scholarly journals Multi-omics Analysis of the Biomarkers and Molecular Mechanism of Rheumatoid Arthritis With Bone Destruction

2021 ◽  
Author(s):  
Qian Huang ◽  
Jiang Su ◽  
Weihua Zhang ◽  
Shengjia Chang ◽  
Silin Li ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
16S Rrna ◽  
Bone Destruction ◽  
Gut Bacteria ◽  
Plasma Metabolites ◽  
Healthy Control ◽  
Novel Biomarkers ◽  
Bacteria And Fungi ◽  
And Function

Abstract ObjectivesOur study aimed to elucidate the role of metabolites, bacteria, and fungi in rheumatoid arthritis (RA) patients with bone destruction (BD(+)) and find some biomarkers to predicate bone progression of RA.MethodsWe conducted plasma metabolites of the 127 RA patients and 69 healthy control by using nontargeted liquid chromatography-mass spectrometry (LC-MS), and the gut bacteria and fungi were assessed by 16S rRNA and internal transcribed spacer (ITS).ResultsCompared with RA patients without bone destruction (BD(-)), some metabolites, bacteria, and fungi altered in BD(+). Sever metabolites were selected as key metabolites for classifying the BD(+) and BD(-) groups with moderate accuracy (AUC=0.71). Metabolites-groups, metabolites-metabolites, and metabolites-clinical factors had a certain correlation, and 7 metabolites were enriched in glycerophospholipid metabolism and L-arginine and proline metabolism pathways. The bacteria and fungi of the BD(+) group showed significant differences in composition and function compared with BD(-) group. The changed 4 bacteria and 12 fungi yielded accuracy (AUC=0.74 and AUC=0.87, respectively) for the two groups. Taken 7 metabolites, 4 bacteria and 12 fungi as a panel for AUC analysis, an improved AUC of 0.99 significantly discriminated the two groups. The changed metabolites, gut bacteria, and fungi may affected the pathway related to L-arginine.ConclusionsOur nontargeted LC-MS, 16S rRNA, and ITS highlight a novel link among the metabolites, bacteria, fungi, and pathology of BD(+), which contributed to our understanding of the role of metabolites, bacteria, and fungi in BD(+) aetiology and offers some novel biomarkers to predict the bone progression of RA.

scholarly journals Pharmacokinetics-Based Chronoefficacy of Semen Strychni and Tripterygium Glycoside Tablet Against Rheumatoid Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingpan Lin ◽  
Lu Gao ◽  
Yanke Lin ◽  
Shuai Wang ◽  
Zemin Yang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Destruction ◽  
Systemic Exposure ◽  
Inflammatory Factors ◽  
Systemic Autoimmune Disease ◽  
Active Ingredients ◽  
Tnf Α ◽  
Exposure Levels ◽  
Semen Strychni

Rheumatoid arthritis is a systemic autoimmune disease characterized by synovial inflammation and bone destruction. Identifying drugs with time-varying efficacy and toxicity, and elucidating the mechanisms would help to improve treatment efficacy and reduce adverse effects. Here, we aimed to determine the chronoefficacy of semen strychni (SS) and tripterygium glycoside tablet (TGT) against rheumatoid arthritis in mice, and to investigate a potential role of circadian pharmacokinetics in generating chronoefficacy. SS extract and TGT suspension were prepared with ultrasonication. Effects of SS and TGT on collagen-induced arthritis (CIA) were evaluated by measuring TNF-α and IL-6 levels. SS dosed at ZT18 was more effective in protecting against CIA than drug dosed at ZT6 (i.e., lower levels of key inflammatory factors at ZT18 than at ZT6). This was accompanied by higher systemic exposure levels of strychnine and brucine (two main putative active ingredients of SS) in ZT18-treated than in ZT6-treated CIA mice. TGT dosing at ZT2 showed a better efficacy against CIA as compared to herb doing at ZT14. Consistently, ZT2 dosing generated a higher exposure of triptolide (a main putative active ingredient of TGT) as compared to ZT14 dosing in CIA mice. Moreover, strychnine, brucine, and triptolide significantly inhibited the proliferation of fibroblast-like synoviocytes, and reduced the production of TNF-α and IL-6 and the mRNAs of TNF-α, IL-6, COX-2, and iNOS, suggesting that they possessed an anti-arthritis activity. In conclusion, SS and TGT display chronoefficacy against rheumatoid arthritis in mice, that is attributed to circadian pharmacokinetics of main active ingredients. Our findings have implications for improving treatment outcomes of SS and TGT via timed delivery.

scholarly journals Pathogenesis and Function of Interleukin-35 in Rheumatoid Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Pan Lin Xin ◽  
Li Fan Jie ◽  
Qian Cheng ◽  
Du Yi Bin ◽  
Cheng Wen Dan
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Cell ◽  
T Regulatory Cells ◽  
Therapeutic Potential ◽  
Bone Destruction ◽  
Pathological Process ◽  
Interleukin 12 ◽  
Synovial Hyperplasia ◽  
And Function ◽  
Anti Inflammatory Cytokine

It is well known that RA (Rheumatoid arthritis) is an autoimmune disease characterized by multiple and symmetric arthropathy. The main pathological features of RA are synovial hyperplasia, angiogenesis, pannus formation, inflammatory cell infiltration, articular cartilage, bone destruction, and ultimately joint dysfunction, even deformity. IL-35 (Interleukin-35) is a new member of the IL-12 (Interleukin-12) family, which is an immunosuppressive and anti-inflammatory cytokine secreted mainly by Treg (T regulatory cells). There is evidence suggested that IL-35 can attenuate the progression of RA through influencing the immune and pathological process. It suggests that IL-35 played an important role in the pathogenesis of RA, and can be used as a potential target for the future treatment of RA. This review summarizes the recent advances of IL-35 in the pathological roles and the therapeutic potential roles in RA.

scholarly journals Bacterial Diversity and Community in Regional Water Microbiota between Different Towns in World’s Longevity Township Jiaoling, China

Diversity ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 361
Author(s):  
Lei Wu ◽  
Xinqiang Xie ◽  
Jumei Zhang ◽  
Yu Ding ◽  
Qingping Wu
Keyword(s):  
16S Rrna ◽  
High Throughput Sequencing ◽  
The Other ◽  
Rrna Gene ◽  
Metabolic Characteristics ◽  
Kegg Pathways ◽  
Healthy Longevity ◽  
And Function ◽  
Regional Water

Healthy longevity is associated with many factors, however, the potential correlation between longevity and microbiota remains elusive. To address this, we explored environmental microbiota from one of the world’s longevity townships in China. We used 16S rRNA gene high-throughput sequencing to analyze the composition and function of water microbiota. The composition and diversity of water microbiota significantly differed between the towns. Lactobacillus, Streptococcus, Bacteroides, Faecalibacterium, and Stenotrophomonas were only dominant in Xinpu, a town with an exceptionally high centenarian population. Several biomarkers were identified, including Flavobacterium, Acinetobacter, Paracoccus, Lactobacillales, Psychrobacter, Bacteroides, Ruminococcaceae, and Faecalibacterium, and these shown to be responsible for the significant differences between towns. The main species contributing to the differences between towns were Cyanobacteria, Cupriavidus and Ralstonia. Based on KEGG pathways showed that the predicted metabolic characteristics of the water microbiota in Xinpu towns were significantly different to those of the other towns. The results revealed significant differences in the composition and diversity of water microbiota in the longevity township. These findings provide a foundation for further research on the role of water microbiota in healthy longevity.

Post Translational Modification and its pathologic association in Rheumatoid Arthritis: A brief perspective

2021 ◽  
Vol 22 ◽  
Author(s):  
Vishnupreetha Vasudevan ◽  
Prachi Agnihotri ◽  
Sagarika Biswas
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Pain ◽  
Cyclic Peptide ◽  
Delayed Diagnosis ◽  
Living System ◽  
The Body ◽  
Post Translational Modification ◽  
And Function ◽  
Inflammatory Autoimmune Disease

: Post Translational Modification (PTM) is the process in which covalent addition of functional groups on protein happens to maintain their structure, function and stability. Every PTM process in our living system happens to increase the functional diversity of protein. But sometimes it happens without any regulation and occurrence of this specific change in proteins are leading to autoimmunity. Rheumatoid arthritis (RA) is one such chronic, inflammatory, autoimmune disease that affects joints. Proper treatment can be manageable for RA, but it is not completely curable. Delayed diagnosis of RA can cause severe bone pain, stiffness, inflammation, redness in joints and affect other parts of the body such as liver, kidney etc. Early diagnosis of disease is preferable to cure it effectively. Currently, Rheumatoid factor (RF) and anti-citrullinated cyclic peptide (Anti-CCP) are considered as biomarkers to diagnose RA. Other than citrullination several other PTM’s are also involved in generation of autoantibodies such as, carbamylation, glycosylation, glycation, acetylation, ubiquitination, proteolysis, phosphorylation, lipidation. Aim of this review is to elucidate several considerable changes in form, nature and function of above PTMs in RA, affecting joints and day to day life. This review will give a recent overview on the role of PTMs in the pathogenesis of RA, focusing on the modifications.

The impact of epigenetics on cardiovascular disease

2020 ◽  
Vol 98 (1) ◽  
pp. 12-22 ◽  
Author(s):  
Dimple Prasher ◽  
Steven C. Greenway ◽  
Raja B. Singh
Keyword(s):  
Cardiac Fibrosis ◽  
Mortality And Morbidity ◽  
Rna Molecules ◽  
Expression Of Genes ◽  
Non Coding Rna ◽  
Novel Biomarkers ◽  
External Risk ◽  
And Function ◽  
The Impact

Mortality and morbidity from cardiovascular diseases (CVDs) represents a huge burden to society. It is recognized that environmental factors and individual lifestyles play important roles in disease susceptibility, but the link between these external risk factors and our genetics has been unclear. However, the discovery of sequence-independent heritable DNA changes (epigenetics) have helped us to explain the link between genes and the environment. Multiple diverse epigenetic processes, including DNA methylation, histone modification, and the expression of non-coding RNA molecules affect the expression of genes that produce important changes in cellular differentiation and function, influencing the health and adaptability of the organism. CVDs such as congenital heart disease, cardiomyopathy, heart failure, cardiac fibrosis, hypertension, and atherosclerosis are now being viewed as much more complex and dynamic disorders. The role of epigenetics in these and other CVDs is currently under intense scrutiny, and we can expect important insights to emerge, including novel biomarkers and new approaches to enable precision medicine. This review summarizes the recent advances in our understanding of the role of epigenetics in CVD.

scholarly journals Bile Acids and Microbiota: Multifaceted and Versatile Regulators of the Liver–Gut Axis

2021 ◽  
Vol 22 (3) ◽  
pp. 1397
Author(s):  
Niklas Grüner ◽  
Jochen Mattner
Keyword(s):  
Bile Acids ◽  
Current Knowledge ◽  
Gut Bacteria ◽  
Intestinal Lumen ◽  
Clostridioides Difficile ◽  
Physiological Processes ◽  
Local Site ◽  
Inflammatory Bowel ◽  
And Function

After their synthesis from cholesterol in hepatic tissues, bile acids (BAs) are secreted into the intestinal lumen. Most BAs are subsequently re-absorbed in the terminal ileum and are transported back for recycling to the liver. Some of them, however, reach the colon and change their physicochemical properties upon modification by gut bacteria, and vice versa, BAs also shape the composition and function of the intestinal microbiota. This mutual interplay of both BAs and gut microbiota regulates many physiological processes, including the lipid, carbohydrate and energy metabolism of the host. Emerging evidence also implies an important role of this enterohepatic BA circuit in shaping mucosal colonization resistance as well as local and distant immune responses, tissue physiology and carcinogenesis. Subsequently, disrupted interactions of gut bacteria and BAs are associated with many disorders as diverse as Clostridioides difficile or Salmonella Typhimurium infection, inflammatory bowel disease, type 1 diabetes, asthma, metabolic syndrome, obesity, Parkinson’s disease, schizophrenia and epilepsy. As we cannot address all of these interesting underlying pathophysiologic mechanisms here, we summarize the current knowledge about the physiologic and pathogenic interplay of local site microbiota and the enterohepatic BA metabolism using a few selected examples of liver and gut diseases.

scholarly journals The role of adhesion molecules in bone destruction in rheumatoid arthritis mediated by osteoblastsosteoclasts interaction.

Ensho ◽  
1994 ◽  
Vol 14 (6) ◽  
pp. 467-472
Author(s):  
Masao Shingu ◽  
Michi Hashimoto ◽  
Tetsurou Isayama ◽  
Yasuko Koshihara ◽  
Tatehumi Kuroki ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adhesion Molecules ◽  
Bone Destruction

TLRs Play Crucial Roles in Regulating RA Synoviocyte

2020 ◽  
Vol 20 (8) ◽  
pp. 1156-1165 ◽  
Author(s):  
Xuling Luo ◽  
Juncheng Cui ◽  
Xin Long ◽  
Zhiwei Chen
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Inflammatory Disease ◽  
Chinese Herb ◽  
Bone Destruction ◽  
Inflammatory Factors ◽  
Exact Role ◽  
Autoimmune Inflammatory Disease ◽  
Fibroblast Like Synoviocytes

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease comparing the inflammation of synovium. Macrophage-like synoviocytes and fibroblast-like synoviocytes (synoviocytes) are crucial ingredients of synovium. Therein, a lot of research has focused on synoviocytes. Researches demonstrated that TLR1, TLR2, TLR3, TLR4, TLR5, TLR6 TLR7 and TLR9 are expressed in synoviocyte. Additionally, the expression of TLR2, TLR3, TLR4 and TLR5 is increased in RA synoviocyte. In this paper, we review the exact role of TLR2, TLR3, TLR4 and TLR5 participate in regulating the production of inflammatory factors in RA synoviocyte. Furthermore, we discuss the role of vasoactive intestinal peptide (VIP), MicroRNA, Monome of Chinese herb and other cells (Monocyte and T cell) influence the function of synoviocyte by regulating TLRs. The activation of toll-like receptors (TLRs) in synoviocyte leads to the aggravation of arthritis, comparing with angiogenesis and bone destruction. Above all, TLRs are promising targets for managing RA.

scholarly journals Posttranscriptional Modifications in 16S and 23S rRNAs of the Archaeal Hyperthermophile Sulfolobus solfataricus

1998 ◽  
Vol 180 (11) ◽  
pp. 2883-2888 ◽  
Author(s):  
Kathleen R. Noon ◽  
Eveline Bruenger ◽  
James A. McCloskey
Keyword(s):  
16S Rrna ◽  
Potential Role ◽  
Thermal Environment ◽  
Sulfolobus Solfataricus ◽  
Structure And Function ◽  
Modified Nucleosides ◽  
23S Rrna ◽  
And Function ◽  
Polynucleotide Chain

ABSTRACT Posttranscriptional modification is common to many types of RNA, but the majority of information concerning structure and function of modification is derived principally from tRNA. By contrast, less is known about modification in rRNA in spite of accumulating evidence for its direct participation in translation. The structural identities and approximate molar levels of modifications have been established for 16S and 23S rRNAs of the archaeal hyperthermophile Sulfolobus solfactaricus by using combined chromatography-mass spectrometry-based methods. Modification levels are exceptionally high for prokaryotic organisms, with approximately 38 modified sites in 16S rRNA and 50 in 23S rRNA for cells cultured at 75°C, compared with 11 and 23 sites, respectively, in Escherichia coli. We structurally characterized 10 different modified nucleosides in 16S rRNA, 64% (24 residues) of which are methylated at O-2′ of ribose, and 8 modified species in 23S rRNA, 86% (43 residues) of which are ribose methylated, a form of modification shown in earlier studies to enhance stability of the polynucleotide chain. From cultures grown at progressively higher temperatures, 60, 75, and 83°C, a slight trend toward increased ribose methylation levels was observed, with greatest net changes over the 23°C range shown for 2′-O-methyladenosine in 16S rRNA (21% increase) and for 2′-O-methylcytidine (24%) and 2′-O-methylguanosine (22%) in 23S rRNA. These findings are discussed in terms of the potential role of modification in stabilization of rRNA in the thermal environment.

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