Bone marrow-derived mesenchymal stem cells (MSCs) are key components of the hematopoietic microenvironment and provide support to hematopoiesis and modulate immune system. Several studies suggest that SLE may be seen as stem cell disorders. However, it is unclear that whether MSCs from SLE patients are defective. So in this research, we studied the biological character of bone marrow derived MSCs in patients with SLE, focused on their phenotype (morphology and immunophenotype), karyotype, cytokines expression and hematopoietic support of MSCs. Our results showed that MSCs from SLE patients and normal controls can be successfully culture-expanded, but the MSCs from SLE grew more slowly than those of normal controls (P < 0.05). Cells from both groups were positive for CD29, CD44 and CD105, and negative for CD14, CD34, CD45 and HLA-DR. MSCs from SLE have a normal karyotype. Both groups express IL-6, IL7, IL-11, macrophage colony stimulating factor (M-CSF) and stem cell factor (SCF) at mRNA level. While IL-6 and IL-7 were down-regulated in MSCs from SLE patient (P < 0.05) at mRNA level. The MSCs from SLE patients and normal controls were infused into ICR (Tac: Icr: Ha strain) mice after high-dose chemotherapy, with no adverse events in either group. Recovery of white blood cells, hemoglobin and platelet was more rapid (P < 0.05) compared with the group without MSCs infusion. We conclude that MSCs in patient with SLE have abnormalities compared with those in normal control. MSCs in patient with SLE may play an important role in the SLE pathogenesis.

Sympathetic outflow is increased in hypertension. The aim of the present study was to investigate whether the cardiac sympathetic afferent reflex (CSAR) is enhanced in two-kidney one-clip (2K1C) renovascular hypertensive rats, and whether the enhanced CSAR contributes, in part, to the increased sympathetic outflow. Furthermore, the role of central angiotensin II type 1 (AT 1 ) receptors in mediating the CSAR was determined. Under urethane and α-chloralose anaesthesia, the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in sinoaortic denervated and cervical vagotomized rats. The CSAR was evaluated by the response of RSNA and MAP to epicardial application of 1.0 nmol of capsaicin. Compared with shamoperated rats, the CSAR, baseline RSNA and plasma noradrenaline level were significantly enhanced in 2K1C rats. Intrapericardial administration of resiniferatoxin, which abolishes the CSAR because of the desensitization of transient receptor potential vanilloid 1-containing cardiac afferent fibres, decreased the RSNA and MAP. The enhanced CSAR in 2K1C rats was normalized by intracerebroventricular administration of the AT 1 receptor antagonist losartan. Intracerebroventricular administration of angiotensin II further potentiated the enhanced CSAR in 2K1C rats, a response which was abolished by pretreatment with losartan. These results indicate that the CSAR is enhanced in 2K1C rats and the enhanced CSAR contributes, in part, to the sympathetic activation and hypertension. Central AT 1 receptors are involved in the enhanced CSAR in 2K1C rats.

Delineating the protein network associated with long non-coding RNAs (lncRNAs) is fundamental to understanding the functional mechanisms of lncRNAs. Current methods to identify lncRNA-binding proteins either rely on crosslinking-mediated complex co-precipitation or require extensive molecular engineering, leading to drawbacks such as loss of cellular context and low capture e ciency. Here we describe a CRISPR-Assisted RNA-Protein Interaction Detection method (CARPID), which leverages CRISPR/CasRx-based RNA targeting and proximity labeling, to rapidly capture binding proteins of speci c lncRNAs in their native cellular context followed by LC-MS/MS identi cation. Applied to a variety of lncRNAs of different lengths and subcellular localizations, CARPID is proven to be a reliable and robust tool to discover the binding proteins of lncRNAs inside living cells.

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