Rutin Inhibits the Progression of Osteoarthritis Through CBS -Mediated RhoA/ROCK Signaling

Zhao

et al. 2023

Preprint

In July 2022, the World Health Organization announced monkeypox as a public health emergency of international concern (PHEIC), over 85,000 global cases have been reported currently. However, preventive and therapeutic treatments are very limited. The monkeypox virus (MPXV) E12, an mRNA capping enzyme small subunit, is essential for the methyltransferase activity of RNA capping enzymes of MPXV. Here, we solved a 2.16 angstrom crystal structure of E12. We also docked the D1 subunit c-terminal domain (D1CTD) of vaccinia virus (VACV) with E12 to analyze the critical residues of interface between them. These residues are used for drug screening. The top six compounds are Rutin, Quercitrin, Epigallocatechin, Rosuvastatin, 5-hydroxy-L-Tryptophan, and Deferasirox. These findings may provide insights into the development of anti-MPXV drugs.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Crystal structure of mRNA cap (guanine-N7) methyltransferase E12 subunit from monkeypox virus and discovery of its inhibitors

Zhao

et al. 2023

Preprint

J Biochem & Molecular Tox

“…[35] Rutin can inhibit the inflammatory, extracellular matrix degeneration, and oxidative stress progression of OA. [36][37][38] Forsythoside B, a conventional drug, has been reported to boast an anti-inflammatory activity in the context of diverse diseases correlated with inflammation. [39] Predicated on the studies, we Reportedly, in the course of oxidative stress, chondrocyte lipid peroxidation contributes to collagen fragmentation, and such a mechanical fatigue failure may result in OA.…”

Section: Discussionmentioning

confidence: 99%

“…[ 35 ] Rutin can inhibit the inflammatory, extracellular matrix degeneration, and oxidative stress progression of OA. [ 36–38 ] Forsythoside B, a conventional drug, has been reported to boast an anti‐inflammatory activity in the context of diverse diseases correlated with inflammation. [ 39 ] Predicated on the studies, we boldly conjectured that Forsythoside B could influence OA occurrence and progression as well.…”

Section: Discussionmentioning

confidence: 99%

Forsythoside B alleviates osteoarthritis through the HMGB1/TLR4/NF‐κB and Keap1/Nrf2/HO‐1 pathways

Li,

Hou

et al. 2023

Osteoarthritis (OA) is a joint pain and dysfunction syndrome resulting from severe joint degeneration. Inflammation and degeneration of the articular cartilage are two main features of OA and have tight interactions during OA progression. Conventional treatment with nonsteroidal anti‐inflammatory drugs has been widely utilized clinically, whereas the side effects have restricted their application. Forsythoside B has been found with anti‐inflammatory effects and antiapoptosis in inflammatory diseases, whereas in OA it remains poorly understood. Interleukin (IL)−1β (10 ng/mL) was taken to induce an OA cell model on HC‐A chondrocytes and an OA rat model was constructed for in vivo experiments. Forsythoside B was adopted to treat HC‐A chondrocytes and OA rats. As shown by the data, Forsythoside B hampered IL‐1β‐elicited rat chondrocyte apoptosis, oxidative stress, and facilitated proliferation. The profiles of inflammatory factors, NOD‐like receptor family pyrin domain containing 3 inflammasomes, Kelch‐like epichlorohydrin‐associated protein‐1 (Keap1), and nuclear factor‐κB (NF‐κB) phosphorylation were suppressed by Forsythoside B, whereas the nuclear factor E2‐related factor 2 (Nrf2) and heme oxygenase‐1 (HO‐1) levels were promoted. Further, Forsythoside B mitigated cartilage damage and degeneration. Moreover, the oxidative stress and inflammation mediators in the cartilage tissue of OA rats were remarkably abated. Collectively, Forsythoside B hinders the NF‐κB and Keap1/Nrf2/HO‐1 pathways to curb IL‐1β‐elicited OA rat oxidative stress and inflammation both in vivo and ex vivo, ameliorating OA development. All over, this study provides an underlying strategy for treating OA, which might help the clinical treatment of OA patients.

“…ImageJ 1.53K (National Institutes of Health) was used to analyze the fluorescence area of images. Immunocytochemistry was performed as previously described ( 38 ). Briefly, cells were plated in a 24-well plate, and after adhesion, were fixed with 4% paraformaldehyde at room temperature for 30 min, and immunofluorescence was performed as aforementioned.…”

Section: Methodsmentioning

confidence: 99%

LPS combined with CD47mAb enhances the anti‑osteosarcoma ability of macrophages

et al. 2023

Self Cite

Macrophages are abundant in tumor tissues, and they affect the biological properties of tumor cells. The present findings indicated that osteosarcoma (OS) has a high proportion of tumor-promoting M2 macrophages. The CD47 protein can aid tumor cells in their immunological escape. It was identified that CD47 protein is abundant in both clinical OS tissues and OS cell lines. Lipopolysaccharide (LPS) is an activator of Toll-like receptor 4 present on the surface of macrophages, and it induces the polarization towards a pro-inflammatory phenotype; and macrophages of pro-inflammatory phenotype may present antitumor potential. CD47 monoclonal antibody (CD47mAb) can block the CD47-SIRPα signaling pathway, thus enhancing the antitumor ability of macrophages. Immunofluorescence staining confirmed that OS was rich in CD47 protein and M2 macrophages. In the present study, the antitumor potential of macrophages activated using LPS combined with the CD47mAb was assessed. LPS combined with CD47mAb greatly improved macrophages' capacity to phagocytize OS cells, according to the laser confocal experiments and flow cytometry. Furthermore, cell proliferation analysis, cell migration assay and apoptosis determination confirmed LPS-polarized macrophages might efficiently suppress OS cells growth and migration while promoting apoptosis. Taken together, the results of present study demonstrated that LPS combined with CD47mAb enhanced the anti-osteosarcoma ability of macrophages.