrate S3RLs effectiveness in enhancing spatial resolution, cell type identification, and biological insight across diverse spatial transcriptomics datasets.

bioinformatics↗

bioRxiv2025

GenVS TBDB: An Open AI-Generated andVirtual Screened Small-Molecule Database for Tuberculosis Drug Discovery

Tuberculosis (TB) remains a leading global health threat, with over 10 million new cases and 1.25 million deaths reported in 2023. Current TB therapies rely on a limited drug repertoire and prolonged treatment courses that have changed little in four decades. Here, we present GenVS-TBDB, a target-aware AI-generated and virtual-screened small-molecule database, which expands the chemical space against Mycobacterium tuberculosis (M.tb) essential proteins. We first identified 460 probable small-molecule binding pockets across 377 essential M.tb proteins by integrating multiple sources. Then, by leveraging the target-aware molecule generative model, over 1.2 million novel small molecules tailored to these pockets were produced. The key physicochemical properties were computed for all compounds to ensure medicinal chemistry tractability. These compounds were also evaluated using molecular docking and anti-TB specific graph neural network model, yielding binding propensity ranking and whole-cell activity prioritization for each target. To substantiate the integrated AI-driven workflow for anti-TB discovery, 30 compounds were obtained, including 22 AI-designed molecules synthesized de novo and 8 commercially available analogs. In validation, 2 synthesized compounds demonstrated significant thermal stabilization of FtsZ, confirming target engagement. 6 compounds exhibited cellular inhibition below 50 {micro}M, the most potent at 12 {micro}M. Furthermore, GDI-11785 showed binding to the cell wall biosynthesis pathway with 35 {micro}M cellular activity, establishing a promising starting point for tuberculosis drug discovery. Our findings contribute a significant library of bioactive molecules which may hasten the preliminary phase of tuberculosis drug discovery. The GenVS-TBDB small library is publicly accessible and can be downloaded freely at https://datascience.ghddi.org/database/view.

pharmacology and toxicology↗

bioRxiv2025

High-resolution NMR spectroscopy of proteins in intact mitochondria

Understanding protein structure and function within mitochondria is essential for unraveling the molecular mechanisms underlying cellular energy production, stress response, and disease. Here, we present a novel approach for NMR observation of proteins within intact mitochondria by delivering proteins directly into isolated mitochondria via electroporation. Using this method, we investigate the interaction of -synuclein (-syn) with the mitochondria membrane and examine how post-translational modifications regulate this interaction. Additionally, we assessed the stability of GB1 and the dimerization of its variant within mitochondria, achieving quantitative insights into mitochondrial environmental impact on protein function. This approach offers a valuable framework for exploring mitochondrial related biomolecular events at atomic-resolution within intact mitochondria, paving the way for a more comprehensive understanding of the molecular events governing mitochondrial health and dysfunction.

biochemistry↗

bioRxiv2025

A single amino acid variant in the variable region I of AAV capsid confers liver detargeting

AAV capsid serotypes isolated from nature have been widely used in gene delivery and gene therapy. Recently, more than 1,000 distinct AAV capsids were identified from human clinical samples by high-throughput, long-read DNA sequencing. In this study, we tap into this broad natural biodiversity of AAV capsids to develop liver-tropic AAV capsids. We initially screened a subset of variants derived from AAV8 (n=159) for packaging efficiency. The high-yielding variants were subjected to a barcoded vector library screen in mice and ferrets for their ability to mediate liver gene transfer. Although no variant surpassed AAV8 for liver targeting, several exhibited a liver detargeting phenotype. Among these, we focused on the N271D variant (AAV8 VP1 numbering), located in the variable region I (VR-1), which has been previously implicated in influencing liver tropism. The liver detargeting phenotype of AAV8.N271D was confirmed by single vector administration in mice. Additionally, we grafted the N271D variant onto AAV9 and MyoAAV capsids (N270D by AAV9 VP1 numbering). The AAV9.N270D and MyoAAV.N270D vectors showed a similar liver-detargeting phenotype, although muscle targeting was moderately reduced. Although we did not identify any capsid variants that outperform AAV8 in liver transduction, this study reinforces the important role of VR-1 in modulating liver tropism and highlights the potential of engineering VR-1 residues to reduce liver gene transfer and associated toxicity observed in several gene therapy studies.

molecular biology↗

bioRxiv2025

Transcription factors instruct DNA methylation patterns in plant reproductive tissues

DNA methylation is maintained by forming self-reinforcing connections with other repressive chromatin modifications, resulting in stably silenced genes and transposons. However, these mechanisms fail to explain how new methylation patterns are generated. In Arabidopsis, CLASSY3 (CLSY3) targets the RNA-directed DNA methylation (RdDM) machinery to different loci in reproductive tissues, generating distinct epigenomes via unknown mechanism(s). Here, we discovered that several different REPRODUCTIVE MERISTEM (REM) transcription factors are required for methylation at CLSY3 targets specific to male or female reproductive tissues. We designate these factors as REM INSTRUCT METHYLATION (RIMs) and demonstrate that disruption of their DNA binding domains, or the motifs they recognize, blocks RdDM. These findings not only reveal RIMs as the first sex-specific RdDM proteins but also establish a critical role for genetic information in targeting DNA methylation. This novel mode of targeting expands our understanding of how methylation is regulated to include inputs from both genetic and epigenetic information.

plant biology↗

bioRxiv2025

ND-13, a DJ-1 derived peptide, as a novel pharmacological approach in the prevention of NLRP3 inflammasome activity in Diabetic Nephropathy

Diabetic nephropathy is the most important cause of renal failure worldwide and is characterized by sustained inflammation regulated in part by NLRP3 Inflammasome. Attenuation of inflammation is a major priority to prevent renal damage. Our previous publications show that DJ-1 has antioxidant and anti-inflammatory properties in the kidney. ND-13 is a short peptide consisting of 13 amino acids of the DJ-1-protein, which could increase DJ-1 pathway activation. The aim of these studies was to determine the role of NLRP3 in the pathogenesis of diabetic nephropathy and to study the possible renal protective effects of the DJ-1 pathway in diabetic mice and on inflammasome regulation. Bone marrow derived macrophages were treated with ND-13 and cultivated in high and low glucose. Diabetes was induced in C57Bl/6 mice via injection of streptozotocin and treated with ND-13 and MCC950, an inhibitor of the NLRP3 inflammasome. Peripheral mononuclear cells were isolated from human with diabetes, diabetic nephropathy and healthy donors and were plated, pretreated with ND-13 and stimulated with LPS+ATP. IL-1{beta} concentration in the medium of bone marrow derived macrophages increased by NLRP3 inflammasome stimulation by LPS+ATP, and decreased in macrophages pre-treated with ND-13, however, in the presence of LPS+Nigericin no effect was found. Peritoneal macrophages from diabetic mice were obtained and plated. Streptozotocin-induced diabetic C57BL/6 mice have increased the peritoneal cells IL-1{beta} production compared with control mice, suggesting that inflammasome may be activated in macrophages during diabetes and that ND-13 treatment normalized its activity. ND-13 and MCC950 decreased histologic evidence of tubular injury in STZ-induced diabetes in mice, additionally, significantly increased the mRNA expression of Col-I, Col-II, Tgf-{beta}, Il-6, Tnf- and P2x7 in the renal cortex, which was partially prevented by ND-13 and MCC950 pre-treatment. P2x7 mRNA expression was also increased in peritoneal macrophages obtained from diabetic mice, and its expression was attenuated by ND-13 pre-treatment. Peripheral mononuclear cells isolated from patients blood were plated and stimulated with LPS+ATP. Patients with diabetic nephropathy presented a significant increase of IL-1{beta} release compared to diabetic individuals and ND-13 could has a role in the prevention of inflammasome activation in healthy patients. Our results demonstrate that activation of the DJ-1 pathway is a promising approach to prevent renal inflammation and fibrosis during diabetes, by ameliorating inflammasome activation in peripheral immune cells. Thus, ND-13 could be a promising new therapeutic approach to attenuating inflammation and renal damage in diabetic nephropathy.

cell biology↗