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Frontiers in Immunology 2024The interaction between pyroptosis-a form of programmed cell death-and tumor immunity represents a burgeoning field of interest. Pyroptosis exhibits a dual role in... (Review)
Review
BACKGROUND
The interaction between pyroptosis-a form of programmed cell death-and tumor immunity represents a burgeoning field of interest. Pyroptosis exhibits a dual role in cancer: it can both promote tumor development and counteract it by activating immune responses that inhibit tumor evasion and encourage cell death. Current tumor immunotherapy strategies, notably CAR-T cell therapy and immune checkpoint inhibitors (ICIs), alongside the potential of certain traditional Chinese medicinal compounds, highlight the intricate relationship between pyroptosis and cancer immunity. As research delves deeper into pyroptosis mechanisms within tumor therapy, its application in enhancing tumor immune responses emerges as a novel research avenue.
PURPOSE
This review aims to elucidate the mechanisms underlying pyroptosis, its impact on tumor biology, and the advancements in tumor immunotherapy research.
METHODS
A comprehensive literature review was conducted across PubMed, Embase, CNKI, and Wanfang Database from the inception of the study until August 22, 2023. The search employed keywords such as "pyroptosis", "cancer", "tumor", "mechanism", "immunity", "gasdermin", "ICB", "CAR-T", "PD-1", "PD-L1", "herbal medicine", "botanical medicine", "Chinese medicine", "traditional Chinese medicine", "immunotherapy", linked by AND/OR, to capture the latest findings in pyroptosis and tumor immunotherapy.
RESULTS
Pyroptosis is governed by a complex mechanism, with the Gasdermin family playing a pivotal role. While promising for tumor immunotherapy application, research into pyroptosis's effect on tumor immunity is still evolving. Notably, certain traditional Chinese medicine ingredients have been identified as potential pyroptosis inducers, meriting further exploration.
CONCLUSION
This review consolidates current knowledge on pyroptosis's role in tumor immunotherapy. It reveals pyroptosis as a beneficial factor in the immunotherapeutic landscape, suggesting that leveraging pyroptosis for developing novel cancer treatment strategies, including those involving traditional Chinese medicine, represents a forward-looking approach in oncology.
PubMed: 38947336
DOI: 10.3389/fimmu.2024.1381778 -
Research Square Jun 2024Static cold storage of donor livers at 4°C incompletely arrests metabolism, ultimately leading to decreases in ATP levels, oxidative stress, cell death, and organ...
Static cold storage of donor livers at 4°C incompletely arrests metabolism, ultimately leading to decreases in ATP levels, oxidative stress, cell death, and organ failure. Hydrogen Sulfide (H S) is an endogenously produced gas, previously demonstrated to reduce oxidative stress, reduce ATP depletion, and protect from ischemia and reperfusion injury. H S is difficult to administer due to its rapid release curve, resulting in cellular death at high concentrations. AP39, a mitochondrially targeted, slow-release H S donor, has been shown to reduce ischemia-reperfusion injury in hearts and kidneys. Thus, we investigated whether the addition of AP39 during 3-day static cold storage can improve liver graft viability. At the end of storage, livers underwent six hours of acellular normothermic machine perfusion, a model of transplantation. During simulated transplantation, livers stored with AP39 showed reduced resistance, reduced cellular damage (ALT and AST), and reduced apoptosis. Additionally, bile production and glucose, as well as energy charge were improved by the addition of AP39. These results indicate that AP39 supplementation improves liver viability during static cold storage.
PubMed: 38947096
DOI: 10.21203/rs.3.rs-4487319/v1 -
World Journal of Gastroenterology Jun 2024In this editorial we comment on the article published in a recent issue of the . Acute liver failure (ALF) is a critical condition characterized by rapid hepatocellular... (Review)
Review
In this editorial we comment on the article published in a recent issue of the . Acute liver failure (ALF) is a critical condition characterized by rapid hepatocellular injury and organ dysfunction, and it often necessitates liver transplant to ensure patient survival. Recent research has elucidated the involvement of distinct cell death pathways, namely ferroptosis and pyroptosis, in the pathogenesis of ALF. Ferroptosis is driven by iron-dependent lipid peroxidation, whereas pyroptosis is an inflammatory form of cell death; both pathways contribute to hepatocyte death and exacerbate tissue damage. This comprehensive review explores the interplay between ferroptosis and pyroptosis in ALF, highlighting the role of key regulators such as silent information regulator sirtuin 1. Insights from clinical and preclinical studies provide valuable perspectives on the dysregulation of cell death pathways in ALF and the therapeutic potential of targeting these pathways. Collaboration across multiple disciplines is essential for translating the experimental insights into effective treatments for this life-threatening condition.
Topics: Humans; Liver Failure, Acute; Ferroptosis; Pyroptosis; Hepatocytes; Animals; Sirtuin 1; Signal Transduction; Liver; Lipid Peroxidation; Liver Transplantation; Iron
PubMed: 38946877
DOI: 10.3748/wjg.v30.i23.2931 -
Precision Clinical Medicine Jun 2024Myeloid differentiation factor 88 (MyD88) is the core adaptor for Toll-like receptors defending against microbial invasion and initiating a downstream immune response...
BACKGROUND
Myeloid differentiation factor 88 (MyD88) is the core adaptor for Toll-like receptors defending against microbial invasion and initiating a downstream immune response during microbiota-host interaction. However, the role of MyD88 in the pathogenesis of inflammatory bowel disease is controversial. This study aims to investigate the impact of MyD88 on intestinal inflammation and the underlying mechanism.
METHODS
MyD88 knockout (MyD88) mice and the MyD88 inhibitor (TJ-M2010-5) were used to investigate the impact of MyD88 on acute dextran sodium sulfate (DSS)-induced colitis. Disease activity index, colon length, histological score, and inflammatory cytokines were examined to evaluate the severity of colitis. RNA transcriptome analysis and 16S rDNA sequencing were used to detect the potential mechanism.
RESULTS
In an acute DSS-colitis model, the severity of colitis was not alleviated in MyD88 mice and TJ-M2010-5-treated mice, despite significantly lower levels of NF-κB activation being exhibited compared to control mice. Meanwhile, 16S rDNA sequencing and RNA transcriptome analysis revealed a higher abundance of intestinal and an up-regulation of the nucleotide oligomerization domain-like receptors (NLRs) signaling pathway in colitis mice following MyD88 suppression. Further blockade of the NLRs signaling pathway or elimination of gut microbiota with broad-spectrum antibiotics in DSS-induced colitis mice treated with TJ-M2010-5 ameliorated the disease severity, which was not improved solely by MyD88 inhibition. After treatment with broad-spectrum antibiotics, downregulation of the NLR signaling pathway was observed.
CONCLUSION
Our study suggests that the suppression of MyD88 might be associated with unfavorable changes in the composition of gut microbiota, leading to NLR-mediated immune activation and intestinal inflammation.
PubMed: 38946731
DOI: 10.1093/pcmedi/pbae013 -
The Medical Journal of Australia Jul 2024To assess differences between Aboriginal and Torres Strait Islander and non-Indigenous Australian children and young adults in access to and outcomes of kidney...
OBJECTIVES
To assess differences between Aboriginal and Torres Strait Islander and non-Indigenous Australian children and young adults in access to and outcomes of kidney transplantation.
STUDY DESIGN
A cohort study based on prospectively collected data; analysis of Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) data.
SETTING, PARTICIPANTS
Children and young adults aged 0-24 years who commenced kidney replacement therapy in Australia during 1963-2020.
MAIN OUTCOME MEASURES
Proportions of children and young adults who received kidney transplants within five years of commencing dialysis; 5- and 10-year death-censored graft survival; and 5- and 10-year survival of children and young adults who received kidney transplants or who remained on dialysis.
RESULTS
During 1963-2020, 3736 children and young adults received kidney replacement therapy in Australia: 213 (5.8%) Aboriginal and Torres Strait Islander and 3523 (94.2%) non-Indigenous children and young adults. During follow-up (median, eight years; interquartile range [IQR], 2.6-15 years), 2762 children and young adults received kidney transplants: 93 Aboriginal and Torres Strait Islander (43.7% of those receiving kidney replacement therapy) and 2669 non-Indigenous children and young adults (75.8%). Smaller proportions of Aboriginal and Torres Strait Islander than of non-Indigenous children and young adults received transplants within five years of commencing dialysis (99, 46% v 2924, 83.0%), received living donor transplants (19, 20% v 1170, 43.9%), or underwent pre-emptive transplantation (one, 1.1% v 363, 13.6%). Five-year graft survival for Aboriginal and Torres Strait Islander recipients was similar to non-Indigenous recipients (61% v 75%; adjusted hazard ratio [aHR], 1.43; 95% confidence interval [CI], 0.02-2.05), but 10-year graft survival was lower (35% v 61%; aHR, 1.69; 95% CI, 1.25-2.28). Five- and 10-year survival after kidney transplantation was similar for Aboriginal and Torres Strait Islander and non-Indigenous people. Among those who remained on dialysis, 10-year survival was poorer for Aboriginal and Torres Strait Islander than non-Indigenous children and young adults (aHR, 1.50; 95% CI, 1.08-2.10).
CONCLUSIONS
Five-year graft and recipient survival were excellent for Aboriginal and Torres Strait Islander children and young adults who received kidney transplants; however, a lower proportion received transplants within five years of dialysis initiation, than non-Indigenous children and young adults. Improving transplant access within five years of dialysis commencement should be a priority.
Topics: Humans; Kidney Transplantation; Native Hawaiian or Other Pacific Islander; Australia; Adolescent; Young Adult; Child; Registries; Female; Male; Child, Preschool; Infant; Graft Survival; Health Services Accessibility; Kidney Failure, Chronic; New Zealand; Infant, Newborn; Renal Dialysis; Cohort Studies; Australian Aboriginal and Torres Strait Islander Peoples
PubMed: 38946656
DOI: 10.5694/mja2.52355 -
Clinical and Molecular Hepatology Jul 2024Hepatic ischemia‒reperfusion injury (HIRI) is a common and inevitable complication of hepatic trauma, liver resection, or liver transplantation. It contributes to... (Review)
Review
Hepatic ischemia‒reperfusion injury (HIRI) is a common and inevitable complication of hepatic trauma, liver resection, or liver transplantation. It contributes to postoperative organ failure or tissue rejection, eventually affecting patient prognosis and overall survival. The pathological mechanism of HIRI is highly complex and has not yet been fully elucidated. The proposed underlying mechanisms include mitochondrial damage, oxidative stress imbalance, abnormal cell death, immune cell hyperactivation, intracellular inflammatory disorders and other complex events. In addition to serious clinical limitations, available antagonistic drugs and specific treatment regimens are still lacking. Therefore, there is an urgent need to not only clarify the exact etiology of HIRI but also reveal the possible reactions and bottlenecks of existing drugs, helping to reduce morbidity and shorten hospitalizations. We analyzed the possible underlying mechanism of HIRI, discussed various outcomes among different animal models and explored neglected potential therapeutic strategies for HIRI treatment. By thoroughly reviewing and analyzing the literature on HIRI, we gained a comprehensive understanding of the current research status in related fields and identified valuable references for future clinical and scientific investigations.
PubMed: 38946464
DOI: 10.3350/cmh.2024.0222 -
Medical Science Monitor : International... Jul 2024BACKGROUND Thrombosis poses a grave threat to patients undergoing kidney transplants, with a heightened risk of mortality. While previous studies have established a link...
BACKGROUND Thrombosis poses a grave threat to patients undergoing kidney transplants, with a heightened risk of mortality. While previous studies have established a link between COVID-19 and thrombosis, the specific association between COVID-19 and thrombosis in this patient population remains unexplored. MATERIAL AND METHODS We conducted a retrospective analysis utilizing data from 394 individuals who underwent kidney transplantation within the period of September 1, 2015, to April 1, 2023. To evaluate overall survival, we employed Kaplan-Meier analysis and utilized a logistic regression model for risk analysis. Furthermore, we developed a prediction model and assessed its accuracy through calibration curves. RESULTS Out of the 394 patients included in our study, a total of 51 individuals experienced thrombosis, resulting in 2 deaths. Our analysis revealed that COVID-19 infection significantly increased the risk of thrombosis (odds ratio [OR] 8.60, 95% confidence interval 3.13-24.74, P<0.01). Additionally, the use of cyclosporine was found to elevate the risk of death (OR 20.86, 95% CI 7.93-59.24, P<0.01) according to multifactorial analysis. Logistic models were employed to screen variables, and predictive models were constructed based on the presence of COVID-19 infection and the usage of cyclosporine. A nomogram was developed, demonstrating promising accuracy in estimating the risk of thrombosis during internal validation, with a corrected C-index of 0.869. CONCLUSIONS Our study suggests that both COVID-19 infection and the use of cyclosporine can serve as reliable predictors of thrombosis risk in patients undergoing renal transplantation. Furthermore, we developed a mortality risk prediction model based on COVID-19 in assessing thrombosis.
Topics: Humans; Kidney Transplantation; COVID-19; Thrombosis; Male; Female; Middle Aged; Retrospective Studies; Incidence; Adult; Prognosis; Risk Factors; Transplant Recipients; SARS-CoV-2; Logistic Models; Aged; Cyclosporine; Kaplan-Meier Estimate
PubMed: 38946121
DOI: 10.12659/MSM.944285 -
Transplantation Jul 2024Antibody-mediated rejection (AMR) is a major cause of renal allograft dysfunction and loss. Targeting B cells and/or donor-specific antibody removal using plasma...
BACKGROUND
Antibody-mediated rejection (AMR) is a major cause of renal allograft dysfunction and loss. Targeting B cells and/or donor-specific antibody removal using plasma exchange and anti-CD20 antibodies are increasingly used in clinical practice, but the efficacy remains limited. Recent studies suggest that targeting purinergic P2X7 receptor/ATP axis can have profound immune regulatory effects in transplant models, but the mechanisms involved remain incompletely defined.
METHODS
Purified B cells were isolated from the spleen of Balb/C mice and cultured with oxidized ATP at different concentrations. Proliferation and differentiation of B cells were examined. Effects of oxidized ATP were examined in a presensitized animal model where kidney allograft rejection mimics aspects of clinical AMR. Histopathology was assessed at the time of rejection or on day 5 after kidney transplantation. Infiltrating immune cells in renal allografts were detected by flow cytometry.
RESULTS
Oxidized ATP inhibited B-cell activation and proliferation in vitro, significantly attenuated histological signs of graft injury and prolonged kidney allograft survival. Mechanistically, oxidized ATP inhibited antibody secretion by activated B cells in response to lipopolysaccharide stimulation and markedly suppressed the production of donor-specific antibody in kidney allograft recipients. Oxidized ATP also reduced graft infiltration by other inflammatory cells.
CONCLUSIONS
These findings provide evidence for the involvement of the purinergic P2X7 receptor pathway in AMR and suggest that targeting this pathways may have important clinical implications.
PubMed: 38946027
DOI: 10.1097/TP.0000000000005118 -
Clinics in Liver Disease Aug 2024Portopulmonary hypertension (POPH), hepatopulmonary syndrome, and hepatic hydrothorax constitute significant complications of portal hypertension, with important... (Review)
Review
Portopulmonary hypertension (POPH), hepatopulmonary syndrome, and hepatic hydrothorax constitute significant complications of portal hypertension, with important implications for management and liver transplantation (LT) candidacy. POPH is characterized by obstruction and remodeling of the pulmonary resistance arterial bed. Hepatopulmonary syndrome is the most common pulmonary vascular disorder, characterized by intrapulmonary vascular dilatations causing impaired gas exchange. LT may improve prognosis in select patients with POPH. LT is the only effective treatment of hepatopulmonary syndrome. Hepatic hydrothorax is defined as transudative pleural fluid accumulation that is not explained by primary cardiopulmonary or pleural disease. LT is the definitive cure for hepatic hydrothorax.
Topics: Humans; Hypertension, Portal; Hepatopulmonary Syndrome; Hydrothorax; Hypertension, Pulmonary; Liver Transplantation
PubMed: 38945638
DOI: 10.1016/j.cld.2024.03.005 -
Clinics in Liver Disease Aug 2024Interventions for portal hypertension are continuously evolving and expanding beyond the realm of medical management. When complications such as varices and ascites... (Review)
Review
Interventions for portal hypertension are continuously evolving and expanding beyond the realm of medical management. When complications such as varices and ascites persist despite conservative interventions, procedures including transjugular intrahepatic portosystemic shunt creation, transvenous obliteration, portal vein recanalization, splenic artery embolization, surgical shunt creation, and devascularization are all potential interventions detailed in this article. Selection of the optimal procedure to address the underlying cause, treat symptoms, and, in some cases, bridge to liver transplantation depends on the specific etiology of portal hypertension and the patient's comorbidities.
Topics: Humans; Hypertension, Portal; Portasystemic Shunt, Transjugular Intrahepatic; Embolization, Therapeutic; Portal Vein; Esophageal and Gastric Varices; Splenic Artery; Portasystemic Shunt, Surgical; Liver Transplantation
PubMed: 38945636
DOI: 10.1016/j.cld.2024.03.003