Bio-inspired interfacial chemistry for the fabrication of a robust and functional graphene oxide composite film.

A strong and functional artificial nacre film is developed by using polyethyleneimine-functionalized GO (PEI-GO) and pyrogallol (PG) inspired by insect exoskeleton sclerotization. PEI-GO is macroscopically assembled into the laminated films and then reacted with PG under the optimized condition for their efficient cross-linking through Schiff-base reactions. The internal structure and physicochemical properties of PG-treated PEI-GO (PG@PEI-GO) films are systematically explored with various analytical tools. The optimized PG@PEI-GO films exhibit excellent tensile strength, modulus, and toughness of 216.0 ± 12.9 MPa, 17.0 ± 1.1 GPa, and 2192 ± 538.5 kJ m-3 which are 2.7, 2.8, and 2.3-fold higher than those of GO films, respectively. Furthermore, silver nanoparticles (AgNPs) are densely immobilized on the PG@PEI-GO films harnessing their abundant amine groups, and the AgNPs immobilized PG@PEI-GO films exhibit a high catalytic activity in the conversion of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) with maintaining structural integrity. Based on the results, we demonstrate that the rational design of interfaces, inspired by natural materials, is an efficient approach to achieving strong and functional GO laminated composite films.

Protective effect of the mixture of Lactiplantibacillus plantarum KC3 and Leonurus Japonicas Houtt extract on respiratory disorders.

Air pollutants, such as particulate matter (PM) and diesel exhaust particles (DEP), are associated with respiratory diseases. Therefore, preventive and therapeutic strategies against PM-and DEP (PM10D)-induced respiratory diseases are needed. Herein, we evaluate the protective effects of a mixture of Lactiplantibacillus plantarum KC3 and Leonurus Japonicas Houtt (LJH) extract against airway inflammation associated with exposure to PM10D. To determine the anti-inflammatory effects of the LJH extract, reactive oxygen species (ROS) production and the expression of inflammatory pathways were determined in PM10-induced MH-S cells. For the respiratory protective effects, BALB/c mice were exposed to PM10D via intranasal injection, and a mixture of L. plantarum KC3 and LJH extract was administered orally for 12 days. LJH extract inhibited ROS production and the phosphorylation of downstream factors of NF-κB in PM10-stimulated MH-S cells. The mixture of L. plantarum KC3 and LJH repressed the infiltration of neutrophils, reduced the immune cells number, and suppressed the proinflammatory mediators and cyclooxygenase (COX)-2 expressions in PM10D-induced airway inflammation with reduced phosphorylation of downstream factors of NF-κB. In addition, these effects were not observed in an alveolar macrophage depleted PM10D-induced mouse model using clodronate liposomes. The extract mixture also regulated gut microbiota in feces and upregulated the mRNA expression of Foxp3, transforming growth factor (TGF)-ß1, and interleukin (IL)-10 in the colon. The L. plantarum KC3 and LJH extract mixture may inhibit alveolar macrophage- and neutrophil-mediated inflammatory responses and regulate gut microbiota and immune response in PM10D-induced airway inflammation, suggesting it is a potential remedy to prevent and cure airway inflammation and respiratory disorders.

The maintenance mechanism of hematopoietic stem cell dormancy: role for a subset of macrophages.

Hematopoiesis is regulated by crosstalk between long-term repopulating hematopoietic stem cells (LT-HSCs) and supporting niche cells in the bone marrow (BM). Here, we describe the role of KAI1, which is mainly expressed on LT-HSCs and rarely on other hematopoietic stem-progenitor cells (HSPCs), in nichemediated LT-HSC maintenance. KAI1 activates TGF-ß1/Smad3 signal in LT-HSCs, leading to the induction of CDK inhibitors and inhibition of the cell cycle. The KAI1-binding partner DARC is expressed on macrophages and stabilizes KAI1 on LT-HSCs, promoting their quiescence. Conversely, when DARC+ BM macrophages were absent, the level of surface KAI1 on LT-HSCs decreases, leading to cell-cycle entry, proliferation, and differentiation. Thus, KAI1 acts as a functional surface marker of LTHSCs that regulates dormancy through interaction with DARCexpressing macrophages in the BM stem cell niche. Recently, we showed very special and rare macrophages expressing α-SMA+ COX2+ & DARC+ induce not only dormancy of LTHSC through interaction of KAI1-DARC but also protect HSCs by down-regulating ROS through COX2 signaling. In the near future, the strategy to combine KAI1-positive LT-HSCs and α-SMA/Cox2/DARC triple-positive macrophages will improve the efficacy of stem cell transplantation after the ablative chemo-therapy for hematological disorders including leukemia. [BMB Reports 2023; 56(9): 482-487].

Arthroscopic Implantation of Adipose-Derived Stromal Vascular Fraction Improves Cartilage Regeneration and Pain Relief in Patients With Knee Osteoarthritis.

Purpose: To compare the pain relief and cartilage repair status of patients with knee osteoarthritis who received arthroscopic treatment with or without stromal vascular fraction (SVF) implantation. Methods: We retrospectively evaluated the patients who were examined with 12-month follow-up magnetic resonance imaging (MRI) after arthroscopic treatment for knee osteoarthritis from September 2019 to April 2021. Patients were included in this study if they had grade 3 or 4 knee osteoarthritis according to the Outerbridge classification in MRI. The visual analog scale (VAS) was used for pain assessment over the follow-up period (baseline and at 1-, 3-, 6-, and 12-month follow-ups). Cartilage repair was evaluated using follow-up MRIs based on Outerbridge grades and the Magnetic Resonance Observation of Cartilage Repair Tissue scoring system. Results: Among 97 patients who received arthroscopic treatment, 54 patients received arthroscopic treatment alone (conventional group) and 43 received arthroscopic treatment along with SVF implantation (SVF group). In the conventional group, the mean VAS score decreased significantly at 1-month post-treatment compared with baseline (P < .05), and gradually increased from 3 to 12 months' post-treatment (all P < .05). In the SVF group, the mean VAS score decreased until 12 months post-treatment compared with baseline (all P < .05 except P = .780 in 1-month vs 3-month follow-ups). Significantly greater pain relief was reported in the SVF group than in the conventional group at 6 and 12 months' post-treatment (all P < .05). Overall, Outerbridge grades were significantly greater in the SVF group than in the conventional group (P < .001). Similarly, mean Magnetic Resonance Observation of Cartilage Repair Tissue scores were significantly greater (P < .001) in the SVF group (70.5 ± 11.1) than in the conventional group (39.7 ± 8.2). Conclusions: The results regarding pain improvement and cartilage regeneration and the significant correlation between pain and MRI outcomes at 12-months follow-up indicate that the arthroscopic SVF implantation technique may be useful for repairing cartilage lesions in knee osteoarthritis. Level of Evidence: Level III, retrospective comparative study.

Adipose-Derived Stromal Vascular Fractions Are Comparable With Allogenic Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells as a Supplementary Strategy of High Tibial Osteotomy for Varus Knee Osteoarthritis.

Purpose: To compare the clinical, radiologic, and second-look arthroscopic outcomes of high tibial osteotomy (HTO) with stromal vascular fraction (SVF) implantation versus human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSC) transplantation and identify the association between cartilage regeneration and HTO outcomes. Methods: Patients treated with HTO for varus knee osteoarthritis between March 2018 and September 2020 were retrospectively identified. In this retrospective study, among 183 patients treated with HTO for varus knee osteoarthritis between March 2018 and September 2020, patients treated with HTO with SVF implantation (SVF group; n = 25) were pair-matched based on sex, age, and lesion size with those who underwent HTO with hUCB-MSC transplantation (hUCB-MSC group; n = 25). Clinical outcomes were evaluated using the International Knee Documentation Committee score and Knee Injury and Osteoarthritis Outcome Score. Radiological outcomes evaluated were the femorotibial angle and posterior tibial slope. All patients were evaluated clinically and radiologically before surgery and during follow-up. The mean final follow-up periods were 27.8 ± 3.6 (range 24-36) in the SVF group and 28.2 ± 4.1 (range, 24-36) in the hUCB-MSC group (P = 0.690). At second-look arthroscopic surgery, cartilage regeneration was evaluated using the International Cartilage Repair Society (ICRS) grade. Results: A total of 17 male and 33 female patients with a mean age of 56.2 years (range, 49-67 years) were included. At the time of second-look arthroscopic surgery (mean, 12.6 months; range, 11-15 months in the SVF group and 12.7 months; range, 11-14 months in the hUCB-MSC group, P = .625), the mean International Knee Documentation Committee score and Knee Injury and Osteoarthritis Outcome Score in each group significantly improved (P < .001 for all), and clinical outcomes at final follow-up further improved in both groups when compared with the values at second-look arthroscopic surgery (P < .05 for all). Overall ICRS grades, which significantly correlated with clinical outcomes, were similar between groups with no significant differences (P = .170 for femoral condyle and P = .442 for tibial plateau). Radiologic outcomes at final follow-up showed improved knee joint alignment relative to preoperative conditions but showed no significant correlation with clinical outcomes or ICRS grade in either group (P > .05 for all). Conclusions: Improved clinical and radiological outcomes and favorable cartilage regeneration were seen after surgery for varus Knee OA in both SVF and hUCB-MSC groups. Level of Evidence: Level III, retrospective comparative study.

Protective Effect of Novel Lactobacillus plantarum KC3 Isolated from Fermented Kimchi on Gut and Respiratory Disorders.

Probiotics have been shown to possess anti-inflammatory effects in the gut by directly reducing the production of pro-inflammatory cytokines and by secreting anti-inflammatory molecules. However, their systemic anti-inflammatory effects have not been thoroughly investigated. In this study, we aimed to develop probiotics that have efficacy in both intestinal and lung inflammation. Lactobacillus plantarum KC3 (KC3), which was isolated from kimchi, was selected as a pre-candidate based on its inhibitory effects on the production of pro-inflammatory cytokines in vitro. To further validate the effectiveness of KC3, we used ear edema, DSS-induced colitis, and ambient particulate-matter-induced lung inflammation models. First, KC3 exhibited direct anti-inflammatory effects on intestinal cells with the inhibition of IL-1ß and TNF-α production. Additionally, KC3 treatment alleviated ear edema and DSS-induced colic inflammation, improving colon length and increasing the number of regulatory T cells. Beyond its local intestinal anti-inflammatory activity, KC3 inhibited pro-inflammatory cytokines in the bronchoalveolar fluid and prevented neutrophil infiltration in the lungs. These results suggest that KC3 could be a potential functional ingredient with respiratory protective effects against air-pollutant-derived inflammation, as well as for the treatment of local gut disorders.

Cartilage lesion size and number of stromal vascular fraction (SVF) cells strongly influenced the SVF implantation outcomes in patients with knee osteoarthritis.

PURPOSE: This study evaluated outcomes in patients with knee osteoarthritis following stromal vascular fraction implantation and assessed the associated prognostic factors. METHODS: We retrospectively evaluated 43 patients who underwent follow-up magnetic resonance imaging 12 months after stromal vascular fraction implantation for knee osteoarthritis. Pain was assessed using the visual analogue scale and measured at baseline and 1-, 3-, 6-, and 12-month follow-up appointments. In addition, cartilage repair was evaluated based on the Magnetic Resonance Observation of Cartilage Repair Tissue scoring system using the magnetic resonance imaging from the 12-month follow-up. Finally, we evaluated the effects of various factors on outcomes following stromal vascular fraction implantation. RESULTS: Compared to the baseline value, the mean visual analogue scale score significantly and progressively decreased until 12 months post-treatment (P < 0.05 for all, except n.s. between the 1 and 3-month follow-ups). The mean Magnetic Resonance Observation of Cartilage Repair Tissue score was 70.5 ± 11.1. Furthermore, the mean visual analogue scale and Magnetic Resonance Observation of Cartilage Repair Tissue scores significantly correlated 12 months postoperatively (P = 0.002). Additionally, the cartilage lesion size and the number of stromal vascular fraction cells significantly correlated with the 12-month visual analogue scale scores and the Magnetic Resonance Observation of Cartilage Repair Tissue score. Multivariate analyses determined that the cartilage lesion size and the number of stromal vascular fraction cells had a high prognostic significance for unsatisfactory outcomes. CONCLUSION: Stromal vascular fraction implantation improved pain and cartilage regeneration for patients with knee osteoarthritis. The cartilage lesion size and the number of stromal vascular fraction cells significantly influenced the postoperative outcomes. Thus, these findings may serve as a basis for preoperative surgical decisions. LEVEL OF EVIDENCE: IV.

Strategy of Patient-Specific Therapeutics in Cardiovascular Disease Through Single-Cell RNA Sequencing.

Recently, single cell RNA sequencing (scRNA-seq) technology has enabled the discovery of novel or rare subtypes of cells and their characteristics. This technique has advanced unprecedented biomedical research by enabling the profiling and analysis of the transcriptomes of single cells at high resolution and throughput. Thus, scRNA-seq has contributed to recent advances in cardiovascular research by the generation of cell atlases of heart and blood vessels and the elucidation of mechanisms involved in cardiovascular development and diseases. This review summarizes the overall workflow of the scRNA-seq technique itself and key findings in the cardiovascular development and diseases based on the previous studies. In particular, we focused on how the single-cell sequencing technology can be utilized in clinical field and precision medicine to treat specific diseases.

Increased viral load in patients infected with severe acute respiratory syndrome coronavirus 2 Omicron variant in the Republic of Korea

Objectives@#Coronavirus disease 2019 (COVID-19) has been declared a global pandemic owingto the rapid spread of the causative agent, severe acute respiratory syndrome coronavirus 2.Its Delta and Omicron variants are more transmissible and pathogenic than other variants.Some debates have emerged on the mechanism of variants of concern. In the COVID-19 wave that began in December 2021, the Omicron variant, first reported in South Africa, became identifiable in most cases globally. The aim of this study was to provide data to inform effective responses to the transmission of the Omicron variant. @*Methods@#The Delta variant and the spike protein D614G mutant were compared with the Omicron variant. Viral loads from 5 days after symptom onset were compared usingepidemiological data collected at the time of diagnosis. @*Results@#The Omicron variant exhibited a higher viral load than other variants, resulting in greater transmissibility within 5 days of symptom onset. @*Conclusion@#Future research should focus on vaccine efficacy against the Omicron variant and compare trends in disease severity associated with its high viral load.

A subset of macrophages and monocytes in the mouse bone marrow express atypical chemokine receptor 1.

Duffy antigen receptor for chemokines (DARC)/CD234, also known as atypical chemokine receptor 1 (ACKR1), is a seven-transmembrane domain protein expressed on erythrocytes, vascular endothelium, and a subset of epithelial cells (Peiper et al., 1995). Previously, we reported that ACKR1 was expressed in bone marrow macrophages. ACKR1 interacts with CD82 on long-term repopulating hematopoietic stem cells (LT-HSCs) to maintain the dormancy of LT-HSCs during homeostasis (Hur et al., 2016). We also demonstrated that ACKR1 interacts with CD82 in HSCs from human umbilical cord blood (hUCB). These findings demonstrated that CD82 is a functional surface marker of LT-HSCs and this molecule maintains LT-HSC quiescence by interactions with ACKR1-expressing macrophages in mice and humans.

Efficient Protection of Silver Nanowire Transparent Electrodes by All-Biorenewable Layer-by-Layer Assembled Thin Films.

An efficient protection strategy for silver nanowire-based transparent electrodes (AgNW TEs) is developed to enhance their poor adhesion force on substrates and thermal, optical, chemical, and electrical stabilities. Chitin nanofibers (CNFs) and alkali lignin (AL), which possess high mechanical property, a gas/moisture barrier, and UV absorption properties, are successively assembled on AgNW TEs through layer-by-layer (LBL) assembly based on their oppositely charged surfaces. The formation of LBL-assembled CNFs and AL (CNF/AL)10 bilayers, where 10 is the optimized number of bilayers, on the aldehyde-modified AgNW (Al-AgNW) TEs does not deteriorate their electrical conductivity (17.3 ± 2.1 Ω/□) and transmittance (90.1 ± 0.3% at 550 nm), and the (CNF/AL)10 bilayer-coated Al-AgNW [(CNF/AL)10@Al-AgNW] TEs present considerable enhancement in their adhesion force and thermal, optical, chemical, and electrical durability. In detail, their optoelectrical properties are stable over 200 cycles of the scotch peel-off test, for 10 h sonication, up to 350 °C, under UV/O3 treatment for 100 min, in 10% HCl and 28% NH3 for 6 and 12 h, and at an electrical potential up to 14 V, respectively. These features make (CNF/AL)10@Al-AgNW TEs suitable as a durable high-performance transparent heater.

Immunostimulatory Effect of Heat-Killed Probiotics on RAW264.7 Macrophages.

Probiotics modulate the gut microbiota, which in turn regulate immune responses to maintain balanced immune homeostasis in the host. However, it is unclear how probiotic bacteria regulate immune responses. In this study we investigated the immunomodulatory effects of heat-killed probiotics, including Lactiplantibacillus plantarum KC3 (LP3), Lactiplantibacillus plantarum CKDB008 (LP8), and Limosilactobacillus fermentum SRK414 (LF4), via phagocytosis, nitric oxide (NO), and pro-inflammatory cytokine production in macrophages. We thus found that heat-killed LP8 could promote the clearance of foreign pathogens by enhancing the phagocytosis of macrophages. Treatment with heat-killed LP8 induced the production of NO and pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1ß. In addition, heat-killed LP8 suppressed the production of NO and cytokines in LPS-induced RAW264.7 cells, suggesting that heat-killed LP8 exerts immunomodulatory effects depending on the host condition. In sum, these results indicate that heat-killed LP8 possesses the potential for immune modulation while providing a molecular basis for the development of functional probiotics prepared from inactivated bacterial cells.

Lateral Size Effect of Graphene Oxide on Its Surface-Enhanced Raman Scattering Property.

The lateral size effect of graphene oxide (GO) on surfaced-enhanced Raman scattering (SERS) property is systematically investigated by using size-fractionalized GO. For the size fractionalization without changes of chemical structure, large-sized GO (LGO) and small-sized GO (SGO) are separated from the as-synthesized GO (AGO) by centrifugation and membrane filtration, respectively. The size-fractionalized GO sheets are immobilized on a solid substrate for the parallel comparison of their SERS property. As a result, we find that LGO shows considerably higher SERS property than SGO for typical Raman probes such as rhodamine 6G and crystal violet. Furthermore, the lateral size effect of GO derivatives is consistently observed when they are hybridized with plasmonic silver nanoparticles. These results indicate that LGO is superior to AGO and SGO as a SERS platform, and it is also quantitatively confirmed by calculating their enhancement factor.

KAI1(CD82) is a key molecule to control angiogenesis and switch angiogenic milieu to quiescent state.

BACKGROUND: Little is known about endogenous inhibitors of angiogenic growth factors. In this study, we identified a novel endogenous anti-angiogenic factor expressed in pericytes and clarified its underlying mechanism and clinical significance. METHODS: Herein, we found Kai1 knockout mice showed significantly enhanced angiogenesis. Then, we investigated the anti-angiogenic roll of Kai1 in vitro and in vivo. RESULTS: KAI1 was mainly expressed in pericytes rather than in endothelial cells. It localized at the membrane surface after palmitoylation by zDHHC4 enzyme and induced LIF through the Src/p53 pathway. LIF released from pericytes in turn suppressed angiogenic factors in endothelial cells as well as in pericytes themselves, leading to inhibition of angiogenesis. Interestingly, KAI1 had another mechanism to inhibit angiogenesis: It directly bound to VEGF and PDGF and inhibited activation of their receptors. In the two different in vivo cancer models, KAI1 supplementation significantly inhibited tumor angiogenesis and growth. A peptide derived from the large extracellular loop of KAI1 has been shown to have anti-angiogenic effects to block the progression of breast cancer and retinal neovascularization in vivo. CONCLUSIONS: KAI1 from PC is a novel molecular regulator that counterbalances the effect of angiogenic factors.

Safety Assessment of Lactiplantibacillus (formerly Lactobacillus) plantarum Q180.

The safety of the probiotic strain Q180, which exerts postprandial lipid-lowering effects, was bioinformatically and phenotypically evaluated. The genome of strain Q180 was completely sequenced, and single circular chromosome of 3,197,263 bp without any plasmid was generated. Phylogenetic and related analyses using16S rRNA gene and whole-genome sequences revealed that strain Q180 is a member of Lactiplantibacillus (Lp., formerly Lactobacillus) plantarum. Antimicrobial resistance (AMR) genes were bioinformatically analyzed using all Lp. plantarum genomes available in GenBank, which showed that AMR genes are present differently depending on Lp. plantarum strains. Bioinformatic analysis demonstrated that some mobile genetic elements such as prophages and insertion sequences were identified in the genome of strain Q180, but because they did not contain harmful genes such as AMR genes and virulence factor (VF)- and toxin-related genes, it was suggested that there is no transferability of harmful genes. The minimum inhibition concentrations of seven tested antibiotics suggested by the European Food Safety Authority guidelines were slightly lower than or equal to the microbiological cut-off values for Lp. plantarum. Strain Q180 did not show hemolytic and gelatinase activities and biogenic amine-producing ability. Taken together, this study demonstrated the safety of strain Q180 in terms of absence of AMR genes and VF- and toxin-related genes as a probiotic strain.

HLA DR Genome Editing with TALENs in Human iPSCs Produced Immune-Tolerant Dendritic Cells.

Although human induced pluripotent stem cells (iPSCs) can serve as a universal cell source for regenerative medicine, the use of iPSCs in clinical applications is limited by prohibitive costs and prolonged generation time. Moreover, allogeneic iPSC transplantation requires preclusion of mismatches between the donor and recipient human leukocyte antigen (HLA). We, therefore, generated universally compatible immune nonresponsive human iPSCs by gene editing. Transcription activator-like effector nucleases (TALENs) were designed for selective elimination of HLA DR expression. The engineered nucleases completely disrupted the expression of HLA DR on human dermal fibroblast cells (HDF) that did not express HLA DR even after stimulation with IFN-γ. Teratomas formed by HLA DR knockout iPSCs did not express HLA DR, and dendritic cells differentiated from HLA DR knockout iPSCs reduced CD4+ T cell activation. These engineered iPSCs might provide a novel translational approach to treat multiple recipients from a limited number of cell donors.

An antibody against L1 cell adhesion molecule inhibits cardiotoxicity by regulating persistent DNA damage.

Targeting the molecular pathways underlying the cardiotoxicity associated with thoracic irradiation and doxorubicin (Dox) could reduce the morbidity and mortality associated with these anticancer treatments. Here, we find that vascular endothelial cells (ECs) with persistent DNA damage induced by irradiation and Dox treatment exhibit a fibrotic phenotype (endothelial-mesenchymal transition, EndMT) correlating with the colocalization of L1CAM and persistent DNA damage foci. We demonstrate that treatment with the anti-L1CAM antibody Ab417 decreases L1CAM overexpression and nuclear translocation and persistent DNA damage foci. We show that in whole-heart-irradiated mice, EC-specific p53 deletion increases vascular fibrosis and the colocalization of L1CAM and DNA damage foci, while Ab417 attenuates these effects. We also demonstrate that Ab417 prevents cardiac dysfunction-related decrease in fractional shortening and prolongs survival after whole-heart irradiation or Dox treatment. We show that cardiomyopathy patient-derived cardiovascular ECs with persistent DNA damage show upregulated L1CAM and EndMT, indicating clinical applicability of Ab417. We conclude that controlling vascular DNA damage by inhibiting nuclear L1CAM translocation might effectively prevent anticancer therapy-associated cardiotoxicity.

Plant callus-derived shikimic acid regenerates human skin through converting human dermal fibroblasts into multipotent skin-derived precursor cells.

BACKGROUND: The human skin-derived precursors (SKPs) are a good cell source for regeneration. However, the isolation of SKP from human skin is limited. To overcome this drawback, we hypothesized that the component of plant stem cells could convert human fibroblasts to SKPs. METHODS: Human dermal fibroblasts were treated with shikimic acid, a major component of Sequoiadendron giganteum callus extract. The characteristics of these reprogrammed cells were analyzed by qPCR, western blot, colony-forming assay, and immunofluorescence staining. Artificial human skin was used for CO2 laser-induced wound experiments. Human tissues were analyzed by immunohistochemistry. RESULTS: The reprogrammed cells expressed nestin (a neural precursor-specific protein), fibronectin, and vimentin and could differentiate into the ectodermal and mesodermal lineage. Nestin expression was induced by shikimic acid through the mannose receptor and subsequent MYD88 activation, leading to P38 phosphorylation and then CREB binding to the nestin gene promoter. Finally, we confirmed that shikimic acid facilitated the healing of cut injury and enhanced dermal reconstruction in a human artificial skin model. Moreover, in a clinical study with healthy volunteers, plant callus extracts increased the expression of stem cell markers in the basal layer of the epidermis and collagen deposit in the dermis. CONCLUSIONS: These results indicate that shikimic acid is an effective agent for tissue regeneration.

Factors Influencing Clinical and MRI Outcomes of Mesenchymal Stem Cell Implantation With Concomitant High Tibial Osteotomy for Varus Knee Osteoarthritis.

BACKGROUND: Cartilage repair procedures using mesenchymal stem cells (MSCs) can provide superior cartilage regeneration in the medial compartment of the knee joint when high tibial osteotomy (HTO) is performed for varus knee osteoarthritis (OA). However, few studies have reported the factors influencing the outcomes of MSC implantation with concomitant HTO. PURPOSE: To investigate the outcomes of MSC implantation with concomitant HTO and to identify the prognostic factors that are associated with the outcomes. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 71 patients (75 knees) were retrospectively evaluated after MSC implantation with concomitant HTO. Clinical and radiological outcomes were evaluated, and magnetic resonance imaging (MRI) was used to assess cartilage regeneration. Statistical analyses were performed to determine the effect of different factors on clinical, radiographic, and MRI outcomes. RESULTS: Clinical and radiographic outcomes improved significantly from preoperatively to final follow-up (P < .001 for all), and overall cartilage regeneration was encouraging. Significant correlations were found between clinical and MRI outcomes. However, radiographic outcomes were not significantly correlated with clinical or MRI outcomes. Patient age and number of MSCs showed significant correlations with clinical and MRI outcomes. On multivariate analyses, patient age and number of MSCs showed high prognostic significance with poor clinical outcomes. CONCLUSION: MSC implantation with concomitant HTO provided feasible cartilage regeneration and satisfactory clinical outcomes for patients with varus knee OA. Patient age and number of MSCs were important factors that influenced the clinical and MRI outcomes of MSC implantation with concomitant HTO for varus knee OA.