Paintable Decellularized-ECM Hydrogel for Preventing Cardiac Tissue Damage.

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.

Interleukin-2/anti-interleukin-2 immune complex attenuates cold ischemia-reperfusion injury after kidney transplantation by increasing renal regulatory T cells.

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.

Decellularized brain extracellular matrix based NGF-releasing cryogel for brain tissue engineering in traumatic brain injury.

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.

Impact of sensitization and ABO blood types on the opportunity of deceased-donor kidney transplantation with prolonged waiting time.

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.

Comparative analysis of supercritical fluid-based and chemical-based decellularization techniques for nerve tissue regeneration.

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.

Creatinine-cystatin C ratio and death with a functioning graft in kidney transplant recipients.

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.

Fibrotic Burden in Patients With Hepatitis B Virus-Related Cirrhosis Is Independently Associated With Poorer Kidney Outcomes.

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.

Outcomes of ABO-Incompatible Living Donor Kidney Transplantation Compared to Waiting or Deceased Donor Kidney Transplantation.

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.

Clinical relevance of the living kidney donor profile index in Korean kidney transplant recipients.

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.

Effect of Blended Perfluorinated Sulfonic Acid Ionomer Binder on the Performance of Catalyst Layers in Polymer Electrolyte Membrane Fuel Cells.

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.

Lrig1-expression confers suppressive function to CD4+ cells and is essential for averting autoimmunity via the Smad2/3/Foxp3 axis.

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.

Adenosine Deaminase Inhibitory Activity of Medicinal Plants: Boost the Production of Cordycepin in Cordyceps militaris.

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.

Comparison of high-dose IVIG and rituximab versus rituximab as a preemptive therapy for de novo donor-specific antibodies in kidney transplant patients.

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).

Shared decision-making intervention regarding dialysis modality in patients with CKD stage 5.

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.

Comparison of decline in renal function between patients with chronic hepatitis B with or without antiviral therapy.

BACKGROUND AND AIMS: Renal function can deteriorate in patients with chronic hepatitis B (CHB). We compared the risk of renal function decline between patients with untreated and treated CHB receiving antiviral therapy. METHODS: This retrospective study included 1061 untreated CHB patients, and 366 on tenofovir alafenamide (TAF), 190 on besifovir dipivoxil maleate (BSV), and 2029 on entecavir (ETV). The primary outcome was renal function decline, a ≥ one-stage increase in chronic kidney disease for ≥3 consecutive months. RESULTS: The incidence and risk of renal function decline were significantly higher in the 1:1 propensity score-matched treated group (588 pairs) than in the untreated (2.7 per 1000 person-years [PYs] vs. 1.3 per 1000 PYs, adjusted hazard ratio [aHR] = 2.29, all p < 0.001). The matched TAF group (222 pairs) showed a similar risk for the primary outcome (aHR = 1.89, p = 0.107) despite a significantly higher incidence thereof, compared to the untreated (3.9 vs. 1.9 per 1000 PYs, p = 0.042). The matched BSV and untreated groups (107 pairs) showed no significant differences in the incidence and risk. However, ETV users (541 pairs) carried a significantly higher outcome incidence and risk than the matched untreated (3.6 vs. 1.1 per 1000 PYs, aHR = 1.05, all p < 0.001). Compared to each matched untreated group, changes in the estimated glomerular filtration rate over time were greater in the ETV group (p = 0.010), despite being similar in the TAF (p = 0.073) and BSV groups (p = 0.926). CONCLUSIONS: Compared with untreated patients, TAF or BSV users showed similar risk, whereas ETV users showed a higher risk of renal function decline.

Impact of ABO incompatibility and early antibody-mediated rejection on chronic antibody-mediated rejection in kidney transplant patients.

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.

Impact of iron status on kidney outcomes in kidney transplant recipients.

Iron plays an important role in hemodynamics and the immunity, independent of anemia. Since dynamic changes occur in iron storage after kidney transplantation (KT), we investigated the association between iron status and kidney outcomes in KT patients. We analyzed data from the KoreaN cohort study for Outcome in patients With KT (KNOW-KT). The iron status was classified into three groups based on ferritin or transferrin saturation (TSAT) levels one year after KT, with reference ranges of 20‒35% and 100‒300 ng/mL for TSAT and ferritin, respectively. The primary outcome was the composite outcome, which consisted of death, graft failure, and an estimated glomerular filtration rate decline ≥ 50%. In total, 895 patients were included in the final analysis. During a median follow-up of 5.8 years, the primary outcome occurred in 94 patients (19.8/1000 person-years). TSAT levels decreased one year after KT and thereafter gradually increased, whereas ferritin levels were maintained at decreased levels. The adjusted hazard ratios (95% confidence intervals) for the composite outcome were 1.67 (1.00-2.77) and 1.20 (0.60-2.40) in the TSAT > 35% and ferritin > 300 ng/mL groups, respectively. High iron status with high TSAT levels increases the risk of graft failure or kidney functional deterioration after KT.

Low skeletal muscle mass is associated with mortality in kidney transplant recipients.

Muscle wasting in chronic kidney disease is associated with increased cardiovascular events, morbidity, and mortality. However, whether pretransplantation skeletal muscle mass affects kidney transplantation (KT) outcomes has not been established. We analyzed 623 patients who underwent KT between 2004 and 2019. We measured the cross-sectional area of total skeletal muscle at the third lumbar vertebra level on pretransplantation computed tomography scan. The patients were grouped into low and normal skeletal muscle mass groups based on the sex-specific skeletal muscle mass index lowest quartile. During the entire follow-up period, 45 patients (7.2%) died and 56 patients (9.0%) experienced death-censored graft loss. Pretransplantation low skeletal muscle mass was independently associated with all-cause mortality (adjusted hazard ratio, 2.269; 95% confidence interval, 1.232-4.182). Low muscle mass was also associated with an increased risk of hospital readmission within 1 year after transplantation. Death-censored graft survival rates were comparable between the 2 groups. The low muscle group showed higher creatinine-based estimated glomerular filtration rates (eGFRs) than the normal muscle group. Although cystatin C-based eGFRs were measured in only one-third of patients, cystatin C-based eGFRs were comparable between the 2 groups. Pretransplantation low skeletal muscle mass index is associated with an increased risk of mortality and hospital readmission after KT.

The oxidative phosphorylation inhibitor IM156 suppresses B-cell activation by regulating mitochondrial membrane potential and contributes to the mitigation of systemic lupus erythematosus.

Current treatment strategies for autoimmune diseases may not sufficiently control aberrant metabolism in B-cells. To address this concern, we investigated a biguanide derivative, IM156, as a potential regulator for B-cell metabolism in vitro and in vivo on overactive B-cells stimulated by the pro-inflammatory receptor TLR-9 agonist CpG oligodeoxynucleotide, a mimic of viral/bacterial DNA. Using RNA sequencing, we analyzed the B-cell transcriptome expression, identifying the major molecular pathways affected by IM156 in vivo. We also evaluated the anti-inflammatory effects of IM156 in lupus-prone NZB/W F1 mice. CD19+B-cells exhibited higher mitochondrial mass and mitochondrial membrane potential compared to T-cells and were more susceptible to IM156-mediated oxidative phosphorylation inhibition. In vivo, IM156 inhibited mitochondrial oxidative phosphorylation, cell cycle progression, plasmablast differentiation, and activation marker levels in CpG oligodeoxynucleotide-stimulated mouse spleen B-cells. Interestingly, IM156 treatment significantly increased overall survival, reduced glomerulonephritis and inhibited B-cell activation in the NZB/W F1 mice. Thus, our data indicated that IM156 suppressed the mitochondrial membrane potentials of activated B-cells in mice, contributing to the mitigation of lupus activity. Hence, IM156 may represent a therapeutic alternative for autoimmune disease mediated by B-cell hyperactivity.

A resveratrol oligomer, hopeaphenol suppresses virulence activity of Pectobacterium atrosepticum via the modulation of the master regulator, FlhDC.

Pectobacterium atrosepticum (P. atrosepticum: Pba) which causes potato soft rot and blackleg is a notorious plant pathogen worldwide. Discovery of new types of antimicrobial chemicals that target specifically to virulence factors such as bacterial motility and extracellular enzymes is required for protecting crops from pathogenic infection. A transcriptomic analysis of Pba upon hopeaphenol treatment revealed that bacterial motility-related gene expression, including a master regulator flhDC genes, was significantly influenced by hopeaphenol. We further generated a double knock-out mutant of flhDC genes by CRISPR/Cas9 system and confirmed phenotypic changes in bacterial motility, transcription of extracellular enzymes, and disease development consistent with the result of wild-type treated with hopeaphenol. The hopeaphenol-treated Pba strains, wild-type, double mutant, and complemented strain were unable to secrete the enzymes in vitro, while ΔflhDC double mutant strain reduced the secretion. Thus, our study supports that FlhDC is essential for the virulence of Pba, and proposes that hopeaphenol modulates FlhDC-dependent virulence pathways, suggesting a potential of hopeaphenol as an anti-virulence agent to manage potato soft rot and blackleg diseases.