Anti-GSTP1 pAb

作者單位：北京大學(xué)化學(xué)與分子工程學(xué)院，北京分子科學(xué)國(guó)家實(shí)驗(yàn)室，合成與功能生物分子中心

摘要：Hyperhomocysteinemia (HHcy) is a risk factor for chronic kidney diseases (CKDs) that affects about 85% CKD patients. HHcy stimulates B cells to secrete pathological antibodies, although it is unknown whether this pathway mediates kidney injury. In HHcy-treated 2-kidney, 1-clip (2K1C) hypertensive murine model, HHcy-activated B cells secreted anti-beta 2 glycoprotein I (β2GPI) antibodies that deposited in glomerular endothelial cells (GECs), exacerbating glomerulosclerosis and reducing renal function. Mechanistically, HHcy 2K1C mice increased phosphatidylethanolamine (PE) (18:0/20:4, 18:0/22:6, 16:0/20:4) in kidney tissue, as determined by lipidomics. GECs oxidative lipidomics validated the increase of oxidized phospholipids upon Hcy-activated B cells culture medium (Hcy-B CM) treatment, including PE (18:0/20:4?+?3[O], PE (18:0a/22:4?+?1[O], PE (18:0/22:4?+?2[O] and PE (18:0/22:4?+?3[O]). PE synthases ethanolamine kinase 2 (etnk2) and ethanolamine-phosphate cytidylyltransferase 2 (pcyt2) were increased in the kidney GECs of HHcy 2K1C mice and facilitated polyunsaturated PE synthesis to act as lipid peroxidation substrates. In HHcy 2K1C mice and Hcy-B CM-treated GECs, the oxidative environment induced by iron accumulation and the insufficient clearance of lipid peroxides caused by transferrin receptor (TFR) elevation and down-regulation of SLC7A11/glutathione peroxidase 4 (GPX4) contributed to GECs ferroptosis of the kidneys. In vivo, pharmacological depletion of B cells or inhibition of ferroptosis mitigated the HHcy-aggravated hypertensive renal injury. Consequently, our findings uncovered a novel mechanism by which B cell-derived pathogenic anti-β2GPI IgG generated by HHcy exacerbated hypertensive kidney damage by inducing GECs ferroptosis. Targeting B cells or ferroptosis may be viable therapeutic strategies for ameliorating lipid peroxidative renal injury in HHcy patients with hypertensive nephropathy.

作者單位：美國(guó)休斯頓德克薩斯大學(xué)健康科學(xué)中心麥戈文醫(yī)學(xué)院綜合生物學(xué)和藥理學(xué)系

摘要：N6-methyladenosine (m⁶A), one of the most prevalent mRNA modifications in eukaryotes, plays a critical role in modulating both biological and pathological processes. However, it is unknown whether mutant p53 neomorphic oncogenic functions exploit dysregulation of m⁶A epitranscriptomic networks. Here, we investigate Li-Fraumeni syndrome (LFS)-associated neoplastic transformation driven by mutant p53 in iPSC-derived astrocytes, the cell-of-origin of gliomas. We find that mutant p53 but not wild-type (WT) p53 physically interacts with SVIL to recruit the H3K4me3 methyltransferase MLL1 to activate the expression of m⁶A reader YTHDF2, culminating in an oncogenic phenotype. Aberrant YTHDF2 upregulation markedly hampers expression of multiple m⁶A-marked tumor-suppressing transcripts, including CDKN2B and SPOCK2, and induces oncogenic reprogramming. Mutant p53 neoplastic behaviors are significantly impaired by genetic depletion of YTHDF2 or by pharmacological inhibition using MLL1 complex inhibitors. Our study reveals how mutant p53 hijacks epigenetic and epitranscriptomic machinery to initiate gliomagenesis and suggests potential treatment strategies for LFS gliomas. 

Anti-Met Enkephalin pAb | FCM

文獻(xiàn)引用抗體：

bs-14165R; Anti-CYP8B1 pAb | IHC

作者單位：中國(guó)重慶軍醫(yī)大學(xué)新橋醫(yī)院消化內(nèi)科

摘要：Intrahepatic cholestasis of pregnancy (ICP) is a female pregnancy-specific disorder that is characterized by increased serum bile acid and adverse fetal outcomes. The aetiology and mechanism of ICP are poorly understood; thus, existing therapies have been largely empiric. Here we show that the gut microbiome differed significantly between individuals with ICP and healthy pregnant women, and that colonization with gut microbiome from ICP patients was sufficient to induce cholestasis in mice. The gut microbiomes of ICP patients were primarily characterized by Bacteroides fragilis (B. fragilis), and B. fragilis was able to promote ICP by inhibiting FXR signaling via its BSH activity to modulate bile acid metabolism. B. fragilis-mediated FXR signaling inhibition was responsible for excessive bile acid synthesis and interrupted hepatic bile excretion to ultimately promote the initiation of ICP. We propose that modulation of the gut microbiota-bile acid-FXR axis may be of value for ICP treatment.