- Inhibitory effects of tubeimoside I on synoviocytes and collagen-induced arthritis in rats. [Journal Article]
- JCJ Cell Physiol 2018 May 15
- Advancements in rheumatoid arthritis (RA) therapies have shown considerable progresses in the comprehension of disease. However, the development of new potential medicines with relative safety and ef...
Advancements in rheumatoid arthritis (RA) therapies have shown considerable progresses in the comprehension of disease. However, the development of new potential medicines with relative safety and efficacy continues and natural compounds have been considered as alternatives or complementary agents to gain immense attractions. Tubeimoside I (TBMS I), a main triterpenoid saponin isolated from Bolbostemma paniculatum, has been reported to possess antiviral and anticancer effects. However, its effect on RA remains unknown. Here, we investigated the therapeutic effect of TBMS I in collagen-induced arthritis (CIA) rats and explored its underlying mechanism. Our results showed that TBMS I treatment efficaciously ameliorated inflammation and joint destruction of rats with CIA. In vitro studies revealed that TBMS I suppressed the production of pro-inflammatory cytokines including IL-1β, IL-6, IL-8 and TNFα, and downregulated the expression of MMP-9. In addition, TBMS I attenuated the destructive phenotypes of FLS of CIA rats including inhibiting proliferation and reducing migration rate. Further mechanistic analysis demonstrated that TBMS I suppressed TNFα-induced activations of NF-κB and MAPKs (p38 and JNK) leading to the downregulation of pro-inflammatory cytokines, which was beneficial to the anti-proliferative and anti-migratory activities of FLS cells. Taken together, TBMS I has a great potential to be developed into a novel therapeutic agent for the treatment of RA.
- TL1A mediates fibroblast-like synoviocytes migration and Indian Hedgehog signaling pathway via TNFR2 in patients with rheumatoid arthritis. [Journal Article]
- ECEur Cytokine Netw 2018 Mar 01; 29(1):27-35
- Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joints inflammation. One of the aggressive characteristics of RA fibroblast-like synoviocytes (FLS) is the tendency for migr...
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joints inflammation. One of the aggressive characteristics of RA fibroblast-like synoviocytes (FLS) is the tendency for migration in the local environment, which plays a central role in the RA pathogenesis. Tumor Necrosis Factor (TNF)-like cytokine 1A (TL1A) is a member of TNF superfamily, which has a role in autoimmunity and influences the RA-FLS behavior through TNF receptor 2 (TNFR2). We investigated the effect of TNF-like cytokine 1A (TL1A) on RA-FLS migration using patients' samples. Specifically, we examined the hedgehog signaling pathway which is a key regulator in chondrocyte growth and differentiation. We found that TL1A increased significantly the hedgehog homologue Indian hedgehog (IHH) and its receptor Patched 1, 2 (PTCH 1, 2) in RA-FLS. In addition, TL1A-stimulated RA-FLS promoted significantly IHH protein expression. However, both mRNA and protein levels decreased substantially after blocking TL1A with TNFR2 antagonist. The migratory property of RA-FLS was enhanced after stimulation of RA-FLS with TL1A, but was compromised following TL1A blockage. In conclusion, our study has revealed that TL1A modulated RA-FLS migration and Indian hedgehog signaling pathway using TNFR2.
- Imaging, myeloid precursor immortalization, and genome editing for defining mechanisms of leukocyte recruitment in vivo. [Journal Article]
- TTheranostics 2018; 8(9):2407-2423
- Recruitment of leukocytes from the blood to sites of inflammation poses a promising target for new diagnostic and therapeutic approaches. We aimed to develop a novel method to non-invasively analyze ...
Recruitment of leukocytes from the blood to sites of inflammation poses a promising target for new diagnostic and therapeutic approaches. We aimed to develop a novel method to non-invasively analyze molecular mechanisms of leukocyte migration in pre-clinical models of inflammation in vivo. Methods: We used the ER-HoxB8 system to transiently immortalize murine myeloid precursors from wildtype and CD18- as well as MRP14-deficient mice. A VLA4α-/- cell line was generated by CRISPR/Cas9-mediated gene editing. We analyzed the migration of wildtype and knockout leukocytes in vivo by optical and nuclear imaging in mice with irritant contact dermatitis, cutaneous granuloma, experimental arthritis and myocardial infarction. Results: Transient immortalization, gene editing and in vivo imaging can be combined to analyze migratory mechanisms of murine leukocytes, even for gene deletions resulting in lethal phenotypes in mice. We reliably confirmed known migratory defects of leukocytes deficient for the adhesion molecules CD18 or VLA4α. Also, using our new method we identified a new role of the most abundant calcium-binding proteins in phagocytes and major alarmins in many inflammatory diseases, MRP8 and MRP14, for transmigration in vivo. Conclusion: We provide a combinatorial approach to rapidly characterize molecular mechanisms of leukocyte recruitment in vivo, with the potential to aid in identification of diagnostic and therapeutic targets in inflammatory pathologies.
- A rare cause of oligoarthritis with septic presentation. [Journal Article]
- BCBMJ Case Rep 2018 Apr 17; 2018
- A 33-year-old man presented with new-onset, asymmetric, migratory oligoarthritis in the setting of several weeks of nausea and vomiting, diarrhoea, fevers and dysuria. He was initially treated in the...
A 33-year-old man presented with new-onset, asymmetric, migratory oligoarthritis in the setting of several weeks of nausea and vomiting, diarrhoea, fevers and dysuria. He was initially treated in the inpatient setting with broad-spectrum antibiotics due to concern for an evolving sepsis presentation. Arthrocentesis of a large right knee effusion revealed inflammatory synovial fluid without findings suggestive of septic arthritis. Human leucocyte antigen B27 was positive and, taken together with the antecedent history of gastroenteritis, dysuria and inflammatory oligoarthritis, the clinical diagnosis was most consistent with reactive arthritis. Antibiotics were discontinued. His treatment course proved refractory to non-steroidal anti-inflammatory drugs and intra-articular and systemic glucocorticoid therapy with concurrent use of sulfasalazine and ultimately necessitated treatment with a tumour necrosis factor alpha inhibitor.
- Follistatin-like 1 in development and human diseases. [Review]
- CMCell Mol Life Sci 2018 Mar 29
- Follistatin-like 1 (FSTL1) is a secreted glycoprotein displaying expression changes during development and disease, among which cardiovascular disease, cancer, and arthritis. The cardioprotective rol...
Follistatin-like 1 (FSTL1) is a secreted glycoprotein displaying expression changes during development and disease, among which cardiovascular disease, cancer, and arthritis. The cardioprotective role of FSTL1 has been intensively studied over the last years, though its mechanism of action remains elusive. FSTL1 is involved in multiple signaling pathways and biological processes, including vascularization and regulation of the immune response, a feature that complicates its study. Binding to the DIP2A, TLR4 and BMP receptors have been shown, but other molecular partners probably exist. During cancer progression and rheumatoid arthritis, controversial data have been reported with respect to the proliferative, apoptotic, migratory, and inflammatory effects of FSTL1. This controversy might reside in the extensive post-transcriptional regulation of FSTL1. The FSTL1 primary transcript also encodes for a microRNA (miR-198) in primates and multiple microRNA-binding sites are present in the 3'UTR. The switch between expression of the FSTL1 protein and miR-198 is an important regulator of tumour metastasis and wound healing. The glycosylation state of FSTL1 is a determinant of biological activity, in cardiomyocytes the glycosylated form promoting proliferation and the non-glycosylated working anti-apoptotic. Moreover, the glycosylation state shows differences between species and tissues which might underlie the differences observed in in vitro studies. Finally, regulation at the level of protein secretion has been described.
- Chemokines beyond chemo-attraction: CXCL10 and its significant role in cancer and autoimmunity. [Journal Article]
- CCytokine 2018 Feb 12
- Chemokines are mostly known for their chemotactic properties, and less for their ability to direct the biological function of target cells, including T cells. The current review focuses on a key chem...
Chemokines are mostly known for their chemotactic properties, and less for their ability to direct the biological function of target cells, including T cells. The current review focuses on a key chemokine named CXCL10 and its role in directing the migratory propertied and biological function of CD4+ and CD8+ T cells in the context of cancer and inflammatory autoimmunity. CXCR3 is a chemokine receptor that is abundant on CD4+ T cells, CD8+ T cells and NK cells. It has three known ligands: CXCL9, CXCL10 and CXCL11. Different studies, including those coming form our laboratory, indicated that aside of attracting CD8+ and CD4+ effector T cells to tumor sites and sites of inflammation CXCL10 directs the polarization and potentiates the biological function of these cells. This makes CXCL10 a "key driver chemokine" and a valid target for therapy of autoimmune diseases such as Inflammatory Bowl's Disease, Multiple Sclerosis, Rheumatoid arthritis and others. As for cancer this motivated different groups, including our group to develop CXCL10 based therapies for cancer due to its ability to enhance T-dependent anti cancer immunity. The current review summarizes these findings and their potential translational implication.
- The RORγt-CCR6-CCL20 axis augments Th17 cells invasion into the synovia of rheumatoid arthritis patients. [Journal Article]
- MRMod Rheumatol 2018 Jan 22; :1-12
- CONCLUSIONS: The high expression of RORγt might facilitate the migration of Th17 cells to inflamed joints via the enhanced expression of CCR6 and contribute to the pathology of RA.
- Streptococcal tonsillitis related reactive arthritis - clinical, ultrasound imaging and immunohistochemical study. [Journal Article]
- RJRom J Morphol Embryol 2017; 58(3):801-807
- In clinical practice and literature studies, the most common condition associated to streptococcal tonsillitis used to be acute rheumatic fever (ARF). Several publications in the late years report a ...
In clinical practice and literature studies, the most common condition associated to streptococcal tonsillitis used to be acute rheumatic fever (ARF). Several publications in the late years report a more frequent and distinctive entity from ARF following β-hemolytic group A streptococcus infection in patients with post-infectious arthritis, that do not fulfill the modified Jones criteria, the so-called post-streptococcal reactive arthritis (PSRA). A distinctive pattern of clinical framing and biological profile in patients with PSRA following streptococcal tonsillitis is described, with a non-migratory, additive, recent onset (7-10 days) arthritis that affects small and large joints as well, with a bimodal peak of incidence at 8-14 and 21-37 years of age, with variate response to non-steroidal anti-inflammatory drugs and has a tendency for recurrence and persistence. Sacroiliitis, although rare, is described in human leukocyte antigen (HLA)-B27 positive PSRA patients. The main objective of the current study was to evaluate various immunohistochemical patterns of streptococcal tonsillitis in patients with PSRA and find possible correlations with the clinical, biological and ultrasound profile.
- Colon adenocarcinoma after jejunoileal bypass for morbid obesity. [Journal Article]
- JSJ Surg Case Rep 2017; 2017(11):rjx214
- Jejunoileal bypass (JIB) was developed as a surgical treatment for morbid obesity in the early 1950s. However, this procedure is now known to be associated with multiple metabolic complications and h...
Jejunoileal bypass (JIB) was developed as a surgical treatment for morbid obesity in the early 1950s. However, this procedure is now known to be associated with multiple metabolic complications and has subsequently been abandoned as a viable bariatric procedure. Some of these known complications include renal stone formation, liver failure, migratory arthritis, fat-soluble deficiencies, blind-loop syndrome and severe diarrhea. Additionally, there have been animal models suggesting colon dysplasia after JIB. To our knowledge however, in humans, no colon cancers have been attributed to JIB in the literature. Here we report a 63-year-old morbidly obese female who had a JIB surgery in 1973 and subsequently was found to have numerous sessile colonic polyps throughout her colon and adenocarcinoma of the ascending colon without any family history of colonic polyposis syndromes or colon cancer.
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- SAPHO syndrome associated with hidradenitis suppurativa and pyoderma gangrenosum successfully treated with adalimumab and methotrexate: a case report and review of the literature. [Review]
- IJInt J Dermatol 2018; 57(1):10-18
- SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is a rare inflammatory condition describing the combination of skin, bone, and joint manifestations that has a heterogeneous p...
SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is a rare inflammatory condition describing the combination of skin, bone, and joint manifestations that has a heterogeneous presentation. We report a case of severe SAPHO syndrome in association with hidradenitis suppurativa and pyoderma gangrenosum in a 27-year-old male. The patient had an initial migratory arthritis affecting the knees, ankles, metacarpophalangeal joints, proximal interphalangeal joints, wrists, shoulder, and lower back, which progressed to a persistent arthritis and swelling at the sternum, shoulders, wrists, hands, feet, and lower back. Radiographic changes were consistent with the diagnosis of SAPHO syndrome. Serum proinflammatory cytokine levels were significantly elevated and improved substantially after 3 months of therapy. Rationale for therapy in this patient was the observation that tumor necrosis alpha antagonists have been successfully used in SAPHO syndrome, and since arthropathy was so prominent in our patient, we elected to use adalimumab combined with methotrexate.