fecal-microbiota-transplantation-detection-prevalence-iga-coated

Fecal Microbiota Transplantation and Detection of Prevalence of IgA-Coated Bacteria in the Gut

Gut microbiota exert pleiotropic roles in human health and disease. Fecal microbiota transplantation (FMT) is an effective method to investigate the ...

Sichuan University

This study aims to discuss risk factors associated with cervical spine involvement (CSI) in patients with rheumatoid arthritis (RA).

Cervical spine involvement risk factors in rheumatoid arthritis: a meta-analysis.

The aim of the present study was to investigate the influence of a high-fat diet (HFD) on hematopoietic system recovery under stress condition caused by 5-fluorouracil (5-Fu) and to evaluate the alleviating benefit of proliferator-activated receptor γ (PPAR-γ) inhibition on aggravation of 5-Fu-induced toxicity under HFD. Survival rates of HFD or normal diet (ND) mice were monitored after 5-Fu injection. Hematopoietic stem cells (HSCs) and the progenitor cells in bone marrow were detected at various time points after 5-Fu administration by flow cytometry. Genes expressed in stem cell and platelet proliferation was tested by reverse transcription polymerase chain reaction. The blood cell profile and coagulation function were determined with an ADVIA 120 hematology system and rotational thromboelastometry, respectively. None of HFD mice remained alive after 5-Fu injection, whereas 87.4% of ND mice survived. HFD accelerated 5-Fu-induced myelosuppression and cytopenia in the circulation, reflected by the worse recovery of HSCs and myeloid progenitor cells. In HFD mice, the number of platelets significantly decreased, and the Vcam-1/Vla-4 signal pathway was downregulated in bone marrow. Meanwhile, mice receiving HFD exhibited dysfunction of blood coagulation with increased clotting formation time. However, pretreatment of HFD mice with bisphenol A diglycidyl ether (BADGE), the PPAR-γ antagonist, reversed the acute lethal toxicity and bone marrow suppression of 5-Fu and accelerated the recovery of HSCs and platelets. In the light of these results, HFD could exacerbate 5-Fu-induced bone marrow toxicity and cytopenia. BADGE treatment offers a potential strategy to alleviate the aggravated hematopoiesis under an HFD.

High fat diet-induced obesity exacerbates hematopoiesis deficiency and cytopenia caused by 5-fluorouracil via peroxisome proliferator-activated receptor γ.

The anti-inflammatory effect of abatacept is most pronounced in patients with high-titer autoantibodies (including anticitrullinated protein antibodies [ACPA] and rheumatoid factor [RF]). Considering that autoantibodies trigger inflammatory cytokine production by monocytes and that abatacept binds to monocytes, influencing their functional state, we hypothesized that abatacept may effectively inhibit the production of several different cytokines by ACPA- or RF-challenged monocytes.

Abatacept blocks anti-citrullinated protein antibody and rheumatoid factor mediated cytokine production in human macrophages in IDO-dependent manner.

Behçet disease (BD) is a recurrent vasculitis characterized by oral and genital mucous membrane ulcers, uveitis, and skin lesions but only rarely leg ulcers. To our knowledge, no efficacious therapy has been described for BD patients with complicating, destructive leg ulcers.

Successful mesenchymal stem cell treatment of leg ulcers complicated by Behcet disease: A case report and literature review.

Acute respiratory distress syndrome threatens public health with high morbidity and mortality due to ineffective intervention whereby lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice provides a research model. The seeds of Euphorbia lathyris L. have a long history of usage in Traditional Chinese Medicine. Euphorbia factors L1-L11, extracted from this herb, have been reported to have anti-inflammation and anti-cancer effects. Here, we report the preventive and therapeutic potential of Euphorbia factor L2 (EFL2) on LPS-induced ALI in mice, where EFL2 attenuated pathological alterations in the lung and improved survival. Significant suppression of the recruitment and transmigration of inflammatory cells, specifically neutrophils, by 40 mg/kg of EFL2 was observed. EFL2 exerted potent anti-inflammatory effects by decreasing the levels of interleukin-1β (IL-1 β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF- α), interleukin-8 (IL-8) and myeloperoxidase (MPO) in the lung and bronchioalveolar lavage fluid. Consistent with the findings in vivo, EFL2 also showed robust inhibitory effects on the production of IL-1 β, IL-6, TNF- α and IL-8 released from LPS-stimulated RAW264.7 cells in vitro. Interestingly, this effect appeared to be mediated by EFL2's inhibition of NF-κB signaling activation, but not the MAPK pathway. Not only phosphorylation of IKK α/β and IκBα was down-regulated, p65 translocation and its DNA-binding activity were also significantly suppressed by EFL2. Moreover, overexpression of p65 reversed the inhibitory effect of EFL2 in LPS-induced NF-κB activation and cytokines production. The observed anti-inflammatory bioactivity of EFL2 indicates its potential as a drug development candidate, particularly for LPS-mediated disorders of inflammation.

Euphorbia factor L2 alleviates lipopolysaccharide-induced acute lung injury and inflammation in mice through the suppression of NF-κB activation.

Inflammatory responses require mobilization of innate immune cells from the bone marrow. The functionality of this process depends on the state of the bone marrow microenvironment. We therefore hypothesized that molecular changes in osteoblasts, which are essential stromal cells of the bone marrow microenvironment, influence the inflammatory response. Here, we show that osteoblast-specific expression of the AP-1 transcription factor Fra-2 (Fra-2) induced a systemic inflammatory state with infiltration of neutrophils and proinflammatory macrophages into the spleen and liver as well as increased levels of proinflammatory cytokines, such as interleukin-1β (IL-1β), IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF). By  inhibition of osteopontin (OPN) in Fra-2 mice, we demonstrated that this process was dependent on OPN expression, which mediates alterations of the bone marrow niche. OPN expression was transcriptionally enhanced by Fra-2 and stimulated mesenchymal stem cell (MSC) expansion. Furthermore, in a murine lung injury model, Fra-2 mice showed increased inflammatory responses and more severe disease features via an enhanced and sustained inflammatory response to lipopolysaccharide (LPS). Our findings demonstrate for the first time that molecular changes in osteoblasts influence the susceptibility to inflammation by altering evasion of innate immune cells from the bone marrow space.

Fra-2 Expression in Osteoblasts Regulates Systemic Inflammation and Lung Injury through Osteopontin.

Oral microbial dysbiosis is known to increase susceptibility of an individual to develop rheumatoid arthritis (RA). Individuals at-risk of RA may undergo different phases of disease progression. In this study, we aim to investigate whether and whereby the oral microbiome communities alter prior to symptoms of RA. Seventy-nine saliva samples were collected from 29 high-risk individuals, who were positive for anti-citrullinated protein antibodies (ACPA) and have no clinical arthritis, 27 RA patients and 23 healthy controls (HCs). The salivary microbiome was examined using 16S ribosomal RNA gene sequencing. Alpha and beta diversity analysis and the linear discriminant analysis were applied to examine the bacterial diversity, community structure and discriminatory taxa between three groups, respectively. The correlation between salivary bacteria and autoantibodies were analyzed. In the "pre-clinical" stages, salivary microbial diversity was significantly reduced comparing to RA patients and HCs. In contrast to HCs, like RA patients, individuals at high-risk for RA showed a reduction in the abundance of genus  and the species , but an expansion of _6. Unexpectedly, the relative abundance of , reported as opportunistic pathogens for RA development, was significantly decreased in high-risk individuals. Additionally, we identified four genera in the saliva from high-risk individuals positively correlated with serum ACPA titers, and the other two genera inversely displayed. In summary, we observed a characteristic compositional change of salivary microbes in individuals at high-risk for RA, suggesting that oral microbiota dysbiosis occurs in the "pre-clinical" stage of RA and are correlated with systemic autoimmune features.

Oral Microbiota Perturbations Are Linked to High Risk for Rheumatoid Arthritis.

C-reactive protein (CRP) is often normal in patients with psoriatic disease. Herein, we aimed to define markers of systemic inflammation in patients with monomorphic and polymorphic psoriatic skin, entheseal, and joint disease.

A set of serum markers detecting systemic inflammation in psoriatic skin, entheseal, and joint disease in the absence of C-reactive protein and its link to clinical disease manifestations.

Sirtuins (SIRTs) are NAD-dependent lysine deacylases, regulating many important biological processes such as metabolism and stress responses. SIRT inhibitors may provide potential benefits against SIRT-driven human diseases. Development of efficient assay platforms based on fluorogenic substrates will facilitate the discovery of high-quality SIRT inhibitors. We here report 16 new fluorogenic peptide substrates (P1-P16) designed with structurally diverse tetrapeptides and acyl modifications. Tests of P1-P16 against SIRT isoforms identified several sensitive substrates for SIRT1, SIRT2, SIRT3 and SIRT5, which manifested lower K values and higher catalytic efficiency, and particularly had less signal interference in inhibitor screening compared with our previously reported internally quenched fluorescent substrates. Co-crystallization of sensitive substrates P13 and P15 with SIRT5 revealed an unexpected binding mode, involving interactions with residues from active site bordering surfaces, different from that observed for other peptides derived from natural protein substrates. By using SIRT5 sensitive substrates, we found that TW-37, a Bcl-2 inhibitor, displayed low micromolar inhibition to SIRT5, which was further validated by isothermal titration calorimetry analyses, offering a new point to develop dual-action SIRT5/Bcl-2 inhibitors against cancers. This work provides assay platform and structural basis for developing new substrates and inhibitors targeting human SIRTs.

Sensitive fluorogenic substrates for sirtuin deacylase inhibitor discovery.

As a gigantic community in the human body, the microbiota exerts pleiotropic roles in human health and disease ranging from digestion and absorption of nutrients from food, defense against infection of pathogens, to regulation of immune system development and immune homeostasis. Recent advances in "omics" studies and bioinformatics analyses have broadened our insights of the microbiota composition of the inner and other surfaces of the body and their interactions with the host. Apart from the direct contact of microbes at the mucosal barrier, metabolites produced or metabolized by the gut microbes can serve as important immune regulators or initiators in a wide variety of diseases, including gastrointestinal diseases, metabolic disorders and systemic rheumatic diseases. This review focuses on the most recent understanding of how the microbiota and metabolites shape rheumatic diseases. Studies that explore the mechanistic interplay between microbes, metabolites and the host could thereby provide clues for novel methods in the diagnosis, therapy, and prevention of rheumatic diseases.

Article	Year
Cervical spine involvement risk factors in rheumatoid arthritis: a meta-analysis. International journal of rheumatic diseases\| PubMed ID: 28524646	2017
High fat diet-induced obesity exacerbates hematopoiesis deficiency and cytopenia caused by 5-fluorouracil via peroxisome proliferator-activated receptor γ. Experimental hematology\| PubMed ID: 29305999	2018
Abatacept blocks anti-citrullinated protein antibody and rheumatoid factor mediated cytokine production in human macrophages in IDO-dependent manner. Arthritis research & therapy\| PubMed ID: 29415763	2018
Successful mesenchymal stem cell treatment of leg ulcers complicated by Behcet disease: A case report and literature review. Medicine\| PubMed ID: 29668637	2018
Euphorbia factor L2 alleviates lipopolysaccharide-induced acute lung injury and inflammation in mice through the suppression of NF-κB activation. Biochemical pharmacology\| PubMed ID: 30055150	2018
Fra-2 Expression in Osteoblasts Regulates Systemic Inflammation and Lung Injury through Osteopontin. Molecular and cellular biology\| PubMed ID: 30181393	2018
Oral Microbiota Perturbations Are Linked to High Risk for Rheumatoid Arthritis. Frontiers in cellular and infection microbiology\| PubMed ID: 32039051	2019
A set of serum markers detecting systemic inflammation in psoriatic skin, entheseal, and joint disease in the absence of C-reactive protein and its link to clinical disease manifestations. Arthritis research & therapy\| PubMed ID: 32051028	2020
Sensitive fluorogenic substrates for sirtuin deacylase inhibitor discovery. European journal of medicinal chemistry\| PubMed ID: 32163813	2020
Microbiota and metabolites in rheumatic diseases. Autoimmunity reviews\| PubMed ID: 32240855	2020

Yubin Luo

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