Additional file 8: Table S8. of RNA sequencing from human neutrophils reveals distinct transcriptional differences associated with chronic inflammatory states

Differentially expressed long non-coding RNAs in different groups comparison. (XLSX 56 kb

Additional file 1: Table S1. of RNA sequencing from human neutrophils reveals distinct transcriptional differences associated with chronic inflammatory states

Genes identified as expressed in neutrophils in all 9 subjects. (XLSX 893 kb

Additional file 4: Figure S2. of Chromatin landscapes and genetic risk for juvenile idiopathic arthritis

Genes associated with these long-range interacting regions from CD4+ T cell ChIA-PET data. The genes associated with regions containing both H3K4me1 and H3K27ac marks have average higher FPKM than those genes that contained only H3K4me1 marks or those with no histone marks. (TIFF 17228 kb

Additional file 2: Figure S3. of Chromatin landscapes and genetic risk for juvenile idiopathic arthritis

Genome browser screen shots. Chromatin organization around the RUNX3 locus. (TIFF 10898 kb

Additional file 1: Table S1. of Chromatin landscapes and genetic risk in systemic lupus

is presenting genes (a) and functional pathways (b), as identified through Panther, associated with SNPs in systemic lupus. (DOCX 16 kb

DataSheet1_Ramulus mori (Sangzhi) alkaloids regulates gut microbiota disorder and its metabolism profiles in obese mice induced by a high-fat diet.PDF

The imbalance of gut microbiota has been confirmed to have a close pathological and physiological correlation with obesity and metabolic syndrome. Ramulus Mori (Sangzhi) Alkaloids (SZ-A) derived from twigs of mulberry was approved by the National Medical Products Administration of China in 2020 for the treatment of type 2 diabetes mellitus. In addition to its hypoglycemic effect, previous studies have confirmed that SZ-A also alleviates high-fat diet-induced obesity and non-alcoholic fatty liver disease and ameliorates obesity-linked adipose tissue metabolism and inflammation, indicating the potential of SZ-A to regulate obesity and metabolic syndrome. However, whether SZ-A can improve obesity and metabolic syndrome by regulating gut microbiota and its metabolism profiles remains unclear. The purpose of this study was to assess the effect of SZ-A on gut microbiota in obese mice and to explore the association among changes in gut microbiota, obesity, and lipid metabolism. The results showed that oral administration of SZ-A could significantly reduce body weight, fat mass, and the level of total cholesterol and low-density lipoprotein in serum in obese mice induced by a high-fat diet. Interestingly, SZ-A also regulated gut microbiota and changed the fecal metabolite composition of obese mice. Compared with the high-fat diet group, the ratio of Firmicutes to Bacteroides changed at the phylum level and the abundance of Bifidobacterium and Akkermansia muciniphila significantly increased at the genus level in the SZ-A group. The gut microbiota of the SZ-A group was reshaped and the relative abundance of microbial genes in bile acid metabolism and fatty acid metabolism were altered, which was consistent with the metabolomics results. Additionally, SZ-A greatly enriched the number of goblet cells and reduced inflammatory colon injury and pro-inflammatory macrophage infiltration induced by a high-fat diet in obese mice. In conclusion, SZ-A can alleviate obesity and metabolic syndrome by improving the gut microbiota and its metabolism profiles of obese mice induced by a high-fat diet.</p

Optimization of a Potent Class of Arylamide Colony-Stimulating Factor-1 Receptor Inhibitors Leading to Anti-inflammatory Clinical Candidate 4-Cyano-<i>N</i>-[2-(1-cyclohexen-1-yl)-4-[1-[(dimethylamino)acetyl]-4-piperidinyl]phenyl]-1<i>H</i>-imidazole-2-carboxamide (JNJ-28312141)

A class of potent inhibitors of colony-stimulating factor-1 receptor (CSF-1R or FMS), as exemplified by <b>8</b> and <b>21</b>, was optimized to improve pharmacokinetic and pharmacodynamic properties and potential toxicological liabilities. Early stage absorption, distribution, metabolism, and excretion assays were employed to ensure the incorporation of druglike properties resulting in the selection of several compounds with good activity in a pharmacodynamic screening assay in mice. Further investigation, utilizing the type II collagen-induced arthritis model in mice, culminated in the selection of anti-inflammatory development candidate JNJ-28312141 (<b>23</b>, FMS IC₅₀ = 0.69 nM, cell assay IC₅₀ = 2.6 nM). Compound <b>23</b> also demonstrated efficacy in rat adjuvant and streptococcal cell wall-induced models of arthritis and has entered phase I clinical trials