Scarcity Of Donors Research Articles

Heparin Immobilization Enhances Hemocompatibility, Re-Endothelization, and Angiogenesis of Decellularized Liver Scaffolds

Bioengineered livers are currently an acceptable alternative to orthotopic liver transplants to overcome the scarcity of donors. However, the challenge of using a bioengineered liver is the lack of an intact endothelial layer in the vascular network leading to thrombosis. Heparin-modified surfaces have been demonstrated to decrease thrombogenicity in earlier research. However, in our study, we aimed to apply heparin immobilization to enhance the hemocompatibility, endothelial cell (EC) adhesion, and angiogenesis of rat decellularized liver scaffolds (DLS). Heparin was immobilized on the DLS by the end-point attachment technique. The scaffold’s hemocompatibility was assessed using ex vivo blood perfusion and platelet adhesion studies. The heparinized scaffold (HEP-DLS) showed a significantly reduced thrombogenicity and platelet aggregation. HEP-DLS was recellularized with EA.hy926 cells via the portal vein and maintained in the bioreactor for 7 days, showing increased EC adhesion and coverage within the blood vessels. The Resazurin reduction assay confirmed the presence of actively proliferating cells in the HEP-DLS. The scaffolds were implanted subcutaneously into the dorsum of mice for 21 days to evaluate cell migration and angiogenesis. The results showed significant increases in the number of blood vessels in the HEP-DLS group. Our results demonstrated that heparin immobilization reduces thrombosis, promotes re-endothelialization, and enhances angiogenesis in DLS. The research provides insight into the potential use of heparin in the formation of a functioning vasculature.

Abstract 4113494: Gut Microbiota Modulation by Immunosuppression and Cardiac Cell Therapy in a Nonhuman Primate Ischemia/Reperfusion Model of Cardiac Regeneration

End-stage ischemic heart disease necessitates heart transplantation, and emerging cell therapy presents a promising solution to address donor scarcity. Disruption of gut microbiota significantly influences various diseases and treatments, including transplantation. However, the impact of immunosuppression and cardiac cell therapy on gut microbiota remains largely unexplored. To elucidate this relationship, we investigated gut microbiota dynamics in response to immunosuppression and cell therapy in a nonhuman primate (NHP) cardiac ischemia/reperfusion (IR) model, with controlled genetic, dietary, and environmental factors. Immunosuppression enriched anaerobes (Faecalibacterium, Streptococcus, Anaerovibrio, Dialister), increasing gut microbiota diversity. These changes correlated with metabolic shifts towards amino acid metabolism and nucleosides/nucleotides biosynthesis. Combined treatment of human induced pluripotent stem cell (iPSC)-derived endothelial cells (EC) and cardiomyocytes (CM) also increased gut microbiota diversity, with specific genera alterations. The EC/CM co-treatment group displayed gut microbiota resembling the pre-injury group, with host metabolism shifting towards amino acid and fatty acid/lipid biosynthesis post-cell therapy. These observed microbiota changes and metabolic shifts could serve as biomarkers for monitoring cell therapy and immunosuppression outcomes, offering potential therapeutic targets to enhance efficacy.

Challenges in Beta Cell Replacement for Type 1 Diabetes.

Type 1 diabetes (T1D) presents a significant global health challenge, characterized by immune-mediated destruction of pancreatic beta-cells. Achieving therapeutic goals such as prevention of immune destruction, preservation of beta-cell mass, and automated insulin delivery remains complex due to the disease's heterogeneity. This review explores the advancements and challenges in beta-cell replacement therapies, including pancreas and islet cell transplantation, stem cell-derived β-cell generation, and biotechnological innovations. Pancreas transplantation, especially simultaneous pancreas and kidney transplantation (SPK), has evolved significantly, offering insulin independence and improved quality of life despite surgical and immunological complications. Allogeneic islet transplantation, though less invasive, faces challenges such as donor scarcity, immunosuppressive therapy, and variable long-term success. Innovations in stem cell therapy, particularly using human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), promise an unlimited source of β-cells. However, translating these advances into clinical applications involves overcoming technical, biological, and ethical hurdles. Strategies such as immunomodulation, encapsulation, and genetic engineering are critical to enhancing the viability and integration of transplanted cells. This review provides a comprehensive overview of the scientific intricacies and potential of β-cell replacement therapies, emphasizing the need for continued research to address the remaining challenges and improve diabetes care outcomes.

Unveiling ancestral threads: Exploring CCR5 ∆32 mutation frequencies in Colombian populations for HIV/AIDS therapeutics

AIDS remains a significant global health challenge since its emergence in 1981, with millions of deaths and new cases every year. The CCR5 ∆32 genetic deletion confers immunity to HIV infection by altering a cell membrane protein crucial for viral entry. Stem cell transplants from homozygous carriers of this mutation to HIV-infected individuals have resulted in viral load reduction and disease remission, suggesting a potential therapeutic avenue. This study aims to investigate the relationship between genetic ancestry and the frequency of the CCR5 ∆32 mutation in Colombian populations, exploring the feasibility of targeted donor searches based on ancestry composition. Utilizing genomic data from the CÓDIGO-Colombia consortium, comprising 532 individuals, the study assessed the presence of the CCR5 ∆32 mutation and examined if the population was on Hardy-Weinberg equilibrium. Individuals were stratified into clusters based on African, American, and European ancestry percentages, with logistic regression analysis performed to evaluate the association between ancestry and mutation frequency. Additionally, global genomic databases were utilized to visualize the worldwide distribution of the mutation. The findings revealed a significant positive association between European ancestry and the CCR5 ∆32 mutation frequency, underscoring its relevance in donor selection. African and American ancestry showed negative but non-significant associations with CCR5 ∆32 frequency, which may be attributed to the study's limitations. These results emphasize the potential importance of considering ancestry in donor selection strategies, reveal the scarcity of potential donors in Colombia, and underscore the need to consider donors from other populations with mainly European ancestry if the CCR5 ∆32 stem cell transplant becomes a routine treatment for HIV/AIDS in Colombia.

Innovative Strategies for Liver Transplantation: The Role of Mesenchymal Stem Cells and Their Cell-Free Derivatives.

Despite being the standard treatment for end-stage liver disease, liver transplantation has limitations like donor scarcity, high surgical costs, and immune rejection risks. Mesenchymal stem cells (MSCs) and their derivatives offer potential for liver regeneration and transplantation. MSCs, known for their multipotency, low immunogenicity, and ease of obtainability, can differentiate into hepatocyte-like cells and secrete bioactive factors that promote liver repair and reduce immune rejection. However, the clinical application of MSCs is limited by risks such as aberrant differentiation and low engraftment rates. As a safer alternative, MSC-derived secretomes and extracellular vesicles (EVs) offer promising therapeutic benefits, including enhanced graft survival, immunomodulation, and reduced ischemia-reperfusion injury. Current research highlights the efficacy of MSC-derived therapies in improving liver transplant outcomes, but further studies are necessary to standardize clinical applications. This review highlights the potential of MSCs and EVs to address key challenges in liver transplantation, paving the way for innovative therapeutic strategies.

Harnessing cellular therapeutics for type 1 diabetes mellitus: progress, challenges, and the road ahead.

Type 1 diabetes mellitus (T1DM) is a growing global health concern that affects approximately 8.5 million individuals worldwide. T1DM is characterized by an autoimmune destruction of pancreatic β cells, leading to a disruption in glucose homeostasis. Therapeutic intervention for T1DM requires a complex regimen of glycaemic monitoring and the administration of exogenous insulin to regulate blood glucose levels. Advances in continuous glucose monitoring and algorithm-driven insulin delivery devices have improved the quality of life of patients. Despite this, mimicking islet function and complex physiological feedback remains challenging. Pancreatic islet transplantation represents a potential functional cure for T1DM but is hindered by donor scarcity, variability in harvested cells, aggressive immunosuppressive regimens and suboptimal clinical outcomes. Current research is directed towards generating alternative cell sources, improving transplantation methods, and enhancing cell survival without chronic immunosuppression. This Review maps the progress in cell replacement therapies for T1DM and outlines the remaining challenges and future directions. We explore the state-of-the-art strategies for generating replenishable β cells, cell delivery technologies and local targeted immune modulation. Finally, we highlight relevant animal models and the regulatory aspects for advancing these technologies towards clinical deployment.

Heart Transplantation and Left Ventricular Assist Devices: Long-Term Prognosis and Effects on Mental Health.

Heart transplantation and left ventricular assist devices (LVADs) have emerged as crucial interventions for end-stage heart failure, dramatically improving patient outcomes. This narrative review examines their historical context, indications, procedures, and outcomes, as well as their impact on long-term survival, quality of life, functional status, and mental health. While heart transplantation remains the optimal treatment, donor scarcity limits its application. LVADs have become a viable alternative, either as a bridge to transplantation or as destination therapy. Both interventions demonstrate similar long-term survival rates and significant improvements in health-related quality of life and functional status. However, they present distinct long-term management challenges, including immunosuppression needs for transplant recipients and device-related issues for LVAD patients. Mental health effects are considerable, necessitating psychological support and adaptive coping strategies. Complications such as infection, bleeding, and thrombosis remain concerns for both interventions. Patient selection criteria, technological advancements, and long-term management strategies are critical factors in optimizing outcomes. Future research should focus on device miniaturization, enhanced biocompatibility, and less invasive insertion techniques to further advance these therapies and improve patient care in end-stage heart failure.

Pulmonary artery banding in infants and young children with end-stage left ventricular dilated cardiomyopathy-Cohort Study.

Dilated cardiomyopathy (DCM) is the most common cardiomyopathy and 40-50% patients may die or need heart transplant in 5 years after diagnosis. Although heart transplantation being the most effective life-saving option of end-stage DCM, scarcity of donors and series of complications prevent many patients from receiving timely treatment. Pulmonary artery banding (PAB) is recently described as an alternative strategy for end-stage DCM, with low left ventricular function (LVEF) but preserved right ventricular function, may potentially restore heart function and delay the need for heart transplantation, but current clinical evidence is still insufficient. On the other hand, the medication treatment of DCM in pediatric patients is mostly based on the experience of adults. It remains unclear whether PAB combing medication treatment could benefit infants and young children patients. The aim of this study was to assess the short-term efficacy of PAB combined with medication therapy in infants and young children with end stage DCM, comparing with medication therapy alone. This is a retrospective analysis of 18 consecutive pediatric patients aged ranging from 1 month to 44 months old who diagnosed with end-stage DCM (LVEF30%) with preserved right ventricular function between 2019 and 2023 in our hospital. All patients had been treated with conventional medications for two months. Then they were divided in two groups: PAB surgery group (6/18), and non-surgery group (12/18). Regardless of whether surgery was performed, both groups continued to receive medication treatment. Recovery of ventricular function was primary endpoints. Secondary endpoints included 180-day mortality and severe heart failure (LVEF≤30%). We found there were no differences in age, weight, height, BMI, renal function, liver function, pulmonary hypertension, tricuspid valve regurgitation, mitral valve regurgitation and genetic abnormalities between those with and without PAB surgery. Comparing with non-surgery group, 5 patients in surgery group regain the normal cardiac ejection fraction (LVEF≥50%) (5/6, 83.3% vs. 4/12, 33.3%, P=0.131). A total of 3 patients had sudden death in non-surgery group, and there was no death in surgery group (P=0.180). 5 patients (5/12, 41.7%) still remain the low heart failure (LVEF≤40%) after 6 months of enrollment only given medical therapy, and none of patients present with LVEF≤40% in PAB surgery group (0/6, 0% vs. 8/12, 67.7%, P=0.034). Pulmonary artery banding is safe and effective in infants and young children with end-stage DCM with preserved right ventricular function. Combined with conventional heart failure medication therapy, it may provide short-term benefits post-operatively, decrease the cardiogenic shock, and act as a bridge to recovery and potentially reduce the need for heart transplantation. Long-term effects remain further observation, and larger randomized controlled trials would be more persuasive in validating its efficacy.

Ethical considerations in lung re-transplantation.

Patients undergoing re-transplantation constitute a growing proportion of annual lung transplants. It is necessary to consider ethical considerations of re-transplantation in parallel with clinical progress. Most clinical data demonstrate patients undergoing re-transplantation have worse survival outcomes; however, there is limited discussion of the ethical principles surrounding re-transplantation. Ethical guidance in re-transplantation trails clinical advancement. The four-box model offers a valuable framework for assessing the ethical considerations in re-transplantation. This includes an analysis of medical indications, patient preferences, quality-of-life and contextual factors to support the ethical use of scarce donor lungs.

Islet transplantation in Korea.

Type 1 diabetes mellitus is characterized by absolute insulin deficiency, which requires life-long insulin replacement. Exogenous multiple-daily insulin injections are most commonly prescribed for patients with type 1 diabetes mellitus. However, exogenous insulin supply often fails to cope with real-time changing life-log variables, such as activity, diet and stress, which results in recurrent hypo- and hyperglycemia in patients with type 1 diabetes mellitus. Islet transplantation is an ideal method to treat patients with type 1 diabetes mellitus, as it can restore the endogenous capacity of glucose-stimulated insulin secretion. However, due to donor scarcity and technical barriers, only a limited number of islet transplantations have been carried out in Asia, including South Korea. Since 2013, our center has carried out two allogenic islet transplantations, with one case leading to near total insulin independence after one-to-one islet transplantation. Although the other patient failed to restore endogenous insulin production, there was a remarkable improvement in hypoglycemia. We speculate that islet transplantation remains an important and ideal treatment option for patients with type 1 diabetes mellitus who suffer from recurrent severe hypoglycemia.

Abstract We027: Gut Microbiota Modulation by Immunosuppression and Cardiac Cell Therapy in a Nonhuman Primate Ischemia/Reperfusion Model of Cardiac Regeneration

End-stage ischemic heart disease necessitates heart transplantation, and emerging cell therapy presents a promising solution to address donor scarcity. Disruption of gut microbiota significantly influences various diseases and treatments, including transplantation. However, the impact of immunosuppression and cardiac cell therapy on gut microbiota remains largely unexplored. To elucidate this relationship, we investigated gut microbiota dynamics in response to immunosuppression and cell therapy in a nonhuman primate (NHP) cardiac ischemia/reperfusion (IR) model, with controlled genetic, dietary, and environmental factors. Immunosuppression enriched anaerobes (Faecalibacterium, Streptococcus, Anaerovibrio, Dialister), increasing gut microbiota diversity. These changes correlated with metabolic shifts towards amino acid metabolism and nucleosides/nucleotides biosynthesis. Combined treatment of human induced pluripotent stem cell (iPSC)-derived endothelial cells (EC) and cardiomyocytes (CM) also increased gut microbiota diversity, with specific genera alterations. The EC/CM co-treatment group displayed gut microbiota resembling the pre-injury group, with host metabolism shifting towards amino acid and fatty acid/lipid biosynthesis post-cell therapy. These observed microbiota changes and metabolic shifts could serve as biomarkers for monitoring cell therapy and immunosuppression outcomes, offering potential therapeutic targets to enhance efficacy.

Partial Heart Transplantation Promotes Organ Stewardship: Domino Hearts and Split Roots

BackgroundPartial heart transplantation (PHT) has emerged as a pioneering approach for treating infants with irreparable heart valve dysfunction. However, the scarcity of suitable donors presents a significant bottleneck to its widespread application. This study introduces and evaluates the novel use of domino and split-root procedures within PHT. MethodsWe describe 6 pediatric cardiac patients who underwent either domino or split-root PHT at our institution. ResultsFrom May to August 2023, our team successfully executed 3 domino and 3 split-root PHTs, including 1 procedure that involved interinstitutional collaboration. These cases highlight the procedural feasibility and the potential for broader application. ConclusionsThe implementation of PHT represents a significant advance in pediatric heart care. Domino and split-root techniques within the PHT framework have the potential to substantially increase both donor availability and recipient capacity. These strategies usher in a new era of organ stewardship through addressing the challenge of donor organ shortage.

Preoperative Autologous Blood Donation for Rh-Negative Pregnant Women Undergoing Cesarean Sections.

Cesarean sections (C-section) often require blood transfusions in cases of severe bleeding, particularly challenging in Rh-negative pregnancies due to the scarcity of Rh-negative donors, with only approximately 0.3% of the population in Thailand. Autologous blood donation, where individuals donate their own blood before surgery, offers a promising solution. Our study focused on preparing preoperative autologous blood donations (PAD) for Rh-negative pregnancies. We conducted blood screening on 7,182 pregnancies at Takuapa Hospital from October 2013 to September 2018, identifying 21 Rh-negative pregnant women. We established criteria based on hemoglobin (Hb) levels, which are crucial for autologous blood preparation (Hb at 11.0 g/dL, and hematocrit (Hct) above 33%). Blood samples were collected twice during pregnancy, at 36 and 37 weeks, with the second collection 1 week before the C-section. Pregnancies testing positive for infectious markers were excluded following standard blood donation guidelines. Twelve pregnant women testing negative for infectious markers were enrolled. The demographic data showed 12 subjects aged 17 to 41 years, with an average of 27.83. Initial blood tests indicated Hb and Hct levels of 12.5 g/dL, and 36.4%, slightly decreasing to 12.2 g/dL and 35.8% in the second collection. On the day of the cesarean, levels further declined to 11.6 g/dL and 34.4%, respectively, within normal ranges. At discharge, the Hct measured 34.8%. Maternal and infant health post-C-section were good, with baby weights ranging from 2,640 to 4,080 g. None of the 12 cases required autologous blood transfusion, validating the safety of standard autologous blood preparation practices. This study highlights the safety of autologous blood donation for pregnant women with rare blood types, which was achieved through effective planning and collaboration among hospital departments. These findings can serve as a model for other hospitals and significantly reduce the burden of searching for Rh-negative donors.

Exploring Novel Treatment Modalities for Type 1 Diabetes Mellitus: Potential and Prospects.

Despite the effectiveness of insulin injections in managing hyperglycemia in type 1 diabetes mellitus (T1DM), they fall short in addressing autoimmunity and regenerating damaged islets. This review aims to explore the potential and prospects of emerging treatment modalities for T1DM, including mesenchymal stem cells (MSCs), MSC-derived exosomes, gene therapy, islet allotransplantation, pancreatic islet cell transplantation, and teplizumab. We review emerging treatment modalities for T1DM, highlighting several promising strategies with varied mechanisms and outcomes. Mesenchymal stem cells demonstrate potential in modulating the immune response and preserving or restoring beta-cell function, although variability in sources and administration routes necessitates further standardization. Similarly, MSC-derived exosomes show promise in promoting beta-cell regeneration and immune regulation, supported by early-stage studies showing improved glucose homeostasis in animal models, albeit with limited clinical data. Gene therapy, utilizing techniques like CRISPR-Cas9, offers targeted correction of genetic defects and immune modulation; however, challenges in precise delivery and ensuring long-term safety persist. Islet allotransplantation and pancreatic islet cell transplantation have achieved some success in restoring insulin independence, yet challenges such as donor scarcity and immunosuppression-related complications remain significant. Teplizumab, an anti-CD3 monoclonal antibody, has demonstrated potential in delaying T1DM onset by modulating immune responses and preserving beta-cell function, with clinical trials indicating prolonged insulin production capability. Despite significant progress, standardization, long-term efficacy, and safety continue to pose challenges across these modalities. Conclusion: While these therapies demonstrate significant potential, challenges persist. Future research should prioritize optimizing these treatments and validating them through extensive clinical trials to enhance T1DM management and improve patient outcomes.

Cardiac Xenotransplantation: A Narrative Review.

Cardiac xenotransplantation (cXT) has emerged as a solution to heart donor scarcity, prompting an exploration of its scientific, ethical, and regulatory facets. The review begins with genetic modifications enhancing pig hearts for human transplantation, navigating through immunological challenges, rejection mechanisms, and immune responses. Key areas include preclinical milestones, complement cascade roles, and genetic engineering to address hyperacute rejection. Physiological counterbalance systems, like human thrombomodulin and endothelial protein C receptor upregulation in porcine xenografts, highlight efforts for graft survival enhancement. Evaluating pig and baboon donors and challenges with non-human primates illuminates complexities in donor species selection. Ethical considerations, encompassing animal rights, welfare, and zoonotic disease risks, are critically examined in the cXT context. The review delves into immune control mechanisms with aggressive immunosuppression and clustered regularly interspaced palindromic repeats associated protein 9 (CRISPR/Cas9) technology, elucidating hyperacute rejection, complement activation, and antibody-mediated rejection intricacies. CRISPR/Cas9's role in creating pig endothelial cells expressing human inhibitor molecules is explored for rejection mitigation. Ethical and regulatory aspects emphasize the role of committees and international guidelines. A forward-looking perspective envisions precision medical genetics, artificial intelligence, and individualized heart cultivation within pigs as transformative elements in cXT's future is also explored. This comprehensive analysis offers insights for researchers, clinicians, and policymakers, addressing the current state, and future prospects of cXT.

Antibacterial sequential growth factor delivery from alginate/gelatin methacryloyl microspheres for bone regeneration

Autologous or allogeneic bone tissue grafts remain the mainstay of treatment for clinical bone defects. However, the risk of infection and donor scarcity in bone grafting pose challenges to the process. Therefore, the development of excellent biomaterial grafts is of great clinical importance for the repair of bone defects. In this study, we used gas-assisted microfluidics to construct double-cross-linked hydrogel microspheres with good biological function based on the ionic cross-linking of Cu2+ with alginate and photo-cross-linking of gelatin methacryloylamide (GelMA) by loading vascular endothelial growth factor (VEGF) and His-tagged bone morphogenetic protein-2 (BMP2) (AGMP@VEGF&BMP2). The Cu2+ component in the microspheres showed good antibacterial and drug-release behavior, whereas VEGF and BMP2 effectively promoted angiogenesis and bone tissue repair. In in vitro and in vivo experiments, the dual cross-linked hydrogel microspheres showed good biological function and biocompatibility. These results demonstrate that AGMP@VEGF&BMP2 microspheres could be used as a bone defect graft substitute to promote effective healing of bone defects and may be applied to other tissue engineering studies.

Bioorthogonal Delivery of Carbon Disulfide in Living Cells.

Carbon disulfide (CS2) is an environmental contaminant, which is deadly hazardous to the workers under chronic or acute exposure. However, the toxicity mechanisms of CS2 are still unclear due to the scarcity of biocompatible donors, which can release CS2 in cells. Here we developed the first bioorthogonal CS2 delivery system based on the "click-and-release" reactions between mesoionic 1,3-thiazolium-5-thiolates (TATs) and strained cyclooctyne exo-BCN-OH. We successfully realized intracellular CS2 release and investigated the causes of CS2-induced hepatotoxicity, including oxidative stress, proteotoxic stress and copper-dependent cell death. It is found that CS2 can be copper vehicles bypassing copper transporters after reacting with nucleophiles in cytoplasm, and extra copper supplementation will exacerbate the loss of homeostasis of cells and ultimately cell death. These findings inspired us to explore the anticancer activity of CS2 in combination with copper by introducing a copper chelating group in our CS2 delivery system.

Bioorthogonal Delivery of Carbon Disulfide in Living Cells

AbstractCarbon disulfide (CS2) is an environmental contaminant, which is deadly hazardous to the workers under chronic or acute exposure. However, the toxicity mechanisms of CS2 are still unclear due to the scarcity of biocompatible donors, which can release CS2 in cells. Here we developed the first bioorthogonal CS2 delivery system based on the “click‐and‐release” reactions between mesoionic 1,3‐thiazolium‐5‐thiolates (TATs) and strained cyclooctyne exo‐BCN‐OH. We successfully realized intracellular CS2 release and investigated the causes of CS2‐induced hepatotoxicity, including oxidative stress, proteotoxic stress and copper‐dependent cell death. It is found that CS2 can be copper vehicles bypassing copper transporters after reacting with nucleophiles in cytoplasm, and extra copper supplementation will exacerbate the loss of homeostasis of cells and ultimately cell death. These findings inspired us to explore the anticancer activity of CS2 in combination with copper by introducing a copper chelating group in our CS2 delivery system.

Detection of inflammasome activation in liver tissue during the donation process as potential biomarker for liver transplantation

Deceased donor liver transplantation (LT) is a crucial lifesaving option for patients with end-stage liver diseases. Although donation after brain death (DBD) remains the main source of donated organs, exploration of donation after circulatory death (DCD) addresses donor scarcity but introduces challenges due to warm ischemia. While technical advances have improved outcomes, challenges persist, with a 13% mortality rate within the first year. Delving into liver transplantation complexities reveals the profound impact of molecular signaling on organ fate. NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation play a pivotal role, influencing inflammatory responses. The NLRP3 inflammasome, found in hepatocytes, contributes to inflammation, fibrosis, and liver cell death. This study explores these dynamics, shedding light on potential biomarkers and therapeutic targets. Samples from 36 liver transplant patients were analyzed for ASC specks detection and inflammasome-related gene expression. Liver biopsies, obtained before and after cold ischemia storage, were processed for immunofluorescence, qRT-PCR, and Western blot. One year post-LT clinical follow-up included diagnostic procedures for complications, and global survival was assessed. Immunofluorescence detected activated inflammasome complexes in fixed liver tissues. ASC specks were identified in hepatocytes, showing a trend toward more specks in DCD livers. Likewise, inflammasome-related gene expression analysis indicated higher expression in DCD livers, decreasing after cold ischemia. Similar results were found at protein level. Patients with increased ASC specks staining exhibited lower overall survival rates, correlating with IL1B expression after cold ischemia. Although preliminary, these findings offer novel insights into utilizing direct detection of inflammasome activation in liver tissue as a biomarker. They suggest its potential impact on post-transplant outcomes, potentially paving the way for improved diagnostic approaches and personalized treatment strategies in LT.

Corneal thickness and endothelial change after use of ocular hypotensive agents.

Corneal transplantation can restore visual function when visual impairment is caused by a corneal disease. However, this treatment is associated with the scarcity of cornea donors. The suitability of corneal donation from patients with glaucoma using ocular hypotensive agents (OHAs) is controversial. This study aimed to elucidate changes in corneal thickness, corneal endothelial cell density, and corneal endothelial cell hexagonality after OHA use in patients with primary open-angle glaucoma. We retrospectively reviewed the data of 53 glaucoma suspect eyes without OHA use and 106 primary open-angle glaucoma eyes under OHA use. All participants underwent corneal parameter assessment using SP-3000P (Topcon Corp., Tokyo, Japan) at the time of diagnosis and the final visit. The OHA dose and timing of use were recorded. The ocular hypotensive agents score (OHAS) was determined based on the number, formula, frequency, and duration of OHA use. Baseline data showed no significant differences between the two groups with and without OHA use. At the final visit, the OHA-treated group showed significantly lower corneal thickness and corneal endothelial cell density than those of the control group. A weak positive correlation between the OHAS and changes in corneal endothelial cell hexagonality was noted. However, no correlation was observed between the OHAS and changes in corneal thickness or endothelial cell density. In conclusion, patients with glaucoma and using OHAs should undergo the corneal structural properties examinations before donation to ensure the quality of donor cornea.