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This study aimed to evaluate the inhibitory effects of micro-current stimulation (MCS) on inflammatory responses in chondrocytes and degradation of extracellular matrix (ECM) in osteoarthritis (OA). To determine the efficacy of MCS, IL-1ß-treated chondrocytes and monosodium iodoacetate (MIA)-induced OA rat model were used. To evaluate the cytotoxicity and nitric oxide (NO) production in SW1353 cells, the presence or absence of IL-1ß treatment or various levels of MCS were applied. Immunoblot analysis was conducted to evaluate whether MCS can modulate IL-1R1/MyD88/NF-κB signaling pathway and various indicators involved in ECM degradation. Additionally, to determine whether MCS alleviates subchondral bone structure destruction caused by OA, micro-CT analysis, immunoblot analysis, and ELISA were conducted using OA rat model. 25 and 50 µA levels of MCS showed effects in cell proliferation and NO production. The MCS group with IL-1ß treatment lead to significant inhibition of protein expression levels regarding IL-1R1/MyD88/NF-κB signaling and reduction of the nucleus translocation of NF-κB. In addition, the protein expression levels of MMP-1, MMP-3, MMP-13, and IL-1ß decreased, whereas collagen II and aggrecan increased. In animal results, morphological analysis of subchondral bone using micro-CT showed that MCS induced subchondral bone regeneration and improvement, as evidenced by increased thickness and bone mineral density of the subchondral bone. Furthermore, MCS-applied groups showed decreases in the protein expression of MMP-1 and MMP-3, while increases in collagen-II and aggrecan expressions. These findings suggest that MCS has the potential to be used as a non-pharmaceutical method to alleviate OA.
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The complete genome of the potential probiotic Lactiplantibacillus plantarum strain beLP1, isolated from kimchi in South Korea, was sequenced using Illumina and PacBio technologies. The genome comprises one circular chromosome and one plasmid without antimicrobial resistance genes.
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BACKGROUND: Uncontrollable and widespread bleeding caused by surgery or sudden accidents can lead to death if not treated with appropriate hemostasis. To prevent excessive life-threatening bleeding, various hemostatic agents based on polymeric biomaterials with various additives for accelerated blood coagulation have been adopted in clinical fields. In particular, platelet-rich plasma (PRP), which contains many blood coagulation factors that can accelerate blood clot formation, is considered as one of the most effective hemostatic additives. METHODS: We investigated a PRP-embedded porous film using discarded (expired) PRP and a film with a leaf-stacked structure (FLSS), as a hemostatic agent to induce rapid hemostasis. The film, which contained an LSS on one side (PCL-FLSS), was fabricated by a simple heating-cooling technique using tetraglycol and polycaprolactone (PCL) film. Activated PRP was obtained by the thawing of frozen PRP at the end of its expiration date (the platelet cell membrane is disrupted during the freezing and thawing of PRP, thus releasing various coagulation factors) and embedded in the PCL-FLSS (PRP-FLSS). RESULTS: From in vitro and in vivo experiments using a rat hepatic bleeding model, it was recognized that PRP-FLSS is not only biocompatible but also significantly accelerates blood clotting and thus prevents rapid bleeding, probably due to a synergistic effect of the sufficient supply of various blood coagulants from activated PRP embedded in the LSS layer and the large surface area of the LSS itself. CONCLUSION: The study suggests that PRP-FLSS, a combination of a porous polymer matrix with a unique morphology and discarded biofunctional resources, can be an advanced hemostatic agent as well as an upcycling platform to avoid the waste of biofunctional resources.
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A composite material of tungsten carbide and mesoporous carbon was synthesized by the sol-gel polycondensation of resorcinol and formaldehyde, using cetyltrimethylammonium bromide as a surfactant and Ludox HS-40 as a porogen, and served as a support for Pd-based electrodes. Phosphorus-modified Pd particles were deposited onto the support using an NH3-mediated polyol reduction method facilitated by sodium hypophosphite. Remarkably small Pd nanoparticles with a diameter of ca. 4 nm were formed by the phosphorus modification. Owing to the high dispersion of Pd and its strong interaction with tungsten carbide, the Pd nanoparticles embedded in the tungsten carbide/mesoporous carbon composite exhibited a hydrogen oxidation activity approximately twice as high as that of the commercial Pt/C catalyst under the anode reaction conditions of proton exchange membrane fuel cells.
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Electrochemical CO2 reduction reaction (eCO2RR) over Cu-based catalysts is a promising approach for efficiently converting CO2 into value-added chemicals and alternative fuels. However, achieving controllable product selectivity from eCO2RR remains challenging because of the difficulty in controlling the oxidation states of Cu against robust structural reconstructions during the eCO2RR. Herein, we report a novel strategy for tuning the oxidation states of Cu species and achieving eCO2RR product selectivity by adjusting the Cu content in CuMgAl-layered double hydroxide (LDH)-based catalysts. In this strategy, the highly stable Cu2+ species in low-Cu-containing LDHs facilitated the strong adsorption of *CO intermediates and further hydrogenation into CH4. Conversely, the mixed Cu0/Cu+ species in high-Cu-containing LDHs derived from the electroreduction during the eCO2RR accelerated C-C coupling reactions. This strategy to regulate Cu oxidation states using LDH nanostructures with low and high Cu molar ratios produced an excellent eCO2RR performance for CH4 and C2+ products, respectively.
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Aminopyrrolnitrin (APRN), a natural halogenated phenylpyrrole derivative (HPD), has strong antifungal and antiparasitic activities. Additionally, it showed 2.8-fold increased photostability compared to pyrrolnitrin, a commercially available HPD with antimicrobial activity. For microbial production of APRN, we first engineered anthranilate phosphoribosyltransferase encoded by trpD from Corynebacterium glutamicum, resulting in a TrpDA162D mutation that exhibits feedback-resistant against L-tryptophan and higher substrate affinity compared to wild-type TrpD. Plasmid-borne expression of trpDA162D in C. glutamicum TP851 strain with two copies of trpDA162D in the genome led to the production of 3.1 g/L L-tryptophan in flask culture. Subsequent step for L-tryptophan chlorination into 7-chloro-L-tryptophan was achieved by introducing diverse sources of genes encoding tryptophan 7-halogenase (PrnA or RebH) and flavin reductase (Fre, PrnF, or RebF). The combined expression of prnA from Serratia grimesii or Serratia plymuthica with flavin reductase gene from Escherichia coli, Pseudomonas fluorescens, or Lechevalieria aerocolonigenes yielded higher production of 7-chloro-L-tryptophan in comparison to other sets of two-component systems. In the next step, production of putative monodechloroaminopyrrolnitrin (MDAP) from 7-chloro-L-tryptophan was achieved through the expression of prnB encoding MDAP synthase from S. plymuthica or P. fluorescens. Finally, an artificial APRN biosynthetic pathway was constructed by simultaneously expressing genes coding for tryptophan 7-halogenase, flavin reductase, MDAP synthase, and MDAP halogenase (PrnC) from different microbial sources within the L-tryptophan-producing TP851 strain. As prnC from S. grimesii or S. plymuthica was introduced into the host strain, which carried plasmids expressing prnA from S. plymuthica, fre from E. coli, and prnB from S. plymuthica, APN3639 and APN3638 accumulated 29.5 mg/L and 28.1 mg/L of APRN in the culture broth. This study represents the first report on the fermentative APRN production by metabolically engineered C. glutamicum.
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Corynebacterium glutamicum , Engenharia Metabólica , Corynebacterium glutamicum/metabolismo , Corynebacterium glutamicum/genética , Engenharia Metabólica/métodos , Pirrolnitrina/biossíntese , Pirrolnitrina/metabolismo , Fermentação , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Triptofano/biossíntese , Triptofano/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , OxirredutasesRESUMO
Background/purpose: The long-term outcomes of implants placed in grafted sinuses using recombinant human bone morphogenetic protein-2 (rhBMP-2) are unclear. This study aimed to compare 3- and 5-year implant survival rates and marginal bone loss (MBL) during functional loading. Materials and methods: In this retrospective study, we analyzed 63 implants inserted after maxillary sinus floor augmentation (MSFA) in 45 patients between January 2016 and April 2019. The outcome variables were: 1) 3- and 5-year cumulative survival rates of the implants and 2) MBL after functional loading. Other assessed variables included patient demographic information, preoperative residual bone height (RBH), surgical site, implant length and diameter, graft material, healing period before loading, prosthetic type, and opposing dentition. Results: The cumulative 3- and 5-year survival rates of the implants were 100% in the rhBMP-2 group and 95.5% and 86.4% in the non-rhBMP-2 group, respectively. The average 3- and 5-year MBL were 1.14 ± 0.67 mm, 1.30 ± 0.74 mm in the rhBMP-2 group and 1.68 ± 0.90 mm, 2.27 ± 1.29 mm in the non-rhBMP-2 group, respectively. Significant differences were observed between 3 and 5 years between the two groups. Conclusion: Addition of the rhBMP-2 to the graft materials positively affects implant placement in the grafted maxillary sinus in terms of implant survival and MBL when preoperative RBH is unfavorable.
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BACKGROUND: Various induction regimens are available for kidney transplantation (KT); however, which is superior remains unclear. Moreover, although the induction regimens are effective and important for reducing side effects, their respective relationships with antibody-mediated rejection (AMR) after transplantation remain unclear. Therefore, this study aimed to elucidate the most effective induction regimen for AMR reduction through network analysis. METHODS: We performed a comprehensive search of databases, including basiliximab, alemtuzumab, antithymocyte globulin (ATG), and daclizumab as induction regimens for KT from inception to September 1, 2022. Using a network meta-analysis, we investigated the priorities of 5 induction regimens for patient survival, graft failure, and graft rejection after ABO-incompatible KT. RESULTS: In total, 25 studies comprising 1768 people were included in this network meta-analysis. The primary outcome was the AMR rate of other induction regimens compared with that of basiliximab, whereas the secondary outcomes were heart failure, stroke, hospitalization, peripheral artery disease, myocardial infarction, anemia, leukopenia, herpes zoster, or adverse events. Notably, ATG reduced the AMR rate by 59% (odds ratio, 0.41; 95% credible interval, 0.20-0.90), whereas the other drugs did not show statistical significance. Furthermore, secondary outcomes did not significantly differ between the induction regimens. CONCLUSION: ATG is widely used in KT induction regimens. Our results showed that ATG reduced the risk of AMR in KT recipients when compared with other induction drugs; therefore, it appears to be an efficient choice of induction regimen to reduce AMR after KT.
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Soro Antilinfocitário , Rejeição de Enxerto , Imunossupressores , Transplante de Rim , Metanálise em Rede , Humanos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Soro Antilinfocitário/uso terapêutico , Basiliximab/uso terapêutico , Sobrevivência de Enxerto/efeitos dos fármacos , Alemtuzumab/uso terapêuticoRESUMO
BACKGROUND: Rituximab is an essential induction immunosuppressant for ABO-incompatible kidney transplantation (KT) (ABOi-KT). However, studies on the optimal dose of rituximab are insufficient, and there are dosage differences between transplant centers and countries. Therefore, we conducted a study to determine the survival outcomes of patients receiving the most effective and safe dose of rituximab during ABOi-KT. METHODS: Studies on rituximab dose were divided into four groups: ABO compatible, 1) placebo, 2) rituximab 200 mg, 3) rituximab 200-500 mg, and 4) rituximab 500 mg. We searched the CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases from 1970 to February 2022.9 . The inclusion criteria were adult patients (>18 years old). Reviews, observational studies, and clinical trials that did not clearly define outcomes or that did not have graft failure as an outcome were excluded. We performed direct and indirect network meta-analyses using Bayesian models and ranked different rituximab doses using a generation mixed treatment comparison (GeMTC) and Stata version 13. The NMA approach was evaluated using the GRADE framework, which specifies four levels of certainty for a given result: high, moderate, low, and very low. The outcomes included patient survival, graft failure, and bacterial and viral infections. RESULTS: Twenty-five trials, including 5,378 subjects, were divided into the following four groups: 1) placebo, 2) rituximab 200 mg, 3) rituximab 200-500 mg, and 4) rituximab 500 mg. We focused on survival outcomes according to the dose of rituximab when patients received induction therapy for ABOi-KT. The mortality rate was significantly lower in the ABO-compatible and rituximab 200 mg groups (odds ratio [OR] 0.27, 95% CrI: 0.071-0.91 and OR 0.14, 95% CrI 0.036-0.47), compared with that in the placebo group. CONCLUSIONS: We found that low-dose rituximab in ABO-i KT was effective compared to the high-dose and placebo in maintaining the survival rate. However, large-scale and long-term data are necessary for further validation of our findings. Additionally, the use of smaller doses of rituximab will require further discussion.
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Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos , Sobrevivência de Enxerto , Imunossupressores , Transplante de Rim , Metanálise em Rede , Rituximab , Humanos , Sistema ABO de Grupos Sanguíneos/imunologia , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Sobrevivência de Enxerto/efeitos dos fármacos , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/imunologiaRESUMO
BACKGROUND: Rituximab and plasmapheresis (PP) suppress and eliminate antibody production in patients experiencing antibody-mediated rejection (AMR). Herein, we discuss a case where rituximab was less effective after PP for treating AMR. CASE: A 55-year-old male patient underwent kidney transplantation. His renal function remained normal for 1 year. Subsequently, renal function declined, and (donor-specific antibodies showed positive results. A biopsy of the transplanted kidney revealed AMR. On the day of the biopsy, the medical staff administered 200 mg of rituximab, followed by IV immunoglobulin (IVIg) and PP the next day. The time interval between PP + IVIg treatment and rituximab was 12 h. As a result, the B-cell markers CD19 and CD20 did not decrease sufficiently, and the patient's creatinine and glomerular filtration rate muscles did not recover adequately. CONCLUSION: We report a case in which PP was administered shortly after rituximab injection, resulting in insufficient B-cell inhibition due to the removal of rituximab.
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Rejeição de Enxerto , Transplante de Rim , Plasmaferese , Rituximab , Humanos , Rituximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Rejeição de Enxerto/imunologia , Resultado do Tratamento , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Linfócitos B/imunologia , Linfócitos B/efeitos dos fármacosRESUMO
BACKGROUND: ABO-incompatible (ABOi) transplantation is a novel method transplantation method that carries a heightened risk of infection caused by the use of high immunosuppressant doses. This elevated risk is particularly concerning for viral infections, such as cytomegalovirus (CMV) and the BK virus (BKV) increases. Herein, we present a case where high-dose intravenous immunoglobulin (IVIG) was effective in treating viral infections after transplantation. METHODS: A 41-year-old man underwent an ABOi transplantation. The initial isoagglutinin titer was 1:32. The patient received 200 mg of rituximab, and 3 rounds of plasmapheresis were performed. Subsequently, renal function remained normal; however, 7 months later, the renal function declined, and BK nephropathy and CMV infection were diagnosed through biopsy and serologic tests. The FK level was reduced, and mycophenolate mofetil was discontinued. Although ciprofloxacin and leflunomide were administered, their effects were minimal. Therefore, high-dose IVIG (1 g/kg) was administered 5 times over 5 weeks, which led to a reduction in BK viral load and CMV infectivity in the serum. CONCLUSIONS: High-dose IVIG may serve as a promising alternative treatment to mitigate early transplant rejection and BKV and CMV infections.
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Soro Antilinfocitário , Vírus BK , Infecções por Citomegalovirus , Imunoglobulinas Intravenosas , Transplante de Rim , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Humanos , Transplante de Rim/efeitos adversos , Masculino , Adulto , Imunoglobulinas Intravenosas/uso terapêutico , Imunoglobulinas Intravenosas/administração & dosagem , Infecções por Polyomavirus/tratamento farmacológico , Infecções Tumorais por Vírus/tratamento farmacológico , Infecções Tumorais por Vírus/virologia , Infecções por Citomegalovirus/tratamento farmacológico , Soro Antilinfocitário/uso terapêutico , Soro Antilinfocitário/administração & dosagem , Sistema ABO de Grupos Sanguíneos/imunologia , Imunossupressores/uso terapêutico , Imunossupressores/administração & dosagem , Incompatibilidade de Grupos SanguíneosRESUMO
Although three-dimensional (3D) printing techniques are used to mimic macro- and micro-structures as well as multi-structural human tissues in tissue engineering, efficient target tissue regeneration requires bioactive 3D printing scaffolds. In this study, we developed a bone morphogenetic protein-2 (BMP-2)-immobilized polycaprolactone (PCL) 3D printing scaffold with leaf-stacked structure (LSS) (3D-PLSS-BMP) as a bioactive patient-tailored bone graft. The unique LSS was introduced on the strand surface of the scaffold via heating/cooling in tetraglycol without significant deterioration in physical properties. The BMP-2 adsorbed on3D-PLSS-BMPwas continuously released from LSS over a period of 32 d. The LSS can be a microtopographical cue for improved focal cell adhesion, proliferation, and osteogenic differentiation.In vitrocell culture andin vivoanimal studies demonstrated the biological (bioactive BMP-2) and physical (microrough structure) mechanisms of3D-PLSS-BMPfor accelerated bone regeneration. Thus, bioactive molecule-immobilized 3D printing scaffold with LSS represents a promising physically and biologically activated bone graft as well as an advanced tool for widespread application in clinical and research fields.
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Osteogênese , Alicerces Teciduais , Humanos , Alicerces Teciduais/química , Engenharia Tecidual/métodos , Regeneração Óssea , Poliésteres/química , Impressão TridimensionalRESUMO
Advances in nano/micro technologies in recent years have significantly improved biosensors in terms of their viability for biomedical purposes, from diagnostic to therapeutic applications, allowing for effective early detection and personalized treatment modalities [...].