The oligosaccharides of Xiasangju alleviates dextran sulfate sodium-induced colitis in mice by inhibiting inflammation.

Xiasangju (XSJ) is a traditional Chinese herbal formula consisted of Prunella spica, Mulberry leaf and Chrysanthemi indici flos, which can be used to treat fever, headache and ulcer. To explore the effects of oligosaccharides from XSJ (OX) on colitis, we used dextran sulfate sodium (DSS) to establish colitis mouse models. After administration of OX with different doses on the control and colitis mice, we measured their body weights, disease activity indexes (DAI), lengths and histopathologic changes of colons, spleen indexes. The inflammatory cytokines and oxidative stress-related factors in serum, and the intestinal microbial community in feces were also detected. We found that colitis mice with oral administration of OX showed higher body weights and lower levels of DAI and spleen index. Tissue damages induced by DSS were also alleviated by OX treatment. The colitis mice with OX treatment exhibited lower levels of AST, ALT, BUN, CR, MDA and a down-regulated expression of IL-6 and IL-1ß, while the activity of SOD was up-regulated. Furthermore, OX improved the relative abundance of gut microbiota and restored the proportions of Bacteroidetes and Muribaculaceae. We found that oligosaccharides from XSJ alleviated the symptoms of colitis mice through its inhibitory effects on inflammation and oxidative stress, and also regulated the composition of intestinal flora, which indicates a beneficial role for patients with colitis.

The markers to delineate different phenotypes of macrophages related to metabolic disorders.

Macrophages have a wide variety of roles in physiological and pathological conditions, making them promising diagnostic and therapeutic targets in diseases, especially metabolic disorders, which have attracted considerable attention in recent years. Owing to their heterogeneity and polarization, the phenotypes and functions of macrophages related to metabolic disorders are diverse and complicated. In the past three decades, the rapid progress of macrophage research has benefited from the emergence of specific molecular markers to delineate different phenotypes of macrophages and elucidate their role in metabolic disorders. In this review, we analyze the functions and applications of commonly used and novel markers of macrophages related to metabolic disorders, facilitating the better use of these macrophage markers in metabolic disorder research.

CCAAT/Enhancer-Binding Proteins in Fibrosis: Complex Roles Beyond Conventional Understanding.

CCAAT/enhancer-binding proteins (C/EBPs) are a family of at least six identified transcription factors that contain a highly conserved basic leucine zipper domain and interact selectively with duplex DNA to regulate target gene expression. C/EBPs play important roles in various physiological processes, and their abnormal function can lead to various diseases. Recently, accumulating evidence has demonstrated that aberrant C/EBP expression or activity is closely associated with the onset and progression of fibrosis in several organs and tissues. During fibrosis, various C/EBPs can exert distinct functions in the same organ, while the same C/EBP can exert distinct functions in different organs. Modulating C/EBP expression or activity could regulate various molecular processes to alleviate fibrosis in multiple organs; therefore, novel C/EBPs-based therapeutic methods for treating fibrosis have attracted considerable attention. In this review, we will explore the features of C/EBPs and their critical functions in fibrosis in order to highlight new avenues for the development of novel therapies targeting C/EBPs.

FTZ Ameliorates Diabetic Cardiomyopathy by Inhibiting Inflammation and Cardiac Fibrosis in the Streptozotocin-Induced Model.

BACKGROUND: The pathogenesis and clinical features of diabetic cardiomyopathy (DCM) have been well studied in the past decade; however, effective approaches to prevent and treat this disease are limited. Fufang Zhenzhu Tiaozhi (FTZ) formula, a traditional Chinese prescription, is habitually used to treat dyslipidemia and diabetes. Recently, several studies have reported the therapeutic effects of FTZ on cardiovascular diseases. However, the effects of FTZ on DCM have not yet been fully elucidated. This study investigated the effects of FTZ on DCM and determined the mechanisms underlying its efficacy. METHODS: Diabetes was induced in mice by intraperitoneal injection of streptozotocin; the mice were randomly divided into a control group (Con), diabetes group (DCM), and diabetes-treated with FTZ (DCM + FTZ). Myocardial structural alterations, fibrosis biomarkers, and inflammation were observed. Besides, the potential targets and their related signaling pathways were analyzed using network pharmacology and further verified by Western blot. RESULTS: Diabetic mice showed significant body weight loss, hyperglycemia, and excessive collagen content in the cardiac tissue, while serum and myocardial inflammatory factors significantly increased. Nerveless, treatment with FTZ for 1 month significantly improved body weight, attenuated hyperglycemia, and alleviated diabetes-associated myocardial structure and function abnormalities. Furthermore, the serum levels of interleukin 12 (IL-12) and chemokine (C-C motif) ligand 2 (CCL2) as well as the mRNA levels of cardiac IL-12, IL-6, and C-C motif chemokine receptor 2 (Ccr2) reduced after FTZ treatment. Additionally, a total of 67 active compounds and 76 potential targets related to DCM were analyzed. Pathway and functional enrichment analyses showed that FTZ mainly regulates inflammation-related pathways, including MAPK and PI3K-AKT signaling pathways. Further investigation revealed that the activities of STAT3, AKT, and ERK were augmented in diabetic hearts but decreased in FTZ-treated cardiac tissues. CONCLUSION: Our results suggest that FTZ exhibits therapeutic properties against DCM by ameliorating hyperglycemia-induced inflammation and fibrosis via at least partial inhibition of AKT, ERK, and STAT3 signaling pathways.