cholesterol-stearamide-mediate-lymphocyte-apoptosis-cytokine

Cholesterol and Stearamide Mediate Lymphocyte Apoptosis and Cytokine Secretion in Systemic Lupus Erythematosus

Alterations in serum metabolite composition have been increasingly associated with systemic lupus erythematosus (SLE), yet the direct effects of these ...

Anhui University of Science & Technology

Transfusion of red blood cells (RBCs) from ABO-matched but genetically unrelated donors is commonly used for treating anemia and acute blood loss. Increasing demand and insufficient supply for donor RBCs, especially those of universal blood types or free of known and unknown pathogens, has called for ex vivo generation of functional RBCs by large-scale cell culture. However, generating physiological numbers of transfusable cultured RBCs (cRBCs) ex vivo remains challenging, due to our inability to either extensively expand primary RBC precursors (erythroblasts) or achieve efficient enucleation once erythroblasts have been expanded and induced to differentiation and maturation. Here, we report that ectopic expression of the human BMI1 gene confers extensive expansion of human erythroblasts, which can be derived readily from adult peripheral blood mononuclear cells of either healthy donors or sickle cell patients. These extensively expanded erythroblasts (E3s) are able to proliferate exponentially (>1 trillion-fold in 2 months) in a defined culture medium. Expanded E3 cells are karyotypically normal and capable of terminal maturation with approximately 50% enucleation. Additionally, E3-derived cRBCs can circulate in a mouse model following transfusion similar to primary human RBCs. Therefore, we provide a facile approach of generating physiological numbers of human functional erythroblasts ex vivo.

BMI1 enables extensive expansion of functional erythroblasts from human peripheral blood mononuclear cells.

Spatial proteomics is a multidimensional technique that studies the spatial distribution and function of proteins within cells or tissues across both spatial and temporal dimensions. This field multidimensionally reveals the complex structure of the human proteome, including the characteristics of protein spatial distribution, dynamic protein translocation, and protein interaction networks. Recently, as a crucial method for studying protein spatial localization, spatial proteomics has been applied in the clinical investigation of various diseases. This review summarizes the fundamental concepts and characteristics of tissue-level spatial proteomics, its research progress in common human diseases such as cancer, neurological disorders, cardiovascular diseases, autoimmune diseases, and anticipates its future development trends. The aim is to highlight the significant impact of spatial proteomics on understanding disease pathogenesis, advancing diagnostic methods, and developing potential therapeutic targets in clinical research.

Spatial proteomics: unveiling the multidimensional landscape of protein localization in human diseases.

Extrachromosomal circular DNA (eccDNA) has emerged as a central focus in molecular biology, with various types being found across species through advanced techniques, including high-throughput sequencing. This dynamic molecule exerts a significant influence on aging and immune function and plays pivotal roles in autoimmune diseases, type 2 diabetes mellitus, cancer, and genetic disorders.

Exploring the Role of Extrachromosomal Circular DNA in Human Diseases.

False smut caused by  is one of the most destructive diseases in rice. The disease is primarily controlled with fungicides, leading to the development of fungicide resistance. Although spray-induced gene silencing (SIGS) has been utilized for disease management, it has not been applied to control rice false smut. In this study, we introduce a novel approach involving the  synthesis and exogenous application of double-stranded RNA (dsRNA) to manage rice false smut disease. The , , and  genes were selected as target genes and highly efficient fragments for gene silencing were identified through screening of silencing transformants. Although direct dsRNA uptake by  was not observed,  synthesis and application of dsRNA to rice effectively reduced the expression of target genes. Treatment with dsRNA targeting the genes resulted in a decrease in smut balls, providing a promising disease management strategy against rice false smut.

The Bacteria-Derived dsRNA Was Used for Spray-Induced Gene Silencing for Rice False Smut Control.

Systemic Lupus Erythematosus (SLE) is a typical autoimmune disease characterized by a complex pathogenesis and a strong genetic predisposition. The study of inflammatory response in SLE monocytes is not very clear, and exploring the inflammatory factors of monocytes is beneficial to discover new diagnostic targets.

scRNA-seq reveals involvement of monocytes in immune response in SLE patients.

Liver cirrhosis represents a critical stage of chronic liver disease, characterized by progressive liver damage, cellular dysfunction, and disrupted cell-to-cell interactions. Glycosylation, an essential post-translational modification, significantly influences cellular behavior and disease progression. Its role in cirrhosis at the single-cell level remains unclear, despite its importance.

Single-cell RNA sequencing and functional analysis reveal the role of altered glycosylation levels of hepatic macrophages in liver cirrhosis.

To explore SLE staging markers, we analyzed eccDNA in plasma using circular sequencing, comparing healthy controls (HC), active SLE (ASLE), and inactive SLE (ISLE) patients. We found higher eccDNA levels and lower GC content in ASLE and ISLE compared to healthy controls, with a negative correlation between GC content and anti-daDNA, C3, and C4 levels in SLE and HC samples. Differential expression of exon-derived eccGenes in ASLE and ISLE suggests their role in SLE development, with KEGG analysis showing enrichment in SLE-related pathways for these differentially expressed genes. By protein-protein interactions network analysis we found 9 exon-derived eccGenes that were significantly differentially expressed and scored high in both ISLE-HC and ASLE-ISLE as diagnostic criteria for differentiating different disease stages of SLE. In conclusion, the present study reveals that eccDNA length GC content as well as chromosomal distribution in ASLE, ISLE and HC suggests that with eccDNA is associated with the creation of SLE, suggesting GC count of eccDNA as a diagnostic marker for systemic lupus erythematosus. Significant changes in the abundance of eccDNA-related genes from exons such as SOS1, GAD2, BCL11B, PPT1, and GCNT3 were observed in ISLE as compared to ASLE and HC groups and were significantly correlated with SLEDAI-2K. This suggests that these exon-derived eccGenes may play a role in the development and progression of the disease. Consequently, the abundance levels of these exon-derived eccGenes could potentially assist in distinguishing different stages of SLE, beyond a confirmed diagnosis, thus serving as possible biomarkers for the condition.

Comprehensive analysis of eccDNA characteristics and associated genes expression in peripheral blood of ASLE and ISLE patients.

Phosphoproteomics, an advanced branch of molecular biology, utilizes specific techniques such as mass spectrometry, affinity chromatography, and bioinformatics analysis to explore protein phosphorylation, shedding light on the cellular mechanisms that drive various biological processes. This field has become instrumental in advancing our understanding of renal diseases, from identifying underlying mechanisms to pinpointing new therapeutic targets.

Applications and prospects of phosphoproteomics in renal disease research.

The brain is the core of the central nervous system, responsible for regulating and integrating various physiological and psychological functions. Abnormal disruptions in genes during brain development can lead to a range of neurodevelopmental disorders. In this study, we performed a systematic investigation of human fetal brain tissue from miscarriages between 8 and 17 weeks of gestation using integrated single-cell RNA sequencing (scRNA-seq) and single-cell transposase-accessible chromatin sequencing (scATAC-seq). We constructed single-cell transcriptomic and epigenomic maps of neurodevelopment, revealing key signaling pathways involved in neural cell proliferation, differentiation, and functional maturation. Through pseudotime analysis, we reconstructed the developmental trajectory of neuronal differentiation and its dynamic regulatory mechanisms. Additionally, we identified cell type-specific chromatin accessibility regions during neurogenesis and, through integrated analysis, predicted potential regulatory elements involved in the process. Overall, the single-cell multi-omics integration map constructed in this study provides valuable resources for a deeper understanding of fetal brain development, cellular heterogeneity, lineage relationships, and transcriptional regulatory networks during neurogenesis.

Article	Year
BMI1 enables extensive expansion of functional erythroblasts from human peripheral blood mononuclear cells. Molecular therapy : the journal of the American Society of Gene Therapy\| PubMed ID: 33484967	2021
Spatial proteomics: unveiling the multidimensional landscape of protein localization in human diseases. Proteome science\| PubMed ID: 39304896	2024
Exploring the Role of Extrachromosomal Circular DNA in Human Diseases. Cytogenetic and genome research\| PubMed ID: 39348807	2024
The Bacteria-Derived dsRNA Was Used for Spray-Induced Gene Silencing for Rice False Smut Control. Journal of agricultural and food chemistry\| PubMed ID: 39663150	2024
scRNA-seq reveals involvement of monocytes in immune response in SLE patients. Genomics\| PubMed ID: 39818255	2025
Single-cell RNA sequencing and functional analysis reveal the role of altered glycosylation levels of hepatic macrophages in liver cirrhosis. Journal of gastroenterology\| PubMed ID: 39888412	2025
Comprehensive analysis of eccDNA characteristics and associated genes expression in peripheral blood of ASLE and ISLE patients. Epigenetics\| PubMed ID: 40108975	2025
Applications and prospects of phosphoproteomics in renal disease research. PeerJ\| PubMed ID: 40124608	2025
Integrative Single-Cell Analysis Decodes Gene Expression and Chromatin Accessibility in the Developing Human Fetal Brain. Molecular neurobiology\| PubMed ID: 40663269	2025

Mengyao Wu

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