Objectives To evaluate the main symptoms of knee osteoarthritis (OA) and tissue structure changes after a single dose bone marrow-derived mononuclear cell (BM MNC) intra articular injection. Case series study. Patients with knee OA Kellgren Lawrence (K-L) grade II and III received 1 injection of BM MNC. The clinical results were analyzed with the Knee injury and Osteoarthritis Outcome Score (KOOS) and Knee Society Score (KSS) before, 3, 6, and 12 months after injection. Radiological evaluation was performed with a calibrated x-ray and the magnetic resonance (MR) imaging before and 6 to 7 months postinjection. Results A total of 34 knees were treated with BM MNC injections. Mean (±SD) age of patient group was 53.96 ± 14.15 years; there were 16 males, 16 females, KL grade II, 16; KL grade III, 18. The average injected count of BM MNCs was 45.56 ± 34.94 × 10 cells. At the endpoint of 12 months 65% of patients still had minimal perceptible clinical improvement of the KOOS total score. The mean improvement of KOOS total score was +15.3 and of the KSS knee score was +21.45 and the function subscale +27.08 ( P < 0.05) points. The Whole Organ Magnetic Resonance Imaging Score (WORMS) improved from 44.31 to 42.93 points ( P < 0.05). No adverse effects after the BM-MNC injection were observed. Conclusions The single dose BM MNC partially reduces clinical signs of the knee osteoarthritis stage II/III and in some cases, decreases degenerative changes in the joint building tissue over 12-month period.

Viral mRNA cap methyltransferases (MTases) are emerging targets for the development of broad-spectrum antiviral agents. In this work, we designed potential SARS-CoV-2 MTase Nsp14 and Nsp16 inhibitors by using bioisosteric substitution of the sulfonium and amino acid substructures of the cosubstrate S-adenosylmethionine (SAM), which serves as the methyl donor in the enzymatic reaction. The synthetically accessible target structures were prioritized using molecular docking. Testing of the inhibitory activity of the synthesized compounds showed nanomolar to submicromolar IC 50 values for five compounds. To evaluate selectivity, enzymatic inhibition of the human glycine N -methyltransferase involved in cellular SAM/SAH ratio regulation was also determined, which indicated that the discovered compounds are nonselective inhibitors of the studied MTases with slight selectivity for Nsp16. No cytotoxic effects were observed; however, this is most likely a result of the poor cell permeability of all evaluated compounds.

The intra-articular injection of bone marrow-derived mononuclear cells is a safe manipulation with no side effects during the 12-month period. This treatment provides statistically significant clinical improvement between the starting point and 1, 3, 6, and 12 months after. When compared to hyaluronic acid treatment, better pain relief in the long-term period of mononuclear cell group was observed.