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Yan, L.

Publications and source records attributed to Yan, L..

At least 73 records · Page 4Linked to original sources

Nphos: Database and Predictor of Protein N-phosphorylation

Protein N-phosphorylation widely present in nature and participates in various biological functions. However, current knowledge on N-phosphorylation is extremely limited compared to that on O-phosphorylation. In this study, we collected 11,710 experimentally verified N-phosphosites of 7344 proteins from 39 species and subsequently constructed the database Nphos to share up-to-date information on protein N-phosphorylation. Upon these substantial data, we characterized the sequential and structural features of protein N-phosphorylation. Moreover, after comparing of hundreds of learning models, we chose and optimized gradient boosting decision tree (GBDT) models to predict three types of human N-phosphorylation, achieving mean areas under the receiver operating characteristic curve (AUC) of 90.56%, 91.24%, and 92.01% for pHis, pLys, and pArg, respectively. Meanwhile, we discovered 488,825 distinct N-phosphosites in the human proteome. The models were also deployed in Nphos for interactive N-phosphosite prediction. In summary, this work provides new insights and points for both flexible and focused investigations of N-phosphorylation. It will also facilitate a deeper and more systematic understanding of protein N-phosphorylation modification by providing a data and technical foundation. Nphos is freely available at http://www.bio-add.org and http://ppodd.org.cn/Nphos/.

bioinformatics↗

GametesOmics: A Comprehensive Multi-Omics Database for Exploring the Gametogenesis in Humans and Mice

Gametogenesis plays an important role in the reproduction and evolution of species. The transcriptomic and epigenetic alterations in this process can influence the reproductive capacity, fertilization, and embryonic development. The rapidly increasing single-cell studies have provided valuable multi-omics resources. However, data from different layers and sequencing platforms have not been uniformed and integrated, which greatly limits their use for exploring the molecular mechanisms that underlie oogenesis and spermatogenesis. Here, we developed GametesOmics, a comprehensive database that integrated the data of gene expression, DNA methylation, and chromatin accessibility during oogenesis and spermatogenesis in humans and mice. GametesOmics provides a user-friendly website and various tools, including Search and Advanced Search for querying the expression and epigenetic modification of each gene; Analysis Tools with Differentially Expressed Gene (DEG) analysis for identifying DEGs, Correlation analysis for demonstrating the genetic and epigenetic changes, Visualization for displaying single-cell cluster and screening marker genes as well as master transcription factors (TFs), and MethylView for studying the genomic distribution of epigenetic modifications. GametesOmics also provides Genome Browser and Orthologs for tracking and comparing gene expression, DNA methylations, as well as chromatin accessibilities between humans and mice. GametesOmics offers a comprehensive resource for biologists and clinicians to decipher the cell fate transition in germ cell development, and can be accessed at http://gametesomics.cn/.

bioinformatics↗

CRISPR-based Genome Editing of a Diurnal Rodent, Nile Grass Rat (Arvicanthis niloticus)

Diurnal and nocturnal mammals have evolved distinct pathways to optimize survival for their chronotype-specific lifestyles. Conventional rodent models, being nocturnal, may not sufficiently recapitulate the biology of diurnal humans in health and disease. Although diurnal rodents are potentially advantageous for translational research, until recently, they have not been genetically tractable. Here, we address this major limitation by demonstrating the first successful CRISPR genome editing of the Nile grass rat (Arvicanthis niloticus), a valuable diurnal rodent. We establish methods for superovulation; embryo development, manipulation, and culture; and pregnancy maintenance to guide future genome editing of this and other diurnal rodent species.

genomics↗

Molecular blueprints of the Langya virus attachment and fusion glycoproteins

Langya virus (LayV) is a recently discovered henipavirus (HNV), isolated from febrile patients in China. HNV entry into host cells is mediated by the attachment (G) and fusion (F) glycoproteins which are the main targets of neutralizing antibodies. We show here that the LayV F and G glycoproteins promote membrane fusion with human, mouse and hamster target cells using a different, yet unknown, receptor than NiV and HeV and that NiV-and HeV-elicited monoclonal and polyclonal antibodies do not cross-react with LayV F and G. We determined cryo-electron microscopy structures of LayV F, in the prefusion and postfusion states, and of LayV G, revealing previously unknown conformational landscapes and their distinct antigenicity relative to NiV and HeV. We computationally designed stabilized LayV G constructs and demonstrate the generalizability of an HNV F prefusion-stabilization strategy. Our data will support the development of vaccines and therapeutics against LayV and closely related HNVs.

biochemistry↗

The longitudinal single-cell panorama of cynomolgus monkey ovary throughout lifespan revealed a conserved ovarian clock between primates

Ovarian function is critical for female fertility and impacts reproductive longevity. It is of great importance to accurately predict the aging process within the ovary for fertility assessment and disease diagnosis. However, cell metrics for evaluating the ovarian aging rate are still in urgent need, and molecular insights into ovarian development and dysfunction during the primate life course are also limited. Here, we reported large-scale ovarian cell atlas of consecutive development of cynomolgus monkeys across 22 years with 20 time points, covering the foetal, newborn, prepubertal, pubertal, adult, perimenopausal and menopausal stages. We characterized and validated distinct molecular signatures of each cluster of cells within primate ovaries, and uncovered a previously undocumented RHOXF1-positive oocyte type during primordial follicle assembly in primates. Furthermore, the constitution and developmental trajectories of primate germ cells, granulosa cells and stromal / theca cells were also elucidated, and their precursors were identified. More importantly, dynamics of cellular compositions were unravelled through the ovarian development, featured by granulosa, epithelial, stromal, and immune cells that showed strong temporal heterogeneity spanning lifetime, whilst referred to the key function during the corresponding stages. Based on the correlations of each cell type with age and stage-specific molecular dynamics, we further constructed a transcriptomic ovarian clock which could perceive an effective biological age prediction of the ovary and further applied to humans. The findings reveal granulosa, epithelial, and stromal cells as the highest performance predictors of ovarian biological age, while highlighting the crucial role of AGE-RAGE and Relaxin signaling pathways in regulating ovarian aging. Our work not only provide valuable resource for obtaining insights into the development, aging and dysfunction of key organs, but also establish a transcriptomic clock to predict biological ovarian aging thus to be potential clinical implementation in future.

developmental biology↗

Dendritic, delayed, and stochastic CaMKII activation underlies behavioral time scale plasticity in CA1 synapses

Behavioral time scale plasticity (BTSP), is a form of non-Hebbian plasticity induced by integrating pre- and postsynaptic components separated by behavioral time scale (seconds). BTSP in the hippocampal CA1 neurons underlies place cell formation. However, the molecular mechanisms underlying this behavioral time scale (eligibility trace) and synapse specificity are unknown. CaMKII can be activated in a synapse-specific manner and remain active for a few seconds, making it a compelling candidate for the eligibility trace during BTSP. Here, we show that BTSP can be induced in a single dendritic spine using 2-photon glutamate uncaging paired with postsynaptic current injection temporally separated by behavioral time scale. Using an improved CaMKII sensor, we saw no detectable CaMKII activation during this BTSP induction. Instead, we observed a dendritic, delayed, and stochastic CaMKII activation (DDSC) associated with Ca2+ influx and plateau 20-40 s after BTSP induction. DDSC requires both pre-and postsynaptic activity, suggesting that CaMKII can integrate these two signals. Also, optogenetically blocking CaMKII 30 s after the BTSP protocol inhibited synaptic potentiation, indicating that DDSC is an essential mechanism of BTSP. IP3-dependent intracellular Ca2+ release facilitates both DDSC and BTSP. Thus, our study suggests that the non-synapse specific CaMKII activation provides an instructive signal with an extensive time window over tens of seconds during BTSP.

neuroscience↗

SRSF1-mediated alternative splicing of Tial1/Tiar is essential for homing and self-renewal in mouse spermatogonial stem cells

AbstractSpermatogonial stem cells (SSCs) are essential for continuous spermatogenesis and male fertility. The underlying mechanisms of alternative splicing (AS) in mouse SSCs are still largely unclear. We demonstrated that SRSF1 is essential for gene expression and splicing in mouse SSCs. Crosslinking immunoprecipitation and sequencing (CLIP-seq) data revealed that spermatogonia-related genes (e.g., Plzf, Id4, Setdb1, Stra8, Tial1/Tiar, Bcas2, Ddx5, Srsf10, Uhrf1, and Bud31) were bound by SRSF1 in the mouse testes. Specific deletion of Srsf1 in mouse germ cells impairs homing of precursor SSCs leading to male infertility. Whole-mount staining data showed the absence of germ cells in the testes of adult conditional knockout (cKO) mice, which indicates Sertoli cell-only syndrome (SCOS) in cKO mice. The expression of spermatogonia-related genes (Gfra1, Pou5f1, Plzf, Dnd1, Stra8, and Taf4b) was significantly reduced in the testes of cKO mice. Moreover, multiomics analysis suggests that SRSF1 may affect survival of spermatogonia by directly binding and regulating Tial1/Tiar expression through AS. In addition, immunoprecipitation mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP) data showed that SRSF1 interacts with RNA splicing-related proteins (SART1, RBM15, and SRSF10). Collectively, our data reveal the critical role of SRSF1 in spermatogonia survival, which may provide a framework to elucidate the molecular mechanisms of the posttranscriptional network underlying homing of precursor SSCs.

developmental biology↗

Construction of a multi-tissue cell atlas reveals cell-type-specific regulation of molecular and complex phenotypes in pigs

The systematic characterization of cellular heterogeneity among tissues and cell-type-specific regulation underlying complex phenotypes remains elusive in pigs. Within the Pig Genotype-Tissue Expression (PigGTEx) project, we present a single-cell transcriptome atlas of adult pigs encompassing 229,268 high-quality nuclei from 19 tissues, annotated to 67 major cell types. Besides cellular heterogeneity within and across tissues, we further characterize prominent tissue-specific features and functions of muscle, epithelial, and immune cells. Through deconvoluting 3,921 bulk RNA-seq samples from 17 matching tissues, we dissect thousands of genetic variants with cell-type interaction effects on gene expression (ieQTL). By colocalizing these ieQTL with variants associated with 268 complex traits, we provide new insights into the cellular mechanisms behind these traits. Moreover, we highlight that orthologous genes with cell-type-specific regulation in pigs exhibit significant heritability enrichment for some human complex phenotypes. Altogether, our work provides a valuable resource and highlights novel insights in cellular regulation of complex traits for accelerating pig precision breeding and human biomedical research.

genetics↗

Design-Rules for Stapled Alpha-Helical Peptides with On-Target In Vivo Activity: Application toMdm2/X dual antagonists

Stapled -helical peptides can bind to and modulate historically intractable targets while addressing the traditional liabilities associated with peptide therapeutics. However, their pipeline advancement has been impeded by the challenges of identifying peptides with sufficient cellular uptake to engage the target protein while lacking off-target toxicities. Here, we advance the field to arrive at a workflow for identifying advanced stapled peptide lead molecules with on-target in vivo activity with no off-target cell proliferation effects. Specifically, we generated a >350-member library based on ATSP-7041, a stapled peptide Mdm2(X) antagonist with validated on-target cellular effects but with significant off-target activity. Key insights from library analysis include 1) a clear correlation between lipophilicity and permeability, 2) removal of positive charge to avoid off-target toxicities, 3) judicious placement of anionic residues to enhance peptide solubility/behavior, 4) optimization of C-terminal length and helicity to enhance cell activity, 5) optimization of staple type/number to avoid polypharmacology. Incorporation of one or more of these attributes led to molecules with improved in vitro and in vivo activities (up to a >292x improved cell proliferation EC50). A subset of peptides were devoid of off-target cell proliferation effects in cell lines lacking wild-type p53 protein (up to a >3800x on-target index). This latter improvement contrasted with clinical Mdm2 antagonistic molecules. Application of these design rules to a distinct Mdm2(X) peptide series resulted in rapid improvement in cellular activity (>150x) and removal of off-target toxicities. Overall, the detailed workflow outlined here should help researchers identify stapled -helical peptides for therapeutic impact.

biochemistry↗

Comprehensive characterization of tumor microenvironment in colorectal cancer via histopathology-molecular analysis

PurposeTo explain how the tumor microenvironment (TME) contributes to biological and clinical heterogeneity of colorectal cancer (CRC). MethodsUsing multi-omics analysis, single cell transcriptomic sequencing analysis and artificial intelligence-enabled spatial analysis of whole-slide images, we performed a comprehensive characterization of TME in colorectal cancer (CCCRC). ResultsCRC samples were classified into four CCCRC subtypes with distinct TME features, namely, C1 as the proliferative subtype with low immunogenicity; C2 as the immunosuppressed subtype with the terminally exhausted immune characteristics; C3 as the immune-excluded subtype with the distinct upregulation of stromal components and a lack of T cell infiltration in tumor core; and C4 as the immunomodulatory subtype with the remarkable upregulation of anti-tumor immune components. The four CCCRC subtypes had distinct histopathological and molecular characteristics, therapeutic efficacy, and prognosis. The C1 subtype was more sensitive to chemotherapy, the C2 and C3 subtypes were more sensitive to WNT pathway inhibitor SB216763 and Hedgehog pathway inhibitor vismodegib, and the C4 subtype was suitable for ICB treatment. Finally, we established a single-sample gene classifier for identifying the CCCRC subtypes. ConclusionsOur integrative analyses ultimately established a holistic framework to thoroughly dissect the TME of CRC, and the CCCRC classification system with high biological interpretability might facilitate biomarker discoveries and clinical treatment decisions in the future.

cancer biology↗

scMINER: a mutual information-based framework for identifying hidden drivers from single-cell omics data

The sparse nature of single-cell omics data makes it challenging to dissect the wiring and rewiring of the transcriptional and signaling drivers that regulate cellular states. Many of the drivers, referred to as "hidden drivers", are difficult to identify via conventional expression analysis due to low expression and inconsistency between RNA and protein activity caused by post-translational and other modifications. To address this issue, we developed scMINER, a mutual information (MI)-based computational framework for unsupervised clustering analysis and cell-type specific inference of intracellular networks, hidden drivers and network rewiring from single-cell RNA-seq data. We designed scMINER to capture nonlinear cell-cell and gene-gene relationships and infer driver activities. Systematic benchmarking showed that scMINER outperforms popular single-cell clustering algorithms, especially in distinguishing similar cell types. With respect to network inference, scMINER does not rely on the binding motifs which are available for a limited set of transcription factors, therefore scMINER can provide quantitative activity assessment for more than 6,000 transcription and signaling drivers from a scRNA-seq experiment. As demonstrations, we used scMINER to expose hidden transcription and signaling drivers and dissect their regulon rewiring in immune cell heterogeneity, lineage differentiation, and tissue specification. Overall, activity-based scMINER is a widely applicable, highly accurate, reproducible and scalable method for inferring cellular transcriptional and signaling networks in each cell state from scRNA-seq data. The scMINER software is publicly accessible via: https://github.com/jyyulab/scMINER.

systems biology↗

RabbitTClust: enabling fast clustering analysis of millions bacteria genomes with MinHash sketches

We present RabbitTClust, a fast and memory-efficient genome clustering tool based on sketch-based distance estimation. Our approach enables efficient processing of large-scale datasets by combining dimensionality reduction techniques with streaming and parallelization on modern multi-core platforms. 113,674 complete bacterial genome sequences (RefSeq: 455 GB in FASTA format) can be clustered within less than 6 minutes and 1,009,738 GenBank assembled bacterial genomes (4.0 TB in FASTA format) within only 34 minutes on a 128-core workstation. Our results further identify 1,269 repetitive genomes (identical nucleotide content) in RefSeq bacterial genomes.

bioinformatics↗

LINC01184 is highly expressed and functions as a tumor-promotive factor in hepatocellular carcinoma

The expression and function of LINC01184 in hepatocellular carcinoma are unknown. We analyzed the changes in LINC01184 expression in hepatocellular carcinoma using public data, and also analyzed the relationship between LINC01184 and patient prognosis. In vitro, we investigated the effect of LINC01184 on HCC cell growth using cell activity analysis, clone formation analysis, and regulatory death analysis. We also explored the effect of LINC01184 on HCC cell migration using transwell analysis and scratch assay. We found that LINC01184 was significantly highly expressed in hepatocellular carcinoma tissues. Patients with high LINC01184 levels had poorer overall survival and disease-free survival. knockdown of LINC01184 in HUH7 and PLC/PRF/5 cells inhibited cell proliferation and induced regulatory death. Down-regulation of LINC01184 also leads to a reduction in the migratory capacity of cells. In conclusion, LINC01184 may become a biomarker or a new therapeutic target for HCC.

cancer biology↗

LINC02428, a liver-specific long noncoding RNA suppresses hepatocellular carcinoma progression

There is growing evidence that lncRNAs play an important role in the progression of HCC, especially liver-specific expression of lncRNAs. LINC02428 is a liver-specific labeled lncRNA, but its role in HCC is unclear. We investigated the expression characteristics of LINC02428 in hepatocellular carcinoma tissues and analyzed its function in HCC. Using TCGA public data we found that the expression level of LINC02428 was significantly reduced in hepatocellular carcinoma tissues, compared to normal tissues. LINC02428 was also significantly reduced in hepatocellular carcinoma tissues in our cDNA microarray data from HCC patients. Survival analysis suggests that HCC patients with lower LINC02428 have a lower overall survival rate. In an in vitro analysis, overexpression of LINC02428 inhibited HCC cell proliferation, migration, and induced apoptosis. In conclusion, we report for the first time the expression profile of a liver-specific lncRNA, LINC02428, in HCC and confirmed its ability to inhibit the progression of HCC. LINC02428 may become a new target for the diagnosis and treatment of HCC.

cancer biology↗

DOTA chelation through click chemistry enables favorable biodistribution of 89Zr-radiolabeled antibodies: A comparison with DFO chelation

Currently, the DFO chelator is commonly used to conjugate monoclonal antibodies (mAbs) and 89Zr, whereas the DOTA chelator is commonly used to conjugate mAbs and alpha- and beta-emitting metal radionuclides. However, if the degradation of [89Zr]Zr-DFO-mAb is not negligible, the in vivo biodistribution of 89Zr might not reflect that of metal radionuclides conjugated with DOTA-mAb. We hypothesized that [89Zr]Zr-DOTA-mAb as a new imaging counterpart would accurately predict the biodistribution of therapeutic metal radionuclides delivered by DOTA-mAb. In this study, we prepared [89Zr]Zr-DOTA-trastuzumab for the first time by a two-step reaction using click chemistry and then investigated the differences in biodistribution profiles between two chelating approaches for 89Zr. MethodsWe prepared [89Zr]Zr-DOTA-trastuzumab from DOTA-tetrazine conjugates (DOTA-Tz) and transcyclooctene-trastuzumab conjugates (TCO-trastuzumab). We first radiolabeled DOTA-Tz with 89Zr in a reaction solution of MeOH and HEPES buffer and then used a click reaction to obtain [89Zr]Zr-DOTA-Tz/TCO-trastuzumab. We performed biodistribution studies and PET imaging with [89Zr]Zr-DOTA-trastuzumab in a mouse model of HER2-positive ovarian cancer, SKOV3 xenograft mice at 24, 72, and 144 hours post-injection and compared these data with those of [89Zr]Zr-DFO-trastuzumab. ResultsTCO-trastuzumab was radiolabeled with [89Zr]Zr-DOTA-Tz in the two-step reaction in good radiochemical yield (57.8 {+/-} 17.6%). HER2-positive tumors were clearly visualized with [89Zr]Zr-DOTA-trastuzumab in PET imaging studies. The temporal profile changes of 89Zr radioactivity in SKOV3 tumors and bone marrow were sufficiently different between [89Zr]Zr-DOTA-trastuzumab and [89Zr]Zr-DFO-trastuzumab (P < 0.05). Conclusion: [89Zr]Zr-DOTA-trastuzumab can be produced by the two-step radiolabeling reaction based on the Tz/TCO click reaction. Presumably, 89Zr released from DFO is not negligible. In contrast, [89Zr]Zr-DOTA-mAb would better predict the biodistribution of [177Lu]Lu- or [225Ac]Ac-DOTA-mAb than [89Zr]Zr-DFO-mAb, thus avoiding the use of different chelator for 89Zr at the expense of the click chemistry step. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=102 SRC="FIGDIR/small/507067v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@d7256borg.highwire.dtl.DTLVardef@d9d3d5org.highwire.dtl.DTLVardef@e24d97org.highwire.dtl.DTLVardef@1541bf0_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

Modeling spatial intercellular communication and multilayer signaling regulations using stMLnet

Multicellular organisms require intercellular and intracellular signaling to coordinately regulate different cell functions. Although many methods of cell-cell communication (CCC) inference have been developed, they seldom account for both the intracellular signaling responses and global spatial information. The recent advancement of spatial transcriptomics (ST) provides unprecedented opportunities to better decipher CCC signaling and functioning. In this paper, we propose an ST-based multilayer network method, stMLnet, for inferring spatial intercellular communication and multilayer signaling regulations by quantifying distance-weighted ligand-receptor signaling activity based on diffusion and mass action models and mapping it to intracellular targets. We benchmark stMLnet with existing methods using simulation data and 8 real datasets of cell type-specific perturbations. Furthermore, we demonstrate the applicability of stMLnet on six ST datasets acquired with four different technologies (e.g., seqFISH+, Slide-seq v2, MERFIS and Visium), showing its effectiveness and reliability on ST data with varying spatial resolutions and gene coverages. Finally, stMLnet identifies positive feedback circuits between alveolar epithelial cells, macrophages, and monocytes via multilayer signaling pathways within a COVID-19 microenvironment. Our proposed method provides an effective tool for predicting multilayer signaling regulations between interacting cells, which can advance the mechanistic and functional understanding of spatial CCCs.

systems biology↗

Processing Stage Flexibility of the SNARC effect: Task Relevance or Magnitude Relevance?

Previous studies have shown that the processing stage of the spatial-numerical association of response codes (SNARC) effect was flexible. Two recent studies by Nan et al. (2021) and Yan et al. (2021) used the same experimental paradigm to check whether the SNARC effect occurred in the semantic-representation stage but reached contradictory conclusions, showing that the SNARC effect was influenced by a magnitude Stroop effect in a magnitude comparison task but not by a parity Stroop effect in a parity judgment task. The two studies had two distinct operational factors: the task type (magnitude comparison task or parity judgment task, with the numerical magnitude information task-relevant or task-irrelevant) and the semantic representation stage-related interference information (magnitude or parity Stroop effect, with the interference information magnitude-relevant or magnitude-irrelevant). To determine which factor influenced the SNARC effect, in the present study, the Stroop effect was switched in the two tasks based on the previous studies. The findings of four experiments consistently showed that the SNARC effect was not influenced by the parity Stroop effect in the magnitude comparison task but was influenced by the magnitude Stroop effect in the parity judgment task. Combined with the results of Nan et al. (2021) and Yan et al. (2021), the findings indicated that regardless of the task type or the task-relevance of numerical magnitude information, magnitude-relevant interference information was the primary factor to affect the SNARC effect. Furthermore, a two-stage processing model that explained the observed flexibility of the SNARC effect was proposed and discussed. Public Significance StatementPrevious studies have shown that the spatial-numerical association of response codes (SNARC) effect is flexible in the direction and processing stage. The task type and interference information might be two influential factors for the flexibility of the SNARC effect. The present study reported that magnitude-relevant interference information, regardless of task type, was a crucial role to affect the SNARC effect. Moreover, a two-stage processing model was proposed to reveal the processing pathway of the SNARC effect and provided a possible explanation for the longstanding debate about the processing stage of the SNARC effect.

animal behavior and cognition↗

Rhamnan Sulfate Reduces Atherosclerotic Plaque Formation and Vascular Inflammation

ObjectiveWhile lipid-lowering drugs have become a mainstay of clinical therapy these treatments only slow the progression of the disease and can have side effects. Thus, new treatment options are needed to supplement the effects of lipid lowering therapy for treating atherosclerosis. We examined the use of an inexpensive and widely available marine polysaccharide rhamnan sulfate as an oral therapeutic for limiting vascular inflammation and atherosclerosis. Methods and ResultsWe found rhamnan sulfate enhanced the barrier function of endothelial cells, preventing the deposition of LDL and maintaining barrier function even in the presence of glycocalyx-degrading enzymes. Rhamnan sulfate was also found to bind directly to FGF-2, PDGF-BB and NF-{kappa}B subunits with high affinity. In addition, rhamnan sulfate was a potent inhibitor of NF-{kappa}B pathway activation in endothelial cells by TNF-. We treated ApoE-/- mice with a high fat diet for 4 weeks and then an addition 9 weeks of high fat diet with or without rhamnan sulfate. Rhamnan sulfate reduced vascular inflammation and atherosclerosis in both sexes of ApoE-/- mice but had a stronger therapeutic effect in female mice. Oral consumption of rhamnan sulfate induced a significant decrease in cholesterol plasma levels in female mice but not in male mice. ConclusionsRhamnan sulfate has beneficial effects in reducing inflammation, binding growth factors and NF-{kappa}B, enhancing endothelial barrier function and reducing atherosclerotic plaque formation in ApoE-/- mice.

physiology↗