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Inflammatory bowel disease (IBD) refers to chronic inflammatory disorders of the gut. Ulcerative colitis (UC) and Crohn’s disease (CD) are two subtypes of IBD. Evidence suggests that the intestinal microbiota plays a role in the pathogenesis of IBD, so probiotics have garnered a lot of interest as a potential treatment or prevention for IBD. However, clinical evidence of the efficacy of probiotics is still debatable. We performed a literature review. An advanced search considered clinical studies on probiotic for IBD from inception to 2023 in PubMed, Embase, Cochrane Library, and Web of Science. In the treatment of UC with probiotics, only Escherichia coli Nissle 1917 for maintenance treatment of UC in remission, and Bifidobacterium and VSL#3 for induction of remission in patients with mild to moderately active UC have shown strong evidence. Currently, there are no definitive conclusions regarding the effectiveness of probiotics in CD. The mechanism of probiotic treatment for IBD may be related to reducing oxidative stress, repairing the intestinal barrier, regulating intestinal flora balance, and modulating intestinal immune response. Differences in the benefits of probiotics between CD and UC may be attributable to the different lesion extent and immune-mediated pathophysiology. More robust randomized clinical trials are required to validate the efficacy and safety of diverse probiotic strains in IBD.

Vascular inflammation induced by angiotensin II-1 receptor autoantibody (AT1-AA) is involved in the occurrence and development of various cardiovascular diseases. miR-339-3p is closely related to the degree of vasodilation of aortic aneurysm and is also involved in the occurrence and development of acute pancreatitis. However, it is still unclear whether miR-339-3p influences AT1-AA-induced vascular inflammation. In this study, the role and mechanism of miR-339-3p in AT1-AA-induced vascular inflammation are studied. RT-PCR detection shows that the miR-339-3p levels in the thoracic aorta and serum exosomes of AT1-AA-positive rats are significantly increased. The miRwalk database predicts the mRNAs that miR-339-3p can bind to their 5′UTR. Subsequently, it is found that the number of genes contained in the T cell receptor pathway is high through KEGG analysis, and NFATc3 among them can promote the secretion of various inflammatory cytokines. AT1-AA-induced upregulation of miR-339-3p expression in vascular smooth muscle cells (VSMCs) can lead to a significant increase in NFATc3 protein level and promote vascular inflammation. Inhibition of miR-339-3p with antagomir-339-3p can significantly reverse AT1-AA-induced high expressions of IL-6, IL-1β and TNF-α proteins in rat thoracic aorta and VSMCs. That is, AT1-AA can upregulate the expression of miR-339-3p in VSMCs, and the increased miR-339-3p targets the 5′UTR of NFATc3 mRNA to increase the protein level of NFATc3, thereby aggravating the occurrence of vascular inflammation. These findings provide new experimental evidence for the involvement of miRNAs in regulating vascular inflammatory diseases.

The large-conductance calcium-activated potassium (BK) channel is a critical regulator and potential therapeutic target of vascular tone and architecture, and abnormal expression or dysfunction of this channel is linked to many vascular diseases. Vascular remodelling is the early pathological basis of severe vascular diseases. Delaying the progression of vascular remodelling can reduce cardiovascular events, but the pathogenesis remains unclear. To clarify the role of BK channels in vascular remodelling, we use rats with BK channel α subunit knockout (BK α ‒/‒). The results show that BK α ‒/‒ rats have smaller inner and outer diameters, thickened aortic walls, increased fibrosis, and disordered elastic fibers of the aortas compared with WT rats. When the expression and function of BK α are inhibited in human umbilical arterial smooth muscle cells (HUASMCs), the expressions of matrix metalloproteinase 2 (MMP2), MMP9, and interleukin-6 are enhanced, while the expressions of smooth muscle cell contractile phenotype proteins are reduced. RNA sequencing, bioinformatics analysis and qPCR verification show that C1q/tumor necrosis factor-related protein 7 ( CTRP7) is the downstream target gene. Furthermore, except for that of MMPs, a similar pattern of IL-6, smooth muscle cell contractile phenotype proteins expression trend is observed after CTRP7 knockdown. Moreover, knockdown of both BK α and CTRP7 in HUASMCs activates PI3K/Akt signaling. Additionally, CTRP7 is expressed in vascular smooth muscle cells (VSMCs), and BK α deficiency activates the PI3K/Akt pathway by reducing CTRP7 level. Therefore, we first show that BK channel deficiency leads to vascular remodelling. The BK channel and CTRP7 may serve as potential targets for the treatment of cardiovascular diseases.

β1-adrenergic receptor (β1-AR), a member in the family of G-protein-coupled receptors, is a transmembrane receptor of great significance in the heart. Physiologically, catecholamines activate β1-AR to initiate a positive chronotropic, inotropic, and dromotropic change. It is believed that β1-AR couples to Gs protein and transmits the signal through second messenger cAMP. However, increasing research shows that β1-AR can also bind with Gi protein in addition to Gs. When β1-AR-Gi is biasedly activated, cardioprotective effects are introduced by the activated cGMP-protein kinase G (PKG) pathway and the transactivation of epidermal growth factor receptor (EGFR) pathway. The discovery of β1-AR-Gi signaling makes us reconsider the selectivity of G protein with regard to β1-AR, which also provides new ideas for the treatment of heart diseases. This review summarizes the discovery of β1-AR-Gi pathway, including the evidence that supports β1-AR’s capability to couple Gi, details of the transduction process and functions of the β1-AR-Gi signaling pathway.

Accumulating evidence suggests that liver injury can be induced by the over-expression of β1-adrenergic receptors (β1-ARs). High titers of autoantibodies specific to β1-adrenergic receptors (β1-AA) are detected in the sera of heart failure patients, potentially playing agonist-like roles. However, the role of β1-AA in liver function has not been characterized. In this study, we collect the sera of primary biliary cholangitis (PBC) patients, a condition which easily develops into liver fibrosis, and analyze the relationship between PBC and β1-AA. A passive immunization model is established to assess the effect of β1-AA on the liver. Subsequently, the effect of β1-AA on macrophages is investigated in vitro. Results show that PBC patients have a high titer and ratio of β1-AA, compared to controls. Liver injury and fibrosis are induced by β1-AA. In vitro experiments with ROS probe demonstrate that β1-AA induces macrophages to produce ROS and secrete TNFα. These effects can be partially reversed by metoprolol, a blocker for β1-AR. Results from the transwell and phagocytosis assays show that β1-AA promotes macrophage migration and phagocytosis. FCM tests suggest that β1-AA induces the alteration of M1 rather than M2 markers in macrophages. Finally, the Annexin V/PI assay indicates that macrophage culture supernatants stimulated by β1-AA cause hepatocyte apoptosis. Overall, these results suggest that β1-AA is involved in PBC. The β1-AA-induced activation, phagocytosis and phenotypic modification of macrophages may play an important role in the development of hepatic fibrosis and injury.