METHODS AND MATERIALS: Hyperuricemia model was performed in male Swiss Webster mice. Intraperitoneally injection of uric acid (125mg/kg body weight) was done for 7 and 14 days (UA7 and UA14 groups). Meanwhile, the UAL groups were injected with uric acid and followed by the administration of allopurinol (UAL7 and UAL14 groups). On the due date, mice were sacrificed, and liver was harvested. Uric acid, SGOT, SGPT, and albumin level were measured from the serum. The mRNA expression of TLR4, MCP1, CD68, and collagen1 were assessed through RT-PCR. Liver fibrosis was quantified through Sirius red staining, while the number of hepatic stellates cells (HSCs) and TLR4 were assessed through IHC staining.
RESULTS: Uric acid induction for 7 and 14 days stimulated an increase of both SGOT and SGPT serum levels. Followed by enhanced inflammatory mediators: Toll-like receptor-4 (TLR- 4), Monocyte Chemoattractant Protein-1 (MCP-1) and Cluster of Differentiation 68 (CD68) mRNA expression in the liver (p<0.05). The histological findings showed that the UA7 and UA14 groups had higher liver fibrosis scores (p<0.05), collagen I mRNA expression (p<0.05), and the number of HSCs (p<0.05) compared to Control group. Administration of allopurinol showed amelioration of uric acid and liver enzymes levels which followed by inflammatory mediators, liver fibrosis and collagen1, and hepatic stellate cells significantly.
CONCLUSION: Therefore, uric acid augmented the liver fibrosis by increasing the number of hepatic stellate cells.
METHODS: This is a dual-center randomized controlled trial (RCT). Sixty-nine patients aged 18 to 55 years with International Cartilage Repair Society grade 3 and 4 chondral lesions (size ≥3 cm2) of the knee joint were randomized equally into (1) a control group receiving intra-articular injections of HA plus physiotherapy and (2) an intervention group receiving arthroscopic subchondral drilling into chondral defects and postoperative intra-articular injections of PBSCs plus HA. The coprimary efficacy endpoints were subjective International Knee Documentation Committee (IKDC) and Knee Injury and Osteoarthritis Outcome Score (KOOS)-pain subdomain measured at month 24. The secondary efficacy endpoints included all other KOOS subdomains, Numeric Rating Scale (NRS), and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scores.
RESULTS: At 24 months, the mean IKDC scores for the control and intervention groups were 48.1 and 65.6, respectively (P < .0001). The mean for KOOS-pain subdomain scores were 59.0 (control) and 86.0 (intervention) with P < .0001. All other KOOS subdomain, NRS, and MOCART scores were statistically significant (P < .0001) at month 24. Moreover, for the intervention group, 70.8% of patients had IKDC and KOOS-pain subdomain scores exceeding the minimal clinically important difference values, indicating clinical significance. There were no notable adverse events that were unexpected and related to the study drug or procedures.
CONCLUSIONS: Arthroscopic marrow stimulation with subchondral drilling into massive chondral defects of the knee joint followed by postoperative intra-articular injections of autologous PBSCs plus HA is safe and showed a significant improvement of clinical and radiologic scores compared with HA plus physiotherapy.
LEVEL OF EVIDENCE: Level I, RCT.
Methods: Chemical profiling of P. blanda was carried out using gas chromatography mass spectrometry (GCMS) followed by isolation of bioactive compounds by column chromatography. DPPH• and FRAP assays were used to evaluate antioxidant activity and the MTT assay was performed to estimate the cytotoxicity activity against three cancer cell lines, namely MCF-7, HL-60 and WEHI-3, and three normal cell lines, MCF10A, WRL-68 and HDFa.
Results: X-ray crystallographic data for peperomin A is reported for the first time here and N,N'-diphenethyloxamide was isolated for the first time from Peperomia blanda. Methanol and dichloromethane extracts showed high radical scavenging activity with an IC50 of 36.81 ± 0.09 µg/mL, followed by the dichloromethane extract at 61.78 ± 0.02 µg/mL, whereas the weak ferric reducing activity of P. blanda extracts ranging from 162.2 ± 0.80 to 381.5 ± 1.31 µg/mL were recorded. In addition, petroleum ether crude extract exhibited the highest cytotoxic activity against all the tested cancer cell lines with IC50 values of 9.54 ± 0.30, 4.30 ± 0.90 and 5.39 ± 0.34 µg/mL, respectively. Peperomin A and the isolated mixture of phytosterol (stigmasterol and β-sitosterol) exhibited cytotoxic activity against MCF-7 and WE-HI cell lines with an IC50 of (5.58 ± 0.47, 4.62 ± 0.03 µg/mL) and (8.94 ± 0.05, 9.84 ± 0.61 µg/mL), respectively, compared to a standard drug, taxol, that has IC50 values of 3.56 ± 0.34 and 1.90 ± 0.9 µg/mL, respectively.
Conclusion: The activities of P. blanda extracts and isolated compounds recorded in this study underlines the potential that makes this plant a valuable source for further study on anticancer and antioxidant activities.