UNASSIGNED: Antibody-mediated rejection (ABMR) significantly affects transplanted kidney survival, yet the macrophage phenotype, ontogeny, and mechanisms in ABMR remain unclear.
UNASSIGNED: We analyzed post-transplant sequencing and clinical data from GEO and ArrayExpress. Using dimensionality reduction and clustering on scRNA-seq data, we identified macrophage subpopulations and compared their infiltration in ABMR and non-rejection cases. Cibersort quantified these subpopulations in bulk samples. Cellchat, SCENIC, monocle2, and monocle3 helped explore intercellular interactions, predict transcription factors, and simulate differentiation of cell subsets. The Scissor method linked macrophage subgroups with transplant prognosis. Furthermore, hdWGCNA, nichnet, and lasso regression identified key genes associated with core transcription factors in selected macrophages, validated by external datasets.
UNASSIGNED: Six macrophage subgroups were identified in five post-transplant kidney biopsies. M1-like infiltrating macrophages, prevalent in ABMR, correlated with pathological injury severity. MIF acted as a primary intercellular signal in these macrophages. STAT1 regulated monocyte-to-M1-like phenotype transformation, impacting transplant prognosis via the IFNγ pathway. The prognostic models built on the upstream and downstream genes of STAT1 effectively predicted transplant survival. The TLR4-STAT1-PARP9 axis may regulate the pro-inflammatory phenotype of M1-like infiltrating macrophages, identifying PARP9 as a potential target for mitigating ABMR inflammation.
UNASSIGNED: Our study delineates the macrophage landscape in ABMR post-kidney transplantation, underscoring the detrimental impact of M1-like infiltrating macrophages on ABMR pathology and prognosis.

UNASSIGNED: It is essential to acknowledge that the cardiovascular toxicity associated with anthracycline drugs can be partially attributed to the damage inflicted on blood vessels and endothelial cells. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have the potential to repair cellular processes and promote tissue regeneration through the transfer of signaling molecules such as miRNAs. In the present study, we investigated the effects of MSC-EVs on daunorubicin (DNR)-damaged human cardiac microvascular endothelial cells (HCMEC) and developing blood vessels of Chicken Chorioallantoic Membrane (CAM) in vivo.
UNASSIGNED: We constructed in vitro and in vivo models of DNR-damaged endothelial cells and developing blood vessel. Scratch wound assays, EdU assays, tube formation assays, and SA-β-Gal staining were used to evaluate the effects of MSC-EVs on cell migration, proliferation, angiogenesis capacity and cell senescence. Blood vessel area was used to assess the effects of MSC-EVs on CAM vasculature. RT-qPCR was used to detect the mRNA expression levels of inflammatory molecules. RNA sequencing was employed to compare differential gene expression and downstream regulatory mechanisms. RNA interference experiments and miRNA mimic overexpression experiments were used to validate the regulatory effects of target genes and downstream signaling pathways.
UNASSIGNED: We found that MSC-EVs improved the migration, proliferation, and angiogenesis of HCMEC, while also alleviating cellular senescence. The angiogenic effect on the developing blood vessels was confirmed in vivo. We identified that MSC-EVs downregulated the expression of PARP9, thereby inhibiting the STAT1/pSTAT1 signaling pathway. This downregulation effect is likely mediated by the transfer of miR-186-5p from MSC-EVs to HCMEC. Overexpression of miR-186-5p in DNR-damaged HCMEC also exhibited the aforementioned downregulation effect. In vivo, the introduction of miR-186-5p mimics enhanced angiogenesis in the CAM model.
UNASSIGNED: To summarize, our study reveals that MSC-EVs can restore the cellular function of DNR-damaged HCMEC and alleviate cellular senescence through the miR-185-5p-PARP9-STAT1/pSTAT1 pathway. This finding highlights the potential of MSC-EVs as a therapeutic strategy for mitigating the detrimental effects of anthracycline-induced endothelial damage.

UNASSIGNED: Studies have shown that Nicotinamide adenine dinucleotide (NAD+) metabolism can promote the occurrence and development of glioma. However, the specific effects and mechanisms of NAD+ metabolism in glioma are unclear and there were no systematic researches about NAD+ metabolism related genes to predict the survival of patients with glioma.
UNASSIGNED: The research was performed based on expression data of glioma cases in the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Firstly, TCGA-glioma cases were classified into different subtypes based on 49 NAD+ metabolism-related genes (NMRGs) by consensus clustering. NAD+ metabolism-related differentially expressed genes (NMR-DEGs) were gotten by intersecting the 49 NMRGs and differentially expressed genes (DEGs) between normal and glioma samples. Then a risk model was built by Cox analysis and the least shrinkage and selection operator (LASSO) regression analysis. The validity of the model was verified by survival curves and receiver operating characteristic (ROC) curves. In addition, independent prognostic analysis of the risk model was performed by Cox analysis. Then, we also identified different immune cells, HLA family genes and immune checkpoints between high and low risk groups. Finally, the functions of model genes at single-cell level were also explored.
UNASSIGNED: Consensus clustering classified glioma patients into two subtypes, and the overall survival (OS) of the two subtypes differed. A total of 11 NAD+ metabolism-related differentially expressed genes (NMR-DEGs) were screened by overlapping 5,995 differentially expressed genes (DEGs) and 49 NAD+ metabolism-related genes (NMRGs). Next, four model genes, PARP9, BST1, NMNAT2, and CD38, were obtained by Cox regression and least absolute shrinkage and selection operator (Lasso) regression analyses and to construct a risk model. The OS of high-risk group was lower. And the area under curves (AUCs) of Receiver operating characteristic (ROC) curves were >0.7 at 1, 3, and 5 years. Cox analysis showed that age, grade G3, grade G4, IDH status, ATRX status, BCR status, and risk Scores were reliable independent prognostic factors. In addition, three different immune cells, Mast cells activated, NK cells activated and B cells naive, 24 different HLA family genes, such as HLA-DPA1 and HLA-H, and 8 different immune checkpoints, such as ICOS, LAG3, and CD274, were found between the high and low risk groups. The model genes were significantly relevant with proliferation, cell differentiation, and apoptosis.
UNASSIGNED: The four genes, PARP9, BST1, NMNAT2, and CD38, might be important molecular biomarkers and therapeutic targets for glioma patients.

Gastroenteritis is inflammation of the lining of stomach and intestines and causes significant morbidity and mortality worldwide. Many viruses, especially RNA viruses are the most common cause of enteritis. Innate immunity is the first line of host defense against enteric RNA viruses and virus-induced intestinal inflammation. The first layer of defense against enteric RNA viruses in the intestinal tract is intestinal epithelial cells (IECs), dendritic cells and macrophages under the intestinal epithelium. These innate immune cells express pathogen-recognition receptors (PRRs) for recognizing enteric RNA viruses through sensing viral pathogen-associated molecular patterns (PAMPs). As a result of this recognition type I interferon (IFN), type III IFN and inflammasome activation occurs, which function cooperatively to clear infection and reduce viral-induced intestinal inflammation. In this review, we summarize recent findings about mechanisms involved in enteric RNA virus-induced intestinal inflammation. We will provide an overview of the enteric RNA viruses, their RNA sensing mechanisms by host PRRs, and signaling pathways triggered by host PRRs, which shape the intestinal immune response to maintain intestinal homeostasis.

Glioma is a primary malignancy of the central nervous system (CNS). As biomedicine advances, an efficient molecular target is urgently needed for the diagnosis and treatment of glioma. Meanwhile, several studies have demonstrated that glioma development is closely related to immunity. PARP9 is an inactive mono-ADP-ribosyltransferase belonging to the poly-ADP ribosyltransferase (ARTD) family. In this article, we aimed to reveal the relationship between PARP9 and glioma and explore the potential prognostic value and immunotherapeutic targetability of PARP9 in glioma.
PARP9 transcript levels were analyzed with TCGA and GEO databases. The clinicopathological information of patients with glioma in the TCGA database and gene expression profiles were analyzed to determine the relationship between the expression of PARP9 and clinicopathologic characteristics. Kaplan-Meier survival analysis, univariate Cox regression analysis, and multivariate Cox regression analysis were used for survival analysis. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used for bioinformatics analysis. Correlation analysis explored the relationships between PARP9, infiltrating inflammatory immune cells, and immune checkpoint molecules.
PARP9 is highly expressed in glioma, and high expression of PARP9 is associated with poor prognosis and advanced clinicopathological features. Bioinformatics analysis showed that some immune-related pathways were closely associated with high expression of PARP9. Correlation analysis indicated that PARP9 was closely related to inflammatory and immune responses, high immune cell infiltration, and immune checkpoint molecules.
PARP9 may serve as an unfavorable prognosis predictor for glioma and a potential immunotherapeutic target.

Long noncoding RNA (lncRNA) small nucleolar RNA host gene 16 (SNHG16) has been linked to multiple cancers including breast, ovarian, bladder, and colorectal cancer. However, the role of SNHG16 in cervical cancer is unclear. Here, quantitative analysis of SNHG16 and PARP9 expression levels in cervical cancer tissues and cell lines indicated that both SNHG16 and PARP9 were highly expressed compared with controls. Using the dual-luciferase reporter gene assay, RNA immunoprecipitation, chromatin immunoprecipitation, we were able to determine that SNHG16 recruited SPI1 protein to promote transcription of PARP9 to upregulate its transcription in cervical cancer cells. After ectopic expression and knockdown experiments were conducted, it was observed that silencing SNHG16 inhibited PARP9 expression, proliferation, and invasion of cervical cancer cells, which was rescued by co-transfection of SNHG16 silencing and PARP9 overexpression. Moreover, in vivo experimental results showed that silencing SNHG16 reduced the expression of PARP9 and suppressed tumor growth. These data indicate that SNHG16 recruits SPI1 to upregulate PARP9, which promotes the tumorigenicity of cervical cancer cells. The regulation of their expression might provide a new direction for treating cervical cancer.