Engineered hsa-miR-455-3p-Abundant Extracellular Vesicles Derived from 3D-Cultured Adipose Mesenchymal Stem Cells for Tissue-Engineering Hyaline Cartilage Regeneration.

Efforts are made to enhance the inherent potential of extracellular vesicles (EVs) by utilizing 3D culture platforms and engineered strategies for functional cargo-loading. Three distinct types of adipose mesenchymal stem cells-derived EVs (ADSCs-EVs) are successfully isolated utilizing 3D culture platforms consisting of porous gelatin methacryloyl (PG), PG combined with sericin methacryloyl (PG/SerMA), or PG combined with chondroitin sulfate methacryloyl (PG/ChSMA). These correspond to PG-EVs, PG/SerMA-EVs, and PG/ChSMA-EVs, respectively. Unique microRNA (miRNA) profiles are observed in each type of ADSCs-EVs. Notably, PG-EVs encapsulate higher levels of hsa-miR-455-3p and deliver more hsa-miR-455-3p to chondrocytes, which results in the activation of the hsa-miR-455-3p/PAK2/Smad2/3 axis and the subsequent hyaline cartilage regeneration. Furthermore, the functionality of PG-EVs is optimized through engineered strategies, including agomir/lentivirus transfection, electroporation, and Exo-Fect transfection. These strategies, referred to as Agomir-EVs, Lentivirus-EVs, Electroporation-EVs, and Exo-Fect-EVs, respectively, are ranked based on their efficacy in encapsulating hsa-miR-455-3p, delivering hsa-miR-455-3p to chondrocytes, and promoting cartilage formation via the hsa-miR-455-3p/PAK2/Smad2/3 axis. Notably, Exo-Fect-EVs exhibit the highest efficiency. Collectively, the 3D culture conditions and engineered strategies have an impact on the miRNA profiles and cartilage regeneration capabilities of ADSCs-EVs. The findings provide valuable insights into the mechanisms underlying the promotion of cartilage regeneration by ADSCs-EVs.

The protective effect of traditional Chinese medicine Jinteng Qingbi granules on rats with rheumatoid arthritis.

Introduction: Jinteng Qingbi granules (JTQBG), a traditional Chinese medicine formulation, are widely used for the treatment of rheumatoid arthritis (RA) due to their satisfactory therapeutic efficacy. However, the underlying mechanism of action remains unclear. This study aims to investigate the protective effects of JTQBG against RA and elucidates its potential molecular mechanisms. Methods: A collagen-induced arthritis (CIA) rat model was utilized, and JTQBG (1.25, 2.5, 5 g/kg/day) or methotrexate (MTX, 1 mg/kg/week) was orally administered. The rats' weight, arthritis index (AI), and paw volume were measured weekly. Synovial hyperplasia of the joints was detected using a small animal ultrasound imaging system. Joint destruction was assessed using an X-ray imaging system. Histopathological examinations were performed using hematoxylin-eosin (H&E), Saffron-O and fast green staining. Serum inflammatory cytokines were detected using ELISA. Furthermore, 4D label-free quantitative proteomics of synovial tissues and non-targeted metabolomics of blood serum were conducted to analyze the molecular mechanisms. Results: JTQBG exerted a significant therapeutic effect on CIA rats by reducing inflammatory cell infiltration, synovial hyperplasia, cartilage erosion, and bone destruction. It also decreased the spleen index, inhibited hyperplasia of the white pulp, and decreased the serum levels of IL-1ß and IL-18. Proteomics analysis identified 367 differentially expressed proteins (DEPs) between the Model and Normal groups, and 71 DEPs between the JTQBG and Model groups. These DEPs were significantly enriched in the NF-κB pathway. 11 DEPs were significantly reversed after treatment with JTQBG. Western blot results further validated the expression levels of Nfkb1, Pdk1, and Pecam1, and analyzed the expression levels of p-IKK, p-IκBα, and IκBα. The therapeutic efficacy of JTQBG was partly attributed to the suppression of the NF-κB pathway in synovial tissues. Serum metabolomics identified 17 potential biomarkers for JTQBG treatment of CIA rats, which were closely related to Alanine, aspartate and glutamate metabolism, Tryptophan metabolism, Ascorbate and aldarate metabolism, Arginine metabolism, and Inositol phosphate metabolism. Conclusion: Our findings demonstrated that JTQBG was effective against RA by alleviating synovial inflammation, synovial hyperplasia, and joint destruction. The anti-RA properties of JTQBG were likely attributed to the inhibition of the NF-κB pathway and the regulation of serum metabolite disorders.

Paenibacillus lacisoli sp. nov., a mesotrione-degrading strain isolated from lakeside soil.

A Gram-stain-positive, facultatively anaerobic, rod-shaped bacterium, designated JX-17T, was isolated from a soil sample collected in Jiangxi Province, PR China. Growth was observed at 15-48 °C (optimum 37 °C), at pH 5.0-9.0 (optimum pH 7.0) and with 0-6.0% (w/v) NaCl (optimum 1.0%). Strain JX-17T could degrade approximately 50% of 50 mg/L mesotrione within 2 days of incubation, but could not use mesotrione as sole carbon source for growth. Strain JX-17T showed less than 95.3% 16S rRNA gene sequence similarity with type strains of the genus Paenibacillus. In the phylogenetic tree based on 16S rRNA gene and genome sequences, strain JX-17T formed a distinct lineage within the genus Paenibacillus. The ANI values between JX-17T and the most closely related type strains P. lentus CMG1240T and P. farraposensis UY79T were 70.1% and 71.4%, respectively, and the dDDH values between them were 19.0% and 23.3%, respectively. The major cellular fatty acids were anteiso-C15:0, iso-C16:0, anteiso-C17:0 and C16:0, the predominant respiratory quinone was MK-7, the major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, an unidentified glycolipid, an aminophospholipid and a phosphatidylinositol. The diagnostic diamino acid of the peptidoglycan was meso-diaminopimelic acid, and the DNA G + C content was 50.1 mol%. Based on the phylogenetic, phenotypic and chemotaxonomic characteristics, strain JX-17T represents a novel species within the genus Paenibacillus, for which the name Paenibacillus lacisoli sp. nov is proposed, with strain JX-17T (= GDMCC 1.3962T = KCTC 43568T) as the type strain.

Nocardioides jiangxiensis sp. nov., a novel actinobacterium isolated from lakeside soil, exhibiting the biosynthesis potential of mycofactocin.

A Gram-stain-positive, rod-shaped, non-spore-forming and non-motile bacterium, designated WY-20T, was isolated from a lakeside soil sample collected in Jiangxi Province, PR China. Growth was observed at 20-42 °C (optimum 30 °C), pH 5.0-8.0 (optimum pH 7.0) and salinity of 0-3.0% (w/v; optimum 0.5%). Phylogenetic analysis based on the 16S rRNA gene sequences indicated that strain WY-20T belongs to the genus Nocardioides and showed the highest sequence similarity (98.1%) to N. phosphati WYH11-7T, followed by N. cavernaquae K1W22B-1T (97.8%), N. marmoriterrae JOS5-1T (97.2%) and N. jensenii NBRC 14755T (97.1%). The average nucleotide identity and digital DNA-DNA hybridization values between strains WY-20T and N. phosphati WYH11-7T were 83.5% and 26.2%, respectively. The predominant fatty acids (≥ 10% of the total fatty acids) were C18:1ω9c, C17:0, C16:0, summed feature 8 (C18:1ω7c and/or C18: 1ω6c) and C17:1ω9c. The major menaquinone was MK-8 (H4). The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and two unidentified phospholipids. In addition, meso-diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan. Based on phenotypic, genotypic and phylogenetic pieces of evidence, strain WY-20T represents a novel species in the genus Nocardioides, for which the name Nocardioides jiangxiensis sp. nov. is proposed. The type strain is WY-20T (= GDMCC 4.317T = KACC 23379T).

Enhanced Fourier-Hilbert-transform suppression for saturation-induced phase error in phase-shifting profilometry.

Intensity saturation tends to induce severe errors in high dynamic range three-dimensional measurements using structured-light techniques. This paper presents an enhanced Fourier-Hilbert-transform (EFHT) method to suppress the saturation-induced phase error in phase-shifting profilometry, by considering three types of residual errors: nonuniform-reflectivity error, phase-shift error, and fringe-edge error. Background normalization is first applied to the saturated fringe patterns to suppress the effect of the nonuniform reflectivity. A self-correction method is proposed to correct the large phase-shift error in the compensated phase. The self-corrected phase error is detected to assist in locating the fringe-edge area, within which the true phase is computed based on the sub-period phase error model. Experimental results demonstrated the effectiveness of the proposed method in suppressing the saturation-induced phase error and other three types of residual errors with fewer images.

Shiella aurantiaca gen. nov., sp. nov., a novel bacterium isolated from activated sludge, and proposal of Shiellaceae fam. nov.

A novel Gram-stain-negative, long rod-shaped, aerobic, non-motile, non-spore-forming and orange-pigmented bacterium, designated LB-30T, was isolated from activated sludge. Growth was observed at 15-40 °C (optimum 30 °C), pH 6.0-9.0 (optimum 7.0) and salinities of 0-3.0 % (w/v; optimum 2.0 %). LB-30T showed less than 89.9 % sequence similarities to the recognized taxa of the order Cytophagales. The results of phylogenetic analysis based on 16S rRNA gene sequences and phylogenomic tree indicated that LB-30T formed a distinct lineage within the order Cytophagales. The average amino acid identity (AAI) values between LB-30T and members of the related families Cyclobacteriaceae, Fulvivirgaceae, Roseivirgaceae, Reichenbachiellaceae, Cesiribacteraceae, Cytophagaceae and Hymenobacteraceae in the order Cytophagales were 50.5-54.6 %. The sole respiratory quinone of LB-31T was menaquinone 7 (MK-7). The major polar lipids were phosphatidylethanolamine, aminolipid and four unidentified lipids. The major fatty acids were iso-C15 : 0, iso-C15 : 1G and iso-C17 : 0 3-OH. The DNA G+C content was 43.8 mol%, calculated from the genome sequence. On the basis of differences in the phenotypic, physiological and biochemical characteristics, and distinct phylogenetic relationships, strain LB-30T is proposed to represent a novel species in a novel genus for which the name Shiella aurantiaca gen. nov., sp. nov is proposed, within a novel family Shiellaceae fam. nov. of the order Cytophagales. The type strain is LB-30T (=GDMCC 1.3629T= KCTC 92689T).

Toxic effects of combined exposure to cadmium and nitrate on intestinal morphology, immune response, and microbiota in juvenile Japanese flounder (Paralichthys olivaceus).

Cadmium (Cd2+) and nitrate (NO3-) are important environmental pollutants in the offshore marine ecological environment. However, limited research has explored their combined effects, particularly regarding their impact on the microbiota and intestinal health of marine fish. In this study, juvenile Japanese flounders (P. olivaceus) were immersed in seawater samples with different combinations of Cd2+ (0, 0.2, and 2 mg/L) and NO3- (0 and 80 mg/L NO3N) for 30 days to explore their toxic impacts on intestinal morphology, tight junction (TJ) barrier, immune response, and microbiota. Our results showed that Cd2+ or NO3- exposure alone led to histopathological damage of the gut, while their co-exposure aggravated intestinal damage. Moreover, co-exposure substantially decreased TJ-related gene expression, including occludin, claudin-10, and ZO-2, suggesting increased TJ permeability in the gut. Regarding the immune response, we observed upregulated expression of immune-related markers such as HSP40, IL-1ß, TNF-α, and MT, suggesting the onset of intestinal inflammation. Furthermore, Cd2+ and NO3- exposure led to changes in intestinal microflora, characterized by decreased the abundance of Sediminibacterium and NS3a_marine_group while increasing the prevalence of pathogens or opportunistic pathogens such as Ralstonia, Proteus, and Staphylococcus. This alteration in microbiota composition increased network complexity and α-diversity, ultimately causing dysbiosis in the fish gut. Additionally, combined exposure resulted in metabolic disorders that affected the predicted functions of the intestinal microbiota. Overall, our study demonstrates that Cd2+-NO3- co-exposure amplifies the deleterious effects compared to single exposure. These findings enhance our understanding of the ecological risks posed by Cd2+-NO3- co-exposure in marine ecosystems.

Saturation-Induced Phase Error Compensation Method Using Complementary Phase.

Intensity saturation can induce phase error and, thus, measurement error in fringe projection profilometry. To reduce saturation-induced phase errors, a compensation method is developed. The mathematical model of saturation-induced phase errors is analyzed for N-step phase-shifting profilometry, and the phase error is approximately N-folder of the frequency of the projected fringe. Additional N-step phase-shifting fringe patterns with initial phase-shift π/N are projected for generating a complementary phase map. The final phase map is obtained by averaging the original phase map extracted from the original fringe patterns and the complementary phase map, and then the phase error can be canceled out. Both simulations and experiments demonstrated that the proposed method can substantially reduce the saturation-induced phase error and realize accurate measurements for a highly dynamic range of scenarios.

Celastrol-loaded biomimetic nanodrug ameliorates APAP-induced liver injury through modulating macrophage polarization.

Drug-induced liver injury (DILI) is a major concern in clinical treatment as well as postmarketing surveillance, showing an urgent requirement for the development of protective medications. Celastrol (Cel), a highly active natural product extracted from the roots of Tripterygium wilfordii, has a potential liver protective activity due to its antioxidant and anti-inflammatory effects. However, the further application of Cel to DILI remains a challenge because of its short half-life, low solubility, and toxic side effects. Herein, we developed a Cel-loaded biomimetic nanodrug based on erythrocyte membrane vesicles (EMV) for protecting the liver from acetaminophen (APAP)-induced liver injury. The Cel-loaded EMV (C-EMV) with lower cytotoxicity had a well-sustained release effect and exhibited excellent ability for liver accumulation under physiological and pathological conditions. By suppressing the inflammatory response of pro-inflammatory macrophage M1 polarization while stimulating anti-inflammatory macrophage M2 polarization, C-EMV could significantly alleviate the primary pathological manifestations related to liver injury, including aberrant elevation of biochemical indicators, histopathological alterations, neutrophil infiltration as well as hepatocyte DNA fragmentation. The macrophage depletion experiment further demonstrated that the protective effect of C-EMV on APAP-induced liver injury appeared to be dependent on hepatic macrophages. Therefore, C-EMV as a biomimetic nanodrug exhibits great potential for attenuating the progress of DILI, providing a new approach to protecting the liver from DILI as well as other liver inflammatory diseases through a targeted nanodelivery system. KEY MESSAGES: EMV biomimetic nanocarrier has good monodispersity and sustained-release property. EMV biomimetic nanocarrier displays excellent liver-targeting capability under physiological and pathological conditions. C-EMV biomimetic nanodrug with lower cytotoxicity regulates macrophage polarization in vitro and in vivo. C-EMV biomimetic nanodrug can significantly alleviate APAP-induced liver injury. The protective effect of C-EMV on APAP-induced liver injury is dependent on hepatic macrophages.

Sphingomonas caeni sp. nov., a phenolic acid-degrading bacterium isolated from activated sludge.

A Gram-stain-negative, rod-shaped, polar flagellated or stalked and non-spore-forming bacterium, designated LB-2T, was isolated from activated sludge. Growth was observed at 20-30 °C (optimum 28 °C), pH 6.0-8.0 (optimum pH 7.0) and salinity of 0-0.5% (w/v; optimum 0.5%). Phylogenetic analysis based on the 16S rRNA gene indicated that strain LB-2T belongs to the genus Sphingomonas and showed the highest sequence similarity (96.7%) and less than 96.7% similarities to other type strains. The genome size of strain LB-2T was 4.10 Mb, with 66.8 mol% G + C content. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strains LB-2T and S. canadensis FWC47T were 77.8% and 21%, respectively. The predominant cellular fatty acids were summed feature 8 (C18:1ω7c and/or C18 : 1ω6c) and C16:0. The major polar lipids were aminolipid, glycolipid, sphingoglycolipid, phosphatidylcholine, phosphatidylglycerol, four unidentified lipids, glycophospholipid, phosphatidylethanolamine and diphosphatidylglycerol. The predominant respiratory quinone was Q-10 and the major polyamine was sym-homospermidine. On the basis of phenotypic, genotypic and phylogenetic evidences, strain LB-2T represents a novel species in the genus Sphingomonas, for which the name Sphingomonas caeni sp. nov. is proposed. The type strain is LB-2T (GDMCC 1.3630T = NBRC 115,102T).

Single-Shot Multi-Frequency 3D Shape Measurement for Discontinuous Surface Object Based on Deep Learning.

It is challenging to stably and rapidly achieve accurate absolute phase retrieval for isolated objects with a single-shot pattern in fringe projection profilometry (FPP). In this context, a single-shot multi-frequency absolute phase retrieval (SAPR-DL) method based on deep learning is proposed, which only needs to capture one fringe image to obtain the full-field precise absolute phase. Specifically, a low-frequency deformed fringe image is loaded into the trained one-to-two deep learning framework (DLFT) to predict unit-frequency and high-frequency deformed fringe images. Then, three fringe images with different frequencies are loaded into the trained deep learning phase retrieval framework (DLPR) to calculate the corresponding absolute phase. The experimental results prove that the proposed SAPR-DL method can obtain the three-dimensional (3D) shape measurement of multiple complex objects by collecting a single-shot fringe image, showing great prospects in advancing scientific and engineering applications.

Peptide-anchored neutrophil membrane-coated biomimetic nanodrug for targeted treatment of rheumatoid arthritis.

Macrophage polarization determines the production of cytokines that fuel the initiation and evolution of rheumatoid arthritis (RA). Thus, modulation of macrophage polarization might represent a potential therapeutic strategy for RA. However, coordinated modulation of macrophages in the synovium and synovial fluid has not been achieved thus far. Herein, we develop a biomimetic ApoA-I mimetic peptide-modified neutrophil membrane-wrapped F127 polymer (R4F-NM@F127) for targeted drug delivery during RA treatment. Due to the high expression of adhesion molecules and chemokine receptors on neutrophils, the neutrophil membrane coating can endow the nanocarrier with synovitis-targeting ability, with subsequent recruitment to the synovial fluid under the chemotactic effects of IL-8. Moreover, R4F peptide modification further endows the nanocarrier with the ability to target the SR-B1 receptor, which is highly expressed on macrophages in the synovium and synovial fluid. Long-term in vivo imaging shows that R4F-NM@F127 preferentially accumulates in inflamed joints and is engulfed by macrophages. After loading of the anti-inflammatory drug celastrol (Cel), R4F-NM@F127-Cel shows a significant reduction in hepatotoxicity, and effectively inhibits synovial inflammation and alleviates joint damage by reprogramming macrophage polarization. Thus, our results highlight the potential of the coordinated targeted modulation of macrophages as a promising therapeutic option for the treatment of RA.

Corrigendum: A Chinese medicine formula (kunbixiao granule) for female rheumatoid arthritis: Study protocol for a double-blind, randomized, placebo-controlled trial.

[This corrects the article DOI: 10.3389/fphar.2022.945565.].

A chinese medicine formula (kunbixiao granule) for female rheumatoid arthritis: Study protocol for a double-blind, randomized, placebo-controlled trial.

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting females more than males. Clinical symptoms, disease activity and comorbidities are more severe in females. Moreover, the choice of treatment for females is limited during childbearing age due to the side effects of current drugs. Therefore, developing novel and safer drugs for females is urgently needed. Kunbixiao granules (KBXG), a Chinese medicine formula, has been applied to treat female RA patients in our center as a complementary therapy. However, there is insufficient evidence for its effect. Therefore, we aim to conduct a randomized, controlled, double-blind clinical trial to confirm the efficacy and safety of KBXG for the treatment of female RA. Methods: This study is a single-center, double-blind, randomized, parallel group, placebo-controlled clinical trial. A total of 90 female RA patients with Disease Activity Score for 28 joints (DAS28) > 3.2 will be enrolled. They will be randomly assigned to receive either KBXG or placebo for 12 weeks. The change in DAS28 based on C-reactive protein (DAS28-CRP) and the Clinical Disease Activity Index (CDAI) are the primary outcomes. The secondary outcomes include a rate of achieving 20%, 50% and 70% improvement in the American College Rheumatology criteria (ACR20, ACR50, ACR70), TCM syndrome score, visual analogue scale (VAS), average hands grip strength, the consumption of concomitant medication, Hospital Anxiety and Depression Scale (HADS), lumbar spine bone mineral density (L-BMD) and 7-joint ultrasound score (US7). Any adverse events will also be recorded. Discussion: This trial will provide evidence of KBXG in reducing disease activity, and improving clinical symptoms and quality of life of female RA patients. The long-term effects of KBXG on female RA patients still needs a further follow-up.

The comparison of curcuminoid formulations or its combination with conventional therapies versus conventional therapies alone for knee osteoarthritis.

BACKGROUND: Presently, curcuminoid formulations or its combination with conventional therapies has been used for the treatment of knee osteoarthritis (KOA). Nevertheless, evidence is limited due to small-sized clinical trials. This study aims to evaluate the efficacy of curcuminoid formulations or its combination with conventional therapies for KOA. METHODS: Randomized controlled trials comparing curcuminoid formulations or its combination with conventional therapies versus conventional therapies, such as non-steroidal antiinflammatory drugs (NSAIDs) and chondroitin sulfate/glucosamine, were searched from databases. RESULTS: In total, 14 studies involving 1533 patients were included. Curcuminoid formulations were comparative to NSAIDs in reducing Visual Analogue Scale (VAS), total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and WOMAC score for pain/stiffness/physical function. No significant difference was seen between the two groups in terms of patients' satisfaction index, patients' global assessment, reduction of several inflammatory factor, rate of drug compliance, and rescue medication. Notably, curcuminoid formulations combined with NSAIDs significantly reduced VAS and WOMAC/Knee injury and OA Outcome Score (KOOS) pain score more than NSAIDs did. In addition, the curcuminoid formulations were superior to chondroitin sulfate/glucosamine in reducing VAS, total WOMAC score, and WOMAC score for stiffness/difficulty in physical function, while no significant difference was seen in reducing WOMAC pain score and Karnofsky Performance Scale score. CONCLUSIONS: Curcuminoid formulations may be considered a promising alternative for treating KOA. Key points • Curcuminoid formulations are comparative to NSAIDs for KOA. • Curcuminoid formulations are superior to chondroitin sulfate/glucosamine for KOA. • Curcuminoid formulations could provide additional benefits in alleviating pain and some adverse events caused by NSAIDs.

Improved transfer efficiency of supercharged 36 + GFP protein mediate nucleic acid delivery.

The potential of nucleic acid therapeutics to treat diseases by targeting specific cells has resulted in its increasing number of uses in clinical settings. However, the major challenge is to deliver bio-macromolecules into target cells and/or subcellular locations of interest ahead in the development of delivery systems. Although, supercharged residues replaced protein 36 + GFP can facilitate itself and cargoes delivery, its efficiency is still limited. Therefore, we combined our recent progress to further improve 36 + GFP based delivery efficiency. We found that the penetration efficacy of 36 + GFP protein was significantly improved by fusion with CPP-Dot1l or treatment with penetration enhancer dimethyl sulfoxide (DMSO) in vitro. After safely packaged with plasmid DNA, we found that the efficacy of in vitro and in vivo transfection mediated by 36 + GFP-Dot1l fusion protein is also significantly improved than 36 + GFP itself. Our findings illustrated that fusion with CPP-Dot1l or incubation with DMSO is an alternative way to synergically promote 36 + GFP mediated plasmid DNA delivery in vitro and in vivo.

Emerging landscape of cell-penetrating peptide-mediated nucleic acid delivery and their utility in imaging, gene-editing, and RNA-sequencing.

The safety issues like immunogenicity and unacceptable cancer risk of viral vectors for DNA/mRNA vaccine delivery necessitate the development of non-viral vectors with no toxicity. Among the non-viral strategies, cell-penetrating peptides (CPPs) have been a topic of interest recently because of their ability to cross plasma membranes and facilitate nucleic acids delivery both in vivo and in vitro. In addition to the application in the field of gene vaccine and gene therapy, CPPs based nucleic acids delivery have been proved by its potential application like gene editing, RNA-sequencing, and imaging. Here, we focus on summarizing the recent applications and progress of CPPs-mediated nucleic acids delivery and discuss the current problems and solutions in this field.

Platelet-rich fibrin and concentrated growth factors as novel platelet concentrates for chronic hard-to-heal skin ulcers: a systematic review and Meta-analysis of randomized controlled trials.

BACKGROUND: This study aimed to determine superior outcomes of platelet-rich fibrin and concentrated growth factors dressings in chronic hard-to-heal skin ulcers. METHODS: A search in PubMed, EMBASE, Cochrane Library and CINAHL(EBSCO) was performed for randomized controlled trials comparing platelet-rich fibrin or concentrated growth factors dressings to standard wound care in chronic hard-to-heal skin ulcers. Primary outcome was the number of ulcers completely healed. Secondary outcomes were percentage of ulcers area reduction and complications. Dichotomous and continuous results were pooled in risk difference and mean difference respectively, with a 95% confidence interval (CI). RESULTS: Eight studies with 578 patients were included. The number of ulcers completely healed in platelet-rich fibrin was significantly higher than in control group, during the fourth week of follow-up (risk difference, 0.48; 95% CI, 0.31-0.66; p < .00001) and at the end of follow-up (risk difference, 0.17; 95% CI, 0.08-0.26; p = .0003). The pooled result between concentrated growth factors and control group was inconclusive due to two few studies included. CONCLUSIONS: Platelet-rich fibrin is safe and promising to promote healing of chronic hard-to-heal skin ulcers versus standard wound care. Further studies are warranted to evaluate the roles of concentrated growth factors.

The effect of platelet-rich plasma injection on chronic Achilles tendinopathy and acute Achilles tendon rupture.

Several clinical trials exploring the effect of platelet-rich plasma (PRP) on Achilles tendon rupture (ATR) or Achilles tendinopathy (AT) have been published. However, current evidence is limited to small-sized trials. This study aims to evaluate whether PRP improves the outcomes of ATR or AT. PubMed, Web of Science, EMBASE, and Cochrane Library databases were searched to identify randomized controlled trials comparing PRP injection versus placebo for ATR or AT. Eleven studies with 574 patients were included. Quantitative synthesis suggested that compared with placebo, AT patients in PRP group had higher VISA-A score improvement at six-week follow-up (mean difference (MD) = 2.64; 95% CI) = 1.12 to 4.15). However, there was no significant difference between two groups for VISA-A score improvement at three-month follow-up (MD = 0.93; 95% CI = -2.75 to 4.62), or 6-month follow-up (MD = 5.46; 95% CI = -1.19 to 12.11). In ATR patients, quantitative synthesis suggested that no significant difference was seen between PRP and control group at 3-month, 6-month, and 1-year follow-up. In addition, no significant difference was detected between the two groups in improving tendon thickness and pain for AT patients, and no significant difference was seen in improving heel-rise work, maximum heel-rise height, dorsal and plantar flexion, rate of returning to sports activities, and complication for ATR patients. To conclude, no evidence indicates that PRP injection can improve the patient-reported/clinical/functional outcomes of AT or ATR. The increasing times of PRP injection could improve the outcomes, and further clinical randomized controlled trials are expected to be conducted to verify this hypothesis.

Fractional Carbon Dioxide Laser or Erbium:Yttrium-Aluminum-Garnet Laser Assisted by Topical Application/Intradermal Injection of Platelet-Rich Plasma for Postacne Scars.

BACKGROUND: Fractional carbon dioxide or erbium:yttrium-aluminum-garnet (YAG) laser combined with platelet-rich plasma has been used for postacne scars. Nevertheless, there is limited evidence on its use because of the small size of relevant studies. This study aims to evaluate the efficacy of platelet-rich plasma-assisted laser for postacne scars. METHODS: Randomized controlled trials comparing carbon dioxide or erbium:YAG laser combined with platelet-rich plasma to laser alone were searched for using the PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar databases. RESULTS: In total, 13 studies involving 672 cases were included. The overall degree of clinical improvement favored platelet-rich plasma combined with carbon dioxide laser (mean difference, 0.55; 95 percent CI, 0.40 to 0.70) or erbium:YAG laser (mean difference, 0.63; 95 percent CI, 0.31 to 0.96). Notably, the use of carbon dioxide laser combined with platelet-rich plasma was more effective in both greater than 50 percent improvement of acne scars (OR, 1.63; 95 percent CI, 1.10 to 2.42) and greater than 75 percent improvement of acne scars (OR, 2.78; 95 percent CI, 1.75 to 4.42), compared with laser alone. Erbium:YAG laser combined with platelet-rich plasma was more effective in greater than 75 percent improvement of acne scars compared with laser alone (OR, 3.45; 95 percent CI, 1.31 to 9.05). Moreover, patient satisfaction was significantly higher with platelet-rich plasma combined with carbon dioxide laser (OR, 2.98; 95 percent CI, 1.72 to 5.16) or erbium:YAG laser (OR, 2.88; 95 percent CI, 1.33 to 6.21) compared to laser alone. CONCLUSION: This meta-analysis provides reliable evidence that fractional carbon dioxide or erbium:YAG laser combined with platelet-rich plasma is an effective and safe combination therapy for postacne scars. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.