Postbiotics in rheumatoid arthritis: emerging mechanisms and intervention perspectives.

Rheumatoid arthritis (RA) is a prevalent chronic autoimmune disease that affects individuals of all age groups. Recently, the association between RA and the gut microbiome has led to the investigation of postbiotics as potential therapeutic strategies. Postbiotics refer to inactivated microbial cells, cellular components, or their metabolites that are specifically intended for the microbiota. Postbiotics not only profoundly influence the occurrence and development of RA, but they also mediate various inflammatory pathways, immune processes, and bone metabolism. Although they offer a variety of mechanisms and may even be superior to more conventional "biotics" such as probiotics and prebiotics, research on their efficacy and clinical significance in RA with disruptions to the intestinal microbiota remains limited. In this review, we provide an overview of the concept of postbiotics and summarize the current knowledge regarding postbiotics and their potential use in RA therapy. Postbiotics show potential as a viable adjunctive therapy option for RA.

Difficult-to-treat rheumatoid arthritis treated with Abatacept combined with Baricitinib: A case report.

BACKGROUND: Sporadic cases of rheumatoid arthritis (RA) due to unsatisfactory responses to Abatacept (ABT) have been reported; however, the rescue therapy has not been finalized. Here, we present a case with difficult-to-treat RA (D2T RA) that was resistant to either a single ABT or a Janus kinase (JAK) inhibitor (Tofacitinib), but improved with a combination of ABT and JAK inhibitor (Baricitinib, BAT). CASE SUMMARY: A 46-year-old Chinese woman who had RA for ten years that was resistant to Tocilizumab, Etanercept, Adalimumab, and ABT. According to the European League Against Rheumatism definition, the patient was diagnosed with D2T RA. It was then improved with a combination of ABT and a JAK inhibitor BAT. CONCLUSION: ABT combined with BAT may be an acceptable strategy for treating D2T RA.

The effects of iguratimod combined with methotrexate and hydroxychloroquine on bone mineral density in patients with rheumatoid arthritis.

In this study, we aimed to explore the effects of iguratimod (IGU) combined with methotrexate (MTX) and hydroxychloroquine (HCQ) on bone mineral density (BMD) in patients with rheumatoid arthritis (RA). 76 patients who received IGU combined with MTX and HCQ were included in this retrospective study. After 48 weeks treatment of IGU combined with MTX and HCQ, the BMD at the L1-L4 (p <0.01), left femoral neck (p <0.01) and left total hip (p <0.01) were significantly increased. Especially, the BMD at left femoral neck was significantly increased from baseline to week 24 (p <0.05). With regard to inflammatory reaction, there were statistically significant reductions in the RF (p <0.05), CRP (p <0.05), ESR (p <0.01), anti-CCP (p <0.01) from baseline to week 48. The most common adverse events were gastrointestinal reaction and transaminase elevation. The combination of IGU, MTX and HCQ could significantly improve the BMD and restrain inflammatory reaction. No additional adverse events were noticed in our research. This study provides valuable information for treatment of osteopenia in patients with RA.

Iridin Prevented Against Lipopolysaccharide-Induced Inflammatory Responses of Macrophages via Inactivation of PKM2-Mediated Glycolytic Pathways.

PURPOSE: Abnormal glycolysis of immune cells contributed to the development of inflammatory response. Inhibition of this Warburg phenotype could be a promising strategy for preventing various inflammatory diseases. Iridin (IRD) is a natural isoflavone, and exerts anticancer, antioxidant, and anti-inflammatory effects. However, the underlying mechanism of IRD on acute inflammation remains unknown. In this study, the protective effects of IRD against lipopolysaccharide (LPS)-induced inflammation were investigated in murine macrophage RAW264.7 cells and in mice. METHODS: The inhibition of IRD on NO production in culture medium was detected by Griess assay while the levels of TNF-α, IL-1ß, and MCP-1 were detected by ELISA assay. The effects of IRD on OCR and ECAR levels in LPS-treated macrophages were monitored by using Seahorse Analyzer. The apoptosis rate as well as the release of ROS and NO of RAW264.7 cells were analyzed by flow cytometric assay. The protective effects of IRD were investigated on LPS-induced inflammation in mice. The expressions of PKM2 and its downstream (p-JAK1, p-STAT1, p-STAT3, p-p65, iNOS, and COX2) in cells and in lung tissues were detected by Western blotting analysis. RESULTS: IRD treatment at the concentrations of 12.5-50 µM significantly inhibited the productions of TNF-α, IL-1ß, MCP-1, and ROS, and suppressed the levels of glucose uptake and lactic acid in LPS-treated RAW264.7 cells. Oral administration with IRD (20-80 mg/kg) inhibited LPS-induced acute lung injury as well as inflammatory cytokine production in mice. Moreover, IRD targeted pyruvate kinase isozyme type M2 (PKM2) and suppressed its downstream p-JAK1, p-STAT1, p-STAT3, p-p65, iNOS, and COX2, which could be abolished by PKM2 agonist DASA-58 and antioxidant N-acetyl-L-cysteine, but partly be reversed by NF-κB activator CUT129 and JAK1 activator RO8191. CONCLUSION: IRD alleviated LPS-induced inflammation through suppressing PKM2-mediated pathways, and could be a potential candidate for the prevention of inflammatory diseases.

Isofraxidin ameliorated influenza viral inflammation in rodents via inhibiting platelet aggregation.

Platelets have been proved to exacerbate influenza infection and its complications. Inhibition of platelet activation may be a feasible method for preventing severe infection and secondary acute lung injury (ALI). Isofraxidin (IFD) is a natural coumarin isolated from the plants Sarcandra glabra and Siberian ginseng, and exerts anticancer, antioxidant and antiinflammatory effects. In the present study, we examined the therapeutic effects of IFD in ADP- or arachidonic acid (AA)-induced platelet aggregation model and in influenza A virus (IAV)-induced ALI mouse model. The results showed that IFD significantly inhibited platelet aggregation induced by ADP and AA in vitro in a concentration-dependent manner as well as the release of soluble P-selectin and platelet factor 4. Moreover, IFD significantly relieved IAV-induced lung inflammation, reduced the expressions of platelet activation biomarkers (P-selectin and CD61), decreased the serum levels of TNF-α, IL-1ß, IL-6 and MIP-2, suppressed peripheral platelet aggregation and prolonged the survival time of infected mice. The western blotting results also demonstrated that IFD reduced the phosphorylation levels of PI3K, AKT and p38 in the activated platelets stimulated by ADP and IAV infection. But IFD did not have any effects on IAV replication. It indicated that IFD ameliorated IAV-induced severe lung damage and lethal infection by suppressing platelet aggregation via regulating PI3K/AKT and MAPK pathways.

Acute diffuse alveolar haemorrhage accompanied by gastrointestinal bleeding in a patient with serious systemic lupus erythematosus: A case report.

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects many organs, but multisystem dysfunction is rare. Here, we report a case of a 29-year-old woman who was initially diagnosed with SLE complications including lupus nephritis, lupus encephalopathy, renal hypertension, thrombocytopenia, anaemia and hyperkalaemia. She recovered following treatment with high dose methylprednisolone, intravenous immunoglobulin (IVIG) and continuous renal replacement therapy (CRRT). However, a few days after hospital discharge, she developed gastrointestinal bleeding. Although intensive treatment was administered, the patient deteriorated rapidly and had a progressive decline in oxygen saturation followed by diffuse alveolar haemorrhage and acute left heart failure. Inotropic therapy, mechanical ventilation, blood transfusion, CRRT, antibiotics, intravenous glucocorticoids and other support therapies were initiated and gradually the patient's vital signs stabilized and haemoptysis subsided. This case report emphasises that complications of SLE can occur at any stage of the disease, especially in patients with active SLE. Therefore, it is important for clinicians to be aware of the rare presentations of SLE and its complex management. For multisystem dysfunction, early intensive treatment with high dose corticosteroids and cyclophosphamide is advocated.

The clinical significance of HRCT in evaluation of patients with rheumatoid arthritis-associated interstitial lung disease: a report from China.

The objective of this study is to describe the interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients of China, and to study clinical significance of high-resolution computed tomography (HRCT) in evaluation and treatment. One hundred and ten Chinese patients (79 women and 31 man) diagnosed with RA between December 2008 to November 2009 were analyzed. According to the HRCT, 47 (42.73%) RA patients were diagnosed as ILD. Old age, smoking and pulmonary rales were closely related to ILD (P < 0.05). The main appearances of ILD were ground-glass (39.09%), honeycombing (4.55%), reticular patterns and consolidation (1.82%). Patients with reticular patterns and honeycombing were more likely to show the respiratory symptoms. It was also common to find other abnormal changes, such as fiber cord shadow (22.73%), lung markings fuzzy disorder (30%), pulmonary nodules (11.82%), emphysema (9.09%), bronchiectasis (3.64%), subpleural nodules (11.82%) and pleural thickening (24.55%). In treatment, honeycombing and subpleural nodules were more common in patients with methotrexate (MTX) and/or leflunomide treatment than without (P < 0.05). Other abnormal changes were no statistical significance (P > 0.05). Pulmonary involvement is common in RA patients, and it is suggested that HRCT could be a sensitive and useful way in evaluating the lung of RA patients.