The varying clinical effectiveness of single, three and five intraarticular injections of platelet-rich plasma in knee osteoarthritis.

OBJECTIVE: To investigate the variations in clinical effectiveness among patients diagnosed with knee osteoarthritis who underwent intra-articular administration of platelet-rich plasma using single, triple, or quintuple injections. METHODS: One hundred twenty patients with grade I-III knee osteoarthritis were randomly assigned to three groups: PRP1 group, who received a single injection of platelet-rich plasma; PRP3 group, who received three PRP injections one week apart; PRP5 group, who received five PRP injections one week apart. The patients' conditions were evaluated using the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Arthritis Index-VA3.1 version (WOMAC-VA3.1) at baseline and 6, 12, 24, and 52 weeks 52 weeks follow up. RESULTS: Out of the total participants, 106 patients (30 males and 76 females) completed the study. The primary outcome measure, WOMAC pain score, registered significant improvements across all groups when compared to pre-treatment levels. However, the application of 3 and 5 injections of platelet-rich plasma was substantially more effective than that of a single injection in reducing knee pain and stiffness, as well as enhancing physical function in patients with knee osteoarthritis. No statistically discernable difference was observed between PRP3 and PRP5 at all follow-up intervals, and there was no discernable difference between 3 and 5 PRP injections either. Mild side effects occurred in all three groups. CONCLUSIONS: The administration of three or five injections of platelet-rich plasma is safe, substantially more effective than single injections, and leads to remarkable clinical improvement by significantly reducing knee pain, improving joint stiffness, and enhancing physical function in patients with grade I-III knee osteoarthritis. Furthermore, no significant difference was observed in the efficacy of three or five injections. Therefore, we recommend using three injections of PRP in the treatment of patients with knee osteoarthritis of grade I-III.

Phytophthora infestans RXLR effector Pi23014 targets host RNA-binding protein NbRBP3a to suppress plant immunity.

Phytophthora infestans is a destructive oomycete that causes the late blight of potato and tomato worldwide. It secretes numerous small proteins called effectors in order to manipulate host cell components and suppress plant immunity. Identifying the targets of these effectors is crucial for understanding P. infestans pathogenesis and host plant immunity. In this study, we show that the virulence RXLR effector Pi23014 of P. infestans targets the host nucleus and chloroplasts. By using a liquid chromatogrpahy-tandem mass spectrometry assay and co-immunoprecipitation assasys, we show that it interacts with NbRBP3a, a putative glycine-rich RNA-binding protein. We confirmed the co-localization of Pi23014 and NbRBP3a within the nucleus, by using bimolecular fluorescence complementation. Reverse transcription-quantitative PCR assays showed that the expression of NbRBP3a was induced in Nicotiana benthamiana during P. infestans infection and the expression of marker genes for multiple defence pathways were significantly down-regulated in NbRBP3-silenced plants compared with GFP-silenced plants. Agrobacterium tumefaciens-mediated transient overexpression of NbRBP3a significantly enhanced plant resistance to P. infestans. Mutations in the N-terminus RNA recognition motif (RRM) of NbRBP3a abolished its interaction with Pi23014 and eliminated its capability to enhance plant resistance to leaf colonization by P. infestans. We further showed that silencing NbRBP3 reduced photosystem II activity, reduced host photosynthetic efficiency, attenuated Pi23014-mediated suppression of cell death triggered by P. infestans pathogen-associated molecular pattern elicitor INF1, and suppressed plant immunity.

Impact of autologous platelet-rich plasma therapy vs. hyaluronic acid on synovial fluid biomarkers in knee osteoarthritis: a randomized controlled clinical trial.

Objective: Observe the effects of platelet-rich plasma (PRP) therapy on inflammatory cytokines in the synovial fluid of the knee joint of patients with KOA, and explore the effects of PRP intra-articular injection on the inflammation of the knee joint environment and the possible mechanism of action. Methods: Seventy patients were randomized to undergo three blinded weekly intra-articular injections of PRP or hyaluronic acid (HA). The concentrations of inflammatory cytokines, including interleukin (IL)-6, IL-1ß, tumor necrosis factor (TNF)-α, IL-8, IL-17A, IL-17F, IL-4, IL-5, and IL-10, in the synovial fluid were evaluated before the intervention and 1 month after the third injection. The Western Ontario and McMaster University (WOMAC) and visual analog scale (VAS) scores were used to assess pain and functional status of the knee joints in both groups before the intervention, immediately post-intervention, and 1, 3, 6, and 12 months after the intervention. Results: Baseline characteristics were similar in both groups with no statistical difference. The IL-6, IL-1ß, TNF-α, IL-17A, and IL-10 levels in the synovial fluid of the observation group decreased significantly after, vs. before, the intervention (p < 0.05), whereas the IL-8, IL-17F, and IL-4 levels decreased (p > 0.05) and IL-5 levels increased (p > 0.05). There was no statistically significant difference between inflammatory cytokine levels in the synovial fluid of the samples from the control group before and after the intervention (p > 0.05). There were no statistically significant differences between the two groups immediately after intervention (p > 0.05). At 1, 3, 6, and 12 months after intervention, the WOMAC and VAS scores were significantly better in the observation group than in the control group (p < 0.05). Conclusion: Platelet plasma therapy can reduce the concentrations of inflammatory cytokines IL-6, IL-1ß, TNF-α, IL-17A, and IL-10 in the synovial fluid of KOA patients, reduce the expression levels of IL-8, IL-17F, and IL-4, clear the pro-inflammatory factors, improve the inflammatory environment of the affected knee joint, and alleviate pain caused by inflammation. Thus, alleviating pain and improving knee function in patients with KOA.

Macular microcirculation changes after repair of rhegmatogenous retinal detachment assessed with optical coherence tomography angiography: A systematic review and meta-analysis.

Purpose: The aim of the study was to investigate microcirculation changes in the macula evaluated by optical coherence tomography angiography (OCTA)in patients receiving anatomical repair after surgery for rhegmatogenous retinal detachment (RRD). Methods: A literature search was conducted in PubMed, EMBASE, Web of Science and the Cochrane Library. Studies including patients with macula-on or macula-off RRD and repaired successfully through primary surgery were selected. Foveal avascular zone (FAZ) area and macular vascular density (VD) in both the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were analyzed using RevMan 5.4 software. Results: Twelve studies including 430 RRD eyes and 430 control eyes were selected. In eyes with macula-on RRD, FAZ area, VD in the foveal SCP and DCP, and VD in the parafoveal SCP and DCP were not altered compared with control eyes, after the retina was reattached. In eyes with macula-off RRD that was repaired successfully through surgery, FAZ area in the DCP (0.13 mm2, 95% CI: 0.02 to 0.25, p = 0.02) remained enlarged compared with control eyes. Meanwhile, VD in the foveal DCP was also significantly reduced (-3.12%, 95% CI: -6.15 to -0.09%, p = 0.04), even though retinal reattachment was achieved by surgery in eyes with macula-off RRD. Conclusion: In patients with macula-off rhegmatogenous retinal detachment, foveal avascular zone area in the deep capillary plexuses was enlarged and vascular density in the foveal deep capillary plexus was reduced, even after the retina was successfully reattached through a primary surgery.

The novel peptide NbPPI1 identified from Nicotiana benthamiana triggers immune responses and enhances resistance against Phytophthora pathogens.

In plants, recognition of small secreted peptides, such as damage/danger-associated molecular patterns (DAMPs), regulates diverse processes, including stress and immune responses. Here, we identified an SGPS (Ser-Gly-Pro-Ser) motif-containing peptide, Nicotiana tabacum NtPROPPI, and its two homologs in Nicotiana benthamiana, NbPROPPI1 and NbPROPPI2. Phytophthora parasitica infection and salicylic acid (SA) treatment induced NbPROPPI1/2 expression. Moreover, SignalP predicted that the 89-amino acid NtPROPPI includes a 24-amino acid N-terminal signal peptide and NbPROPPI1/2-GFP fusion proteins were mainly localized to the periplasm. Transient expression of NbPROPPI1/2 inhibited P. parasitica colonization, and NbPROPPI1/2 knockdown rendered plants more susceptible to P. parasitica. An eight-amino-acid segment in the NbPROPPI1 C-terminus was essential for its immune function and a synthetic 20-residue peptide, NbPPI1, derived from the C-terminus of NbPROPPI1 provoked significant immune responses in N. benthamiana. These responses led to enhanced accumulation of reactive oxygen species, activation of mitogen-activated protein kinases, and up-regulation of the defense genes Flg22-induced receptor-like kinase (FRK) and WRKY DNA-binding protein 33 (WRKY33). The NbPPI1-induced defense responses require Brassinosteroid insensitive 1-associated receptor kinase 1 (BAK1). These results suggest that NbPPI1 functions as a DAMP in N. benthamiana; this novel DAMP provides a potentially useful target for improving plant resistance to Pytophthora pathogens.