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1.
Artigo em Inglês | MEDLINE | ID: mdl-39139053

RESUMO

BACKGROUND AND AIMS: Despite the development of transient elastography (TE)-based Agile scores for diagnosing fibrotic burden in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), their applicability in predicting kidney outcomes remains unclear. We aimed to investigate the association between liver fibrotic burden, as assessed by Agile scores, and the risk of incident chronic kidney disease (CKD) in patients with MASLD. METHODS: A total of 3240 participants with MASLD but without pre-existing CKD who underwent TE between July 2006 and October 2018 were selected. The primary outcome was incident CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or proteinuria (≥1+ on dipstick) on two consecutive measurements. The secondary outcome was a 25% decline in eGFR measured on two consecutive visits. RESULTS: During a median follow-up of 3.6 years, 187 participants (5.8%) developed incident CKD. When stratified into three groups according to Agile 3+ scores, multivariable Cox models revealed that risk of incident CKD was 2.77-fold (95% confidence interval [CI], 1.89-4.07; p < 0.001) higher in the high-risk group (Agile 3+ >0.68), compared to the low-risk group (Agile 3+ <0.45). During a median follow-up of 3.4 years, the high-risk group had a 2.41-fold higher risk (95% CI, 1.86-3.12; p < 0.001) of experiencing the secondary outcome, compared to the low-risk group. Similar findings were observed for Agile 4 scores. Prediction testing revealed that Agile scores were better predictors of kidney outcomes, compared to liver stiffness measured by TE. CONCLUSIONS: In patients with MASLD, but without CKD, advanced liver fibrosis measured by Agile scores was significantly associated with a higher risk of incident CKD.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39109400

RESUMO

Background: Digital health technologies have been rapidly adopted during the coronavirus disease 2019 pandemic. In Korea, a home care program, including face-to-face educational consultation and remote patient monitoring, was initiated to improve patients' quality of life. This study focused on patients with end-stage renal disease undergoing peritoneal dialysis to verify the long-term clinical effectiveness of this home care program. Methods: This retrospective cohort study was designed as a pre-post study to analyze the clinical impact of a home care program for patients undergoing peritoneal dialysis in a single tertiary care hospital. A total of 186 patients were selected from June 2017 to May 2022 to identify clinical changes after program implementation by analyzing changes in peritonitis incidence and laboratory test results. Interrupted time series analyses with ordinary least squares linear regression and chi-square tests were used. Results: At baseline, the incidence of peritonitis continuously increased by 0.480 cases per 1,000 patient-months (p = 0.02). After program initiation, the trend significantly decreased by 0.886 cases per 1,000 patient-months (p = 0.02). In addition, the proportion of individuals reaching the clinical target range had increased calcium levels (4.9%p, p = 0.003), stable hemoglobin (1.2%p, p = 0.477), phosphorus (2.8%p, p = 0.09), potassium (-1.6%p, p = 0.22), while parathyroid hormone levels decreased (-6.6%p, p = 0.005). Conclusion: With a reduction in peritonitis incidence and overall improvement in laboratory test results, our study suggests that conducting a home care program for patients undergoing peritoneal dialysis is clinically effective.

3.
Transpl Int ; 37: 12574, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39170864

RESUMO

The optimal target blood pressure for kidney transplant (KT) patients remains unclear. We included 808 KT patients from the KNOW-KT as a discovery set, and 1,294 KT patients from the KOTRY as a validation set. The main exposures were baseline systolic blood pressure (SBP) at 1 year after KT and time-varying SBP. Patients were classified into five groups: SBP <110; 110-119; 120-129; 130-139; and ≥140 mmHg. SBP trajectories were classified into decreasing, stable, and increasing groups. Primary outcome was composite kidney outcome of ≥50% decrease in eGFR or death-censored graft loss. Compared with the 110-119 mmHg group, both the lowest (adjusted hazard ratio [aHR], 2.43) and the highest SBP (aHR, 2.25) were associated with a higher risk of composite kidney outcome. In time-varying model, also the lowest (aHR, 3.02) and the highest SBP (aHR, 3.60) were associated with a higher risk. In the trajectory model, an increasing SBP trajectory was associated with a higher risk than a stable SBP trajectory (aHR, 2.26). This associations were consistent in the validation set. In conclusion, SBP ≥140 mmHg and an increasing SBP trajectory were associated with a higher risk of allograft dysfunction and failure in KT patients.


Assuntos
Pressão Sanguínea , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Transplante de Rim , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Aloenxertos , Idoso , Modelos de Riscos Proporcionais , Rejeição de Enxerto , Transplantados , Hipertensão
4.
Artigo em Inglês | MEDLINE | ID: mdl-38934045

RESUMO

Background: Patients with sensitization and blood type O experience increased waiting times for deceased-donor kidney transplantation (DDKT). While allocation benefits are needed to resolve inequity in DDKT opportunity, whether DDKT has comparable outcomes in this disadvantaged population requires further study. This study assessed these outcomes and developed a new allocation system that balances equity and utility. Methods: Patients from national and hospital cohorts from two centers in Korea were categorized as B1 to B4 (according to panel reactive antibody [PRA] positivity and ABO blood type) and A1 to A4 (based on the maximal PRA% and blood type), respectively. Competing risk and Cox regression analyses were performed to assess the effects of PRA and blood type on graft failure and mortality, respectively. Based on DDKT opportunities and posttransplant outcomes, a new scoring system for kidney allocation was developed. Results: The national and hospital cohorts included 3,311 and 819 patients, respectively, who underwent DDKT. Despite the disparities in DDKT opportunities, the graft failure rates and mortality did not differ among the different PRA and blood type groups. Furthermore, posttransplantation outcomes did not differ according to the categories with different DDKT opportunities. A new scoring system to provide additional points to disadvantaged populations was developed based on the hazard ratios for DDKT. Conclusion: A new allocation approach based on PRA and ABO blood types offers benefits to disadvantaged patients with fewer DDKT opportunities and could enhance equity without sacrificing utility in Korea, which has a long waiting time for DDKT.

5.
Micromachines (Basel) ; 15(5)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38793153

RESUMO

We introduce a micro-electromechanical system (MEMS) energy harvester, designed for capturing flow energy. Moving beyond traditional vibration-based energy harvesting, our approach incorporates a cylindrical oscillator mounted on an MEMS chip, effectively harnessing wind energy through flow-induced vibration (FIV). A highlight of our research is the development of a comprehensive fabrication process, utilizing a 5.00 µm thick cantilever beam and piezoelectric film, optimized through advanced micromachining techniques. This process ensures the harvester's alignment with theoretical predictions and enhances its operational efficiency. Our wind tunnel experiments confirmed the harvester's capability to generate a notable electrical output, with a peak voltage of 2.56 mV at an 8.00 m/s wind speed. Furthermore, we observed a strong correlation between the experimentally measured voltage frequencies and the lift force frequency observed by CFD analysis, with dominant frequencies identified in the range of 830 Hz to 867 Hz, demonstrating the potential application in actual flow environments. By demonstrating the feasibility of efficient energy conversion from ambient wind, our research contributes to the development of sustainable energy solutions and low-power wireless electron devices.

6.
Adv Sci (Weinh) ; 11(21): e2307353, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38502886

RESUMO

The tissue-specific heart decellularized extracellular matrix (hdECM) demonstrates a variety of therapeutic advantages, including fibrosis reduction and angiogenesis. Consequently, recent research for myocardial infarction (MI) therapy has utilized hdECM with various delivery techniques, such as injection or patch implantation. In this study, a novel approach for hdECM delivery using a wet adhesive paintable hydrogel is proposed. The hdECM-containing paintable hydrogel (pdHA_t) is simply applied, with no theoretical limit to the size or shape, making it highly beneficial for scale-up. Additionally, pdHA_t exhibits robust adhesion to the epicardium, with a minimal swelling ratio and sufficient adhesion strength for MI treatment when applied to the rat MI model. Moreover, the adhesiveness of pdHA_t can be easily washed off to prevent undesired adhesion with nearby organs, such as the rib cages and lungs, which can result in stenosis. During the 28 days of in vivo analysis, the pdHA_t not only facilitates functional regeneration by reducing ventricular wall thinning but also promotes neo-vascularization in the MI region. In conclusion, the pdHA_t presents a promising strategy for MI treatment and cardiac tissue regeneration, offering the potential for improved patient outcomes and enhanced cardiac function post-MI.


Assuntos
Matriz Extracelular Descelularizada , Modelos Animais de Doenças , Hidrogéis , Infarto do Miocárdio , Ratos Sprague-Dawley , Animais , Ratos , Hidrogéis/química , Matriz Extracelular Descelularizada/química , Masculino , Matriz Extracelular/química , Miocárdio
7.
Clin Transl Med ; 14(3): e1631, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38504554

RESUMO

BACKGROUND: Cold ischemia-reperfusion injury (IRI) is an unavoidable complication of kidney transplantation. We investigated the role of regulatory T cells (Treg) in cold IRI and whether the interleukin (IL)-2/anti-IL-2 antibody complex (IL-2C) can ameliorate cold IRI. METHODS: We developed a cold IRI mouse model using kidney transplantation and analyzed the IL-2C impact on cold IRI in acute, subacute and chronic phases. RESULTS: Treg transfer attenuated cold IRI, while Treg depletion aggravated cold IRI. Next, IL-2C administration prior to IRI mitigated acute renal function decline, renal tissue damage and apoptosis and inhibited infiltration of effector cells into kidneys and pro-inflammatory cytokine expression on day 1 after IRI. On day 7 after IRI, IL-2C promoted renal regeneration and reduced subacute renal damage. Furthermore, on day 28 following IRI, IL-2C inhibited chronic fibrosis. IL-2C decreased reactive oxygen species-mediated injury and improved antioxidant function. When IL-2C was administered following IRI, it also increased renal regeneration with Treg infiltration and suppressed renal fibrosis. In contrast, Treg depletion in the presence of IL-2C eliminated the positive effects of IL-2C on IRI. CONCLUSION: Tregs protect kidneys from cold IRI and IL-2C inhibited cold IRI by increasing the renal Tregs, suggesting a potential of IL-2C in treating cold IRI. KEY POINTS: Interleukin (IL)-2/anti-IL-2 antibody complex attenuated acute renal injury, facilitated subacute renal regeneration and suppressed chronic renal fibrosis after cold ischemia-reperfusion injury (IRI) by increasing the renal Tregs. IL-2/anti-IL-2 antibody complex decreased reactive oxygen species-mediated injury and improved antioxidant function. This study suggests the therapeutic potential of the IL-2/anti-IL-2 antibody complex in kidney transplantation-associated cold IR.


Assuntos
Injúria Renal Aguda , Transplante de Rim , Traumatismo por Reperfusão , Animais , Camundongos , Interleucina-2/metabolismo , Linfócitos T Reguladores , Complexo Antígeno-Anticorpo , Transplante de Rim/efeitos adversos , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Rim , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Fibrose
8.
Biomater Sci ; 12(7): 1847-1863, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38411258

RESUMO

Axon regeneration and Schwann cell proliferation are critical processes in the repair and functional recovery of damaged neural tissues. Biomaterials can play a crucial role in facilitating cell proliferative processes that can significantly impact the target tissue repair. Chemical decellularization and supercritical fluid-based decellularization methods are similar approaches that eliminate DNA from native tissues for tissue-mimetic biomaterial production by using different solvents and procedures to achieve the final products. In this study, we conducted a comparative analysis of these two methods in the context of nerve regeneration and neuron cell differentiation efficiency. We evaluated the efficacy of each method in terms of biomaterial quality, preservation of extracellular matrix components, promotion of neuronal cell differentiation and nerve tissue repair ability in vivo. Our results indicate that while both methods produce high-quality biomaterials, supercritical fluid-based methods have several advantages over conventional chemical decellularization, including better preservation of extracellular matrix components and mechanical properties and superior promotion of cellular responses. We conclude that supercritical fluid-based methods show great promise for biomaterial production for nerve regeneration and neuron cell differentiation applications.


Assuntos
Regeneração Nervosa , Tecido Nervoso , Matriz Extracelular/química , Axônios , Materiais Biocompatíveis/química , Engenharia Tecidual/métodos , Alicerces Teciduais/química
9.
Sci Rep ; 14(1): 2635, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302674

RESUMO

The waiting time to deceased-donor kidney transplantation (DDKT) is long in Asian countries. We investigated the impact of sensitization and ABO blood type (ABO) on DDKT opportunity using two Korean cohorts: a hospital cohort from two centers and a national database. The impact of panel reactive antibody (PRA) based on the maximal PRA% and ABO on DDKT accessibility was analyzed using a competing risks regression model. In the hospital cohort (n = 4722), 88.2%, 8.7%, and 3.1% of patients belonged to < 80%, 80-99%, and ≥ 99% PRA groups, respectively, and 61.1%, 11.6%, and 27.3% belonged to A or B, AB, and O blood types, respectively. When PRA and ABO were combined, PRA < 80%/A or B and 80 ≤ PRA < 99%/AB had fewer DDKT opportunities (median, 12 years; subdistribution hazard ratio [sHR], 0.71) compared with PRA < 80%/AB (median, 11 years). Also, PRA < 80%/O, 80 ≤ PRA < 99%/A or B, and PRA ≥ 99%/AB had a much lower DDKT opportunity (median, 13 years; sHR, 0.49). Furthermore, 80 ≤ PRA < 99%/O and PRA ≥ 99%/non-AB had the lowest DDKT opportunity (sHR, 0.28). We found similar results in the national cohort (n = 18,974). In conclusion, an integrated priority system for PRA and ABO is needed to reduce the inequity in DDKT opportunities, particularly in areas with prolonged waiting times.


Assuntos
Transplante de Rim , Humanos , Transplante de Rim/métodos , Doadores de Tecidos , Listas de Espera , Rim , Tipagem e Reações Cruzadas Sanguíneas
10.
J Control Release ; 368: 140-156, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38373473

RESUMO

Traumatic brain injuries(TBI) pose significant challenges to human health, specifically neurological disorders and related motor activities. After TBI, the injured neuronal tissue is known for hardly regenerated and recovered to their normal neuron physiology and tissue compositions. For this reason, tissue engineering strategies that promote neuronal regeneration have gained increasing attention. This study explored the development of a novel neural tissue regeneration cryogel by combining brain-derived decellularized extracellular matrix (ECM) with heparin sulfate crosslinking that can perform nerve growth factor (NGF) release ability. Morphological and mechanical characterizations of the cryogels were performed to assess their suitability as a neural regeneration platform. After that, the heparin concnentration dependent effects of varying NGF concentrations on cryogel were investigated for their controlled release and impact on neuronal cell differentiation. The results revealed a direct correlation between the concentration of released NGF and the heparin sulfate ratio in cryogel, indicating that the cryogel can be tailored to carry higher loads of NGF with heparin concentration in cryogel that induced higher neuronal cell differentiation ratio. Furthermore, the study evaluated the NGF loaded cryogels on neuronal cell proliferation and brain tissue regeneration in vivo. The in vivo results suggested that the NGF loaded brain ECM derived cryogel significantly affects the regeneration of brain tissue. Overall, this research contributes to the development of advanced neural tissue engineering strategies and provides valuable insights into the design of regenerative cryogels that can be customized for specific therapeutic applications.


Assuntos
Lesões Encefálicas Traumáticas , Engenharia Tecidual , Humanos , Encéfalo , Lesões Encefálicas Traumáticas/terapia , Criogéis , Matriz Extracelular , Heparina , Fator de Crescimento Neural/farmacologia , Regeneração Nervosa , Sulfatos , Engenharia Tecidual/métodos
11.
Sci Rep ; 14(1): 1966, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263396

RESUMO

Death with a functioning graft is important cause of graft loss after kidney transplantation. However, little is known about factors predicting death with a functioning graft among kidney transplant recipients. In this study, we evaluated the association between post-transplant creatinine-cystatin C ratio and death with a functioning graft in 1592 kidney transplant recipients. We divided the patients into tertiles based on sex-specific creatinine-cystatin C ratio. Among the 1592 recipients, 39.5% were female, and 86.1% underwent living-donor kidney transplantation. The cut-off value for the lowest creatinine-cystatin C ratio tertile was 0.86 in males and 0.73 in females. The lowest tertile had a significantly lower 5-year patient survival rate and was independently associated with death with a functioning graft (adjusted hazard ratio 2.574, 95% confidence interval 1.339-4.950, P < 0.001). Infection was the most common cause of death in the lowest tertile group, accounting for 62% of deaths. A low creatinine-cystatin C ratio was significantly associated with an increased risk of death with a functioning graft after kidney transplantation.


Assuntos
Cistatina C , Transplante de Rim , Masculino , Humanos , Feminino , Creatinina , Transplantados , Razão de Masculinidade
12.
J Infect Dis ; 229(1): 108-116, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-37470458

RESUMO

BACKGROUND: We investigated whether higher fibrotic burden was independently associated with poorer kidney outcomes in patients with hepatitis B virus (HBV)-related cirrhosis. METHODS: A total of 1691 patients with radiologically diagnosed HBV-related cirrhosis but without baseline chronic kidney disease (CKD) who underwent transient elastography (TE) between March 2012 and August 2018 were selected. The study outcome was the composite of development of incident CKD, defined as the occurrence of estimated glomerular filtration rate (eGFR) <60 mL/minute/1.73 m2 or proteinuria (≥1+ on dipstick test) on 2 consecutive measurements during follow-up, 50% decline in eGFR or onset of end-stage kidney disease (initiation of chronic dialysis), or all-cause mortality. RESULTS: The mean age was 53.4 years and 1030 (60.9%) patients were male. During 8379 person-years of follow-up (median 5.2 years), 60 (3.5%) patients experienced study outcomes. When stratified according to TE-defined fibrotic burden, multivariable Cox models revealed that risk of poorer kidney outcomes was 2.77-fold (95% confidence interval, 1.16-6.63; P < .001) higher in patients with liver stiffness range indicating cirrhosis (≥11.7 kPa), compared to those without significant liver fibrosis (<7.9 kPa). These associations remained significant even after adjusting for vigorous confounders. CONCLUSIONS: Higher fibrotic burden assessed using TE was independently associated with poorer kidney outcomes in patients with HBV-related cirrhosis.


Assuntos
Técnicas de Imagem por Elasticidade , Hepatite B Crônica , Insuficiência Renal Crônica , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Vírus da Hepatite B , Cirrose Hepática/etiologia , Rim , Insuficiência Renal Crônica/complicações , Técnicas de Imagem por Elasticidade/efeitos adversos , Hepatite B Crônica/complicações
13.
Am J Nephrol ; 55(2): 235-244, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38035562

RESUMO

INTRODUCTION: ABO-incompatible (ABOi) living donor kidney transplantation (LDKT) is considered only for patients who do not have an ABO-compatible (ABOc) LD. Therefore, a clinically practical question is whether to proceed with ABOi LDKT or remain on dialysis while waiting for ABOc deceased donor kidney transplantation (DDKT). However, this issue has not been addressed in Asian countries, where ABOi LDKT programs are more active than DDKT programs. METHODS: A total of 426 patients underwent ABOi-LDKT between 2010 and 2020 at Seoul National University Hospital and Severance Hospital, Korea. We compared outcomes between the ABOi-LDKT and the propensity-matched control groups (waiting-list-only group, n = 1,278; waiting-list-or-ABOc-DDKT group, n = 1,278). RESULTS: The ABOi-LDKT group showed a significantly better patient survival rate than the waiting-list-only group (p = 0.001) and the waiting-list-or-ABOc-DDKT group (p = 0.048). When the ABOi-LDKT group was categorized into a high-titer group (peak anti-ABO titer ≥1:128) and a low-titer group (peak anti-ABO titer ≤1:64), the low-titer group showed better patient survival rates than those of the waiting-list-or-ABOc-DDKT group (p = 0.046) or the waiting-list-only group (p = 0.004). In contrast, the high-titer ABOi-LDKT group showed no significant benefit in patient survival compared to the waiting-list-or-ABOc-DDKT group. Death-censored graft survival in the ABOi-LDKT group was not significantly different from that in the ABOc-DDKT group (p = 0.563). CONCLUSION: The ABOi-LDKT group has better outcomes than the waiting-list-or-ABOc-DDKT group in a country with a long waiting time.


Assuntos
Transplante de Rim , Humanos , Doadores Vivos , Incompatibilidade de Grupos Sanguíneos , Rejeição de Enxerto/epidemiologia , Rim , Sistema ABO de Grupos Sanguíneos , Sobrevivência de Enxerto
14.
Clin Transplant ; 38(1): e15178, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37922208

RESUMO

BACKGROUND: The Living Kidney Donor Profile Index (LKDPI) was developed in the United States to predict graft outcomes based on donor characteristics. However, there are significant differences in donor demographics, access to transplantation, proportion of ABO incompatibility, and posttransplant mortality in Asian countries compared with the United States. METHODS: We evaluated the clinical relevance of the LKDPI score in a Korean kidney transplant cohort by analyzing 1860 patients who underwent kidney transplantation between 2000 and 2019. Patients were divided into three groups according to LKDPI score: <0, 1-19.9, and ≥20. RESULTS: During a median follow-up of 119 months, 232 recipients (12.5%) experienced death-censored graft loss, and 98 recipients (5.3%) died. High LKDPI scores were significantly associated with increased risk of death-censored graft loss independent of recipient characteristics (LKDPI 1-19.9: HR 1.389, 95% CI 1.036-1.863; LKDPI ≥20: HR 2.121, 95% CI 1.50-2.998). High LKDPI score was also significantly associated with increased risk of biopsy-proven acute rejection and impaired graft renal function. By contrast, overall patient survival rates were comparable among the LKDPI groups. CONCLUSION: High LKDPI scores were associated with an increased risk of death-censored graft loss, biopsy-proven acute rejection, and impaired graft renal function among a Korean kidney transplant cohort.


Assuntos
Transplante de Rim , Humanos , Estados Unidos , Relevância Clínica , Doadores Vivos , Incompatibilidade de Grupos Sanguíneos , Transplantados , Sobrevivência de Enxerto , República da Coreia/epidemiologia , Rejeição de Enxerto/etiologia
15.
Membranes (Basel) ; 13(9)2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37755216

RESUMO

In this study, blended perfluorinated sulfonic acid (PFSA) ionomers with equivalent weights (EWs, g/mol) of ~1000, 980, and 830 are prepared. Catalyst layers (CLs), using blended PFSA ionomers, with different side chain lengths and EWs are investigated and compared to CLs using single ionomers. The ion exchange capacity results confirm that blended ionomers have the target EWs. As a result, blended ionomers exhibit higher ion conductivity than single ionomers at all temperatures due to the higher water uptake of the blended ionomers. This implies that blended ionomers have a bulk structure to form a competent free volume compared to single ionomers. Blended ionomers with short side chains and low EWs can help reduce the activation energy in proton conduction due to enhanced hydrophobic and hydrophilic segregation. In addition, when using the blended ionomer, the CLs form a more porous microstructure to help reduce the resistance of oxygen transport and contributes to lower mass transfer loss. This effect is proven in fuel cell operations at not a lower temperature (70 °C) and full humidification (100%) but at an elevated temperature (80 °C) and lower relative humidity (50 and 75%). Blended ionomer-based CLs with a higher water uptake and porous CL structure result in improved fuel cell performance with better mass transport than single ionomer-based CLs.

16.
Nat Commun ; 14(1): 5382, 2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37666819

RESUMO

Regulatory T cells (Treg) are CD4+ T cells with immune-suppressive function, which is defined by Foxp3 expression. However, the molecular determinants defining the suppressive population of T cells have yet to be discovered. Here we report that the cell surface protein Lrig1 is enriched in suppressive T cells and controls their suppressive behaviors. Within CD4+ T cells, Treg cells express the highest levels of Lrig1, and the expression level is further increasing with activation. The Lrig1+ subpopulation from T helper (Th) 17 cells showed higher suppressive activity than the Lrig1- subpopulation. Lrig1-deficiency impairs the suppressive function of Treg cells, while Lrig1-deficient naïve T cells normally differentiate into other T cell subsets. Adoptive transfer of CD4+Lrig1+ T cells alleviates autoimmune symptoms in colitis and lupus nephritis mouse models. A monoclonal anti-Lrig1 antibody significantly improves the symptoms of experimental autoimmune encephalomyelitis. In conclusion, Lrig1 is an important regulator of suppressive T cell function and an exploitable target for treating autoimmune conditions.


Assuntos
Autoimunidade , Colite , Animais , Camundongos , Linfócitos T CD4-Positivos , Linfócitos T Reguladores , Transferência Adotiva , Fatores de Transcrição , Fatores de Transcrição Forkhead/genética
17.
Antioxidants (Basel) ; 12(6)2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37371990

RESUMO

Cordycepin, also known as 3'-deoxyadenosine, is a major active ingredient of Cordyceps militaris with diverse pharmacological effects. Due to its limited supply, many attempts have been conducted to enhance the cordycepin content. As part of this study, eight medicinal plants were supplemented with cultivation substrates of Cordyceps to increase the cordycepin content. Cordyceps cultivated on brown rice supplemented with Mori Folium, Curcumae Rhizoma, Saururi Herba, and Angelicae Gigantis Radix exhibited increased cordycepin content compared to a brown rice control. Among them, the addition of 25% Mori Folium increased the cordycepin content up to 4 times. Adenosine deaminase (ADA) modulates the deamination of adenosine and deoxyadenosine, and the inhibitors have therapeutic potential with anti-proliferative and anti-inflammatory properties. As ADA is also known to be involved in converting cordycepin to 3'-deoxyinosine, the inhibitory activity of medicinal plants on ADA was measured by spectrophotometric analysis using cordycepin as a substrate. As expected, Mori Folium, Curcumae Rhizoma, Saururi Herba, and Angelicae Gigas Radix strongly inhibited ADA activity. Molecular docking analysis also showed the correlation between ADA and the major components of these medicinal plants. Conclusively, our research suggests a new strategy of using medicinal plants to enhance cordycepin production in C. militaris.

18.
Sci Rep ; 13(1): 7682, 2023 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-37169835

RESUMO

De novo donor-specific antibody (dnDSA) is associated with a higher risk of kidney graft failure. However, it is unknown whether preemptive treatment of subclinical dnDSA is beneficial. Here, we assessed the efficacy of high-dose intravenous immunoglobulin (IVIG) and rituximab combination therapy for subclinical dnDSA. An open-label randomized controlled clinical trial was conducted at two Korean institutions. Adult (aged ≥ 19 years) kidney transplant patients with subclinical class II dnDSA (mean fluorescence intensity ≥ 1000) were enrolled. Eligible participants were randomly assigned to receive rituximab or rituximab with IVIG at a 1:1 ratio. The primary endpoint was the change in dnDSA titer at 3 and 12 months after treatment. A total of 46 patients (24 for rituximab and 22 for rituximab with IVIG) were included in the analysis. The mean baseline estimated glomerular filtration rate was 66.7 ± 16.3 mL/min/1.73 m2. The titer decline of immune-dominant dnDSA at 12 months in both the preemptive groups was significant. However, there was no difference between the two groups at 12 months. Either kidney allograft function or proteinuria did not differ between the two groups. No antibody-mediated rejection occurred in either group. Preemptive treatment with high-dose IVIG combined with rituximab did not show a better dnDSA reduction compared with rituximab alone.Trial registration: IVIG/Rituximab versus Rituximab in Kidney Transplant With de Novo Donor-specific Antibodies (ClinicalTrials.gov Identifier: NCT04033276, first trial registration (26/07/2019).


Assuntos
Transplante de Rim , Adulto , Humanos , Transplante de Rim/efeitos adversos , Imunoglobulinas Intravenosas/uso terapêutico , Rituximab/uso terapêutico , Isoanticorpos , Rejeição de Enxerto , Sobrevivência de Enxerto , Estudos Retrospectivos , Antígenos HLA
19.
Medicine (Baltimore) ; 102(19): e33695, 2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37171361

RESUMO

BACKGROUND: Patients with kidney failure must make complicated decisions about the dialysis modalities used either at home or in-hospital. Different options have varying levels of impact on patients' physical and psychological conditions and their social life. The purpose of this study was to evaluate the implementation of an intervention designed to achieve shared decision making (SDM) in patients' options for dialysis. METHODS: SDM was performed after consent was written for stage 5 chronic kidney disease patients before dialysis, and 435 cases were performed in 408 patients from December 16, 2019 to June 30, 2021. Among these, 101 patients were compared by SDM measurement scale, patient satisfaction, disease recognition scale survey, and dialysis method. RESULTS: The average age of participants was 56 years, with a gender composition of 55 males (54.5%) and 46 females (45.5%). Following SDM, the final dialysis methods decided upon by patients and clinicians were peritoneal dialysis (67 patients, 66.3%), hemodialysis (22 patients, 21.8%), and kidney transplantation (1 patient, 1.0%). CONCLUSIONS: Among participating patients, SDM was effective when used to decide on dialysis treatment, and patients were satisfied with the dialysis method decision process. On the disease awareness scale, those who participated in this project had relatively high positive and low negative perceptions, so it can be concluded that SDM was relatively effective. The implementation of SDM was helpful in selecting patients' best dialysis methods, and SDM scale results were higher in the peritoneal dialysis group than in the hemodialysis group.


Assuntos
Falência Renal Crônica , Diálise Peritoneal , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Diálise Renal/métodos , Tomada de Decisão Compartilhada , Falência Renal Crônica/terapia , Falência Renal Crônica/psicologia , Inquéritos e Questionários , Tomada de Decisões , Participação do Paciente/métodos
20.
J Nephrol ; 36(9): 2571-2580, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37106218

RESUMO

INTRODUCTION: Early antibody-mediated rejection has been reported to increase chronic antibody-mediated rejection and decrease graft survival in kidney transplantation. However, the impact of early antibody-mediated rejection in ABO-incompatible kidney transplantation remains unclear. METHODS: We retrospectively analyzed living-donor kidney transplantation patients from two Korean centers. Patients were categorized based on ABO compatibility and early antibody-mediated rejection within 1 year. The primary outcome was chronic antibody-mediated rejection. The secondary outcomes were production of de novo donor-specific antibody and composite kidney outcome, defined as graft loss or a decline in estimated glomerular filtration rate to below 30 mL/min/1.73 m2. RESULTS: A total of 1639 patients were analyzed, including 1292 patients who underwent ABO-compatible kidney transplantation and 347 patients who underwent ABO-incompatible kidney transplantation. ABO-incompatible kidney transplantation had a lower risk of de novo donor-specific antibody production (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.48-0.95) and chronic antibody-mediated rejection (HR 0.33, 95% CI 0.12-0.92) with a comparable risk of the composite kidney outcome (HR 1.06, 95% CI 0.71-1.59) compared to ABO-compatible kidney transplantation. When outcomes of ABO-incompatible kidney transplantation were analyzed according to early antibody-mediated rejection, ABO-incompatible kidney transplantation without antibody-mediated rejection had a lower risk of de novo donor-specific antibody production (HR 0.60, 95% CI 0.41-0.88) and chronic antibody-mediated rejection (HR 0.28, 95% CI 0.09-0.91) than ABO-compatible kidney transplantation without antibody-mediated rejection. However, ABO-incompatible kidney transplantation with antibody-mediated rejection showed a higher risk of de novo donor-specific antibody production and similar risk of chronic antibody-mediated rejection compared to ABO-compatible kidney transplantation without antibody-mediated rejection. CONCLUSIONS: ABO-incompatible kidney transplantation showed a lower risk of de novo donor-specific antibody production and chronic antibody-mediated rejection compared to ABO-compatible kidney transplantation; however, early antibody-mediated rejection abrogated these beneficial effects of ABO-incompatible kidney transplantation.


Assuntos
Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Imunossupressores , Estudos Retrospectivos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/prevenção & controle , Incompatibilidade de Grupos Sanguíneos , Doadores Vivos , Sobrevivência de Enxerto , Sistema ABO de Grupos Sanguíneos
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