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关键词： aCSF   artificial cerebrospinal fluid   Arc   activity-regulated cytoskeletal gene   BDNF   brain-derived neurotrophic factor   Bdnf   brain-derived neurotrophic factor gene   BLA   basolateral amygdala   C57BL/6NHsd   a strain of black mice used for stress testing   CA   1   Cornu Ammonis 1   CC   cage control   CD1   Hsd:ICR retired breeder mice used as aggressors   CD11b   Intergrin alpha M   CeA   central amygdala   cEPo   carbamoylated erythropoietin   CR   conditioned response   CS   conditioned stimulus   Creb1   cAMP responsive element binding protein 1 gene   CS   cEPo-treated Stay mice   ΔCt   difference between target gene value of corresponding endogenous reference gene   ΔΔCt   fold change of target gene expression relative to reference sample, normalized to reference gene   CR   cued response   DG   Dentate Gyrus   EC. Escape cEPo-treated   Egr1   early growth response gene 1   EPo   erythropoietin   EpoR   erythropoietin receptor   Epor   erythropoietin receptor gene   EV   Escape Vehicle-treated   g   gram(s)   ga   gauge   Gapdh   housekeeping gene   GFAP   glial fibrillary acidic protein gene   Hcrtr1   Orexin receptor 1 gene   Hcrtr2   Orexin receptor 2 gene   icv   intracerebroventricular   iDG   single intra-dentate gyrus   NIH   National Institutes of Health   NIMH   National Institute of Mental Health   PBS   phosphate buffer solution   PTSD   post-traumatic stress disorder   s   seconds   SAM   Stress Alternatives Model   SC   Stay cEPO-treated   SIP   Social Interaction Preference   SV   Stay Vehicle-treated   SVZ   subventricular zone   TNF   α   tumor necrosis factor alpha   US   unconditioned stimulus  

摘要： The hormone and trophic factor Erythropoietin (EPo) promotes red blood cell production and has neurotrophic effects, modulating behavior and promoting neural plasticity, like neurogenesis. Modifying EPo by attaching a carbamoyl group (cEPo) results in similar neuronal effects without erythropoietic actions. We hypothesize that neuroplastic and learning effects of cEPo may be dependent on its action in dorsal dentate gyrus of the hippo-campus, where neurogenesis occurs. The Stress Alternatives Model (SAM) is a 4-day social stress and decision-making paradigm with a large novel aggressor that provides opportunities to avoid interaction via escape routes. Early, male test mice display stable Escape (avoiding aggression) or Stay (acquiescence to aggressor) behavioral phenotypes. In these studies, mice were given a single intracerebroventricular (icv;100 ng), or single intra-dentate gyrus (iDG;10 ng) injection of cEPo or vehicle. By Day 4, 30% of icv cEPo treated mice and 37.5% of iDG cEPo treated mice reversed their phenotype (Stay to Escape). Mice receiving vehicle injections did not change. Normalization of social preference, and reduction in fear freezing behavior, after cEPo treatment, coincide with transcriptional changes of orexin receptors (Hcrtr1 & Hcrtr2) in the hippocampus, including phenotype-and treatment-dependent alterations in learning-associated molecular signaling molecules. Hippocampal Hcrtr1 moderately colocalize with EPo receptors (Epor) in the dentate gyrus, while Hcrtr2 is expressed with Epor in CA1. Anxiolytic actions of cEPo during social interaction indicate mechanisms that influence learning in stressful situations, suggesting that cEPo may be a novel agent for treatment of comorbid conditions related to anxiety, depression, and PTSD.

关键词： Gut-brain axis   Neuroinflammation   Depression   Glial cells   Gut microbiota   TCM   4EP   4-Ethylphenol   4EPS   4-Ethylphenyl sulfate   5-HT   Serotonin   5-HTP   5-hydroxytryptophan   AHR   Aryl hydrocarbon receptor   Arc   Activity-regulated cytoskeleton-associated protein   BBB   Blood-brain barrier   BCAAs   Branched-chain amino acids   BDNF   Brain-derived neurotrophic factor   BED47   2,2′,4,4,4-tetrabromodiphenyl ether   CD   Cluster of Differentiation   CMS   Chronic mild stress   CNS   Central nervous syst   CORT   Corticosterone   COX   Cyclooxygenase   CRS   Chronic restraint stress   CSDS   Chronic social defeat stress   CTS   Cryptotanshinone   CUMS   Chronic unpredictable mild stress   CUS   Chronic unpredictable stress   DA   Dopamine   FGF-2   fibroblast growth factor-2   FGFR1   FGF receptor 1   GABA   Gamma-aminobutyric acid   GF   Germ-free   GFAP   Glial fibrillary acidic protein   GI   Gastrointestinal   HDACs   Histone deacetylases   HMGB1   High mobility group box chromosomal protein 1   HO-1   Heme oxygenase-1   HPA   Hypothalamic-pituitary-adrenal   HT-22 cells   Hippocampal neuronal cells   Iba-1   Ionized calcium binding adapter molecule 1   ICH   Intracerebral Hemorrhage   IDO   Indoleamine 2,3-dioxygenase   IFN   Interferon   IGF-1   Insulin-like growth factor 1   IL   Inte Jujuboside A rleukin   INOS   Inducible Nitric Oxide Synthase   JuA   Jujuboside A   KMO   Kynurenine 3-monooxygenase   LPS   Lipopolysaccharide   MAMPs   Microbe-associated molecular patterns   MAPK   Mitogen-activated protein kinase   MDA   Malondialdehyde   MDD   Major depressive disorder   Mfn2   Mitofusion 2   MOOs   Morinda officinalis oligosaccharides   mPFC   medial Prefrontal cortex   MRI   Magnetic Resonance Imaging   MRS   Mother-infant separation combined with restraint stress   NF-?B   Nuclear Factor-?B   NLRP3   NOD-like receptor protein 3   NLRs   NOD-like receptors   NO   Nitrogen monoxide   NOD   Nucleotide-binding oligomerization domain   Nrf2   Nuclear transcription factor E2-related factor 2   OTU   Operational taxonomic unit   OVX   Ovariectomy   PDGF   Platelet-derived growth factor   PFC   Prefrontal cortex   PGE2   Prostaglandin E2   PPS   Poria cocos polysaccharide   PRRs   Pattern recognition receptors   PSD   Post stroke depression   PSD95   Protein Pos  

摘要： Background Depression is characterized by low mood, cognitive slowing and a tendency to self-harm, and has a complex etiology involving abnormalities in neuromodulation ( e.g ., monoamine transmitter imbalance and reduced neuroplasticity). Gut-brain axis studies have shown that dysregulation of gut flora can trigger neuroinflammation and impair glial cell function, leading to depression. Modulation of flora-glial cell interactions and their pharmacological mechanisms is key to treatment. Purpose This review discusses the new discovery of the interaction mechanism between glial cells and gut microflora in depression models, providing new targets and directions for the treatment of TCM in depression. Further bridging the gap in current research on the gut-brain axis in depression. Method Literature was searched, analyzed, and collected using PubMed, Web of Science, and China National Knowledge Infrastructure. The search terms used were " gut-brain axis ", " neuroinflammation ", " depression ", " glial cells ", " Gut microbiota "," TCM ", etc. Several combinations of these keywords were used. Studies using models of depression were used. Results During the literature screening process, a total of 1685 records were initially retrieved from databases. After removing duplicates (1068) and other ineligible records (200), 417 articles underwent title and abstract screening, with 134 excluded. Further full-text assessment of 283 articles led to the inclusion of 149 new studies. Reasons for exclusion included mismatched outcomes (8), ineligible experimental models (12), among others. Combined with 14 previously included studies, the final review comprised 163 articles (See Figure 1). The dialog mechanism between gut microflora and glial cells plays an important role in the pathogenesis of depression. In addition, there are a variety of herbal active ingredients and herbal formulas that can significantly affect the composition of the gut flora and glial cell activation in depr

关键词： Hepcidin   Dog   Portosystemic shunt   Anaemia of chronic disease   ALKP   alkaline phosphatase   ALT   alanin-aminotransferase   CRP   C-reactive protein   EDTA   ethylenediaminetetraacetic acid   ELISA   enzyme-linked immunosorbent assay   HE   hepatoencephalopathy   IL   interleukin   IPSS   intrahepatic portosystemic shunt   LC/MS-MS   Liquid chromatography tandem mass spectrometry   MCH   mean corpuscular haemoglobin   MCV   mean corpuscular volume   NH3   ammonia   PSS   portosystemic shunt   SPE   solid-phase extraction   TNF   tumor necrosis factor  

摘要： Microcytosis and iron sequestration are commonly observed abnormalities in dogs with portosystemic shunt (PSS). The role of hepcidin – the main hormone regulating iron homeostasis – in this condition is still unclear. Our study is intended to determine the serum concentrations of known hepcidin isomers in canine patients with portosystemic shunt, compared to a healthy control group. Routine haematological and biochemical examinations were performed for 10 dogs diagnosed with PSS and for 18 healthy controls. And the serum concentrations of hepcidin-α and hepcidin-β isomers were determined by liquid chromatography-tandem mass spectrometry (LC/MS-MS) method. In this study, both serum hepcidin isomer concentrations were significantly ( p  < 0,05) higher in the PSS group compared to healthy dogs (hepcidin-α: 46.1 vs. 23.1 ng·mL −1 , p  = 0.014, hepcidin-β: 76.6 vs 48.4 ng·mL −1 , p  = 0.027). In dogs with PSS, there was a significant negative correlation between iron and hepcidin isomer concentrations (hepcidin-α: rho: −0.81, p  = 0.007, hepcidin-β rho: −0.84, p  = 0.0004). Our results suggest that elevated serum hepcidin concentration plays an important role in the development of microcytosis and iron sequestration observed in patients with PSS; however, further studies needed in large cohort of patients. Serum hepcidin could be used as a potential biomarker in patients with PSS-associated anaemia.

关键词： Alcohol   Microbiome   Gut-liver axis   Gut-brain axis   Neuroinflammation   ADH   Alcohol dehydrogenase   AUD   alcohol use disorder   ALD   alcohol-associated liver disease   ABD   alcohol-related brain damage   ALDH2   aldehyde dehydrogenase 2   ADRD   Alzheimer's disease and related dementias   AMPs   antimicrobial peptides   BBB   blood-brain barrier   CYP2E1   cytochrome P450-2E1   DCs   dendritic cells   EAE   experimental autoimmune encephalomyelitis   FMT   fecal microbiota transplantation   GI   gastrointestinal   GAPs   goblet cell-associated antigen passages   ILC3   group 3 innate lymphoid cells   IL   interleukin   KO   knockout   MEOS   microsomal ethanol-oxidizing system   MUC2   Mucin-2   mAChR4   muscarinic ACh receptor 4   NADPH   nicotinamide adenine dinucleotide phosphate   NAD   nicotinamide adenine dinucleotide   NK   natural killer   NLRP3   NOD-like receptor protein 3   NF-κB   nuclear factor kappa B   PAMP   pathogen-associated molecular pattern   PUFAs   polyunsaturated fatty acids   ROS   reactive oxygen species   Reg3   regenerating antimicrobial peptides   RA   rheumatoid arthritis   SASP   senescence-associated secretory phenotype   SCFAs   short-chain fatty acids   SIRT1   silent information regulator 1   TNF-α   tumor necrosis factor-alpha   WT   wild-type  

摘要： Alcohol consumption exerts complex, dose- and context-dependent effects on human health, particularly by influencing the gut microbiome, intestinal barrier integrity, immune regulation, and aging processes. Genetic variation and advancing age are two major, and often interacting, factors that modify the risk of alcohol-related diseases. Among genetic factors, the prevalent aldehyde dehydrogenase 2 polymorphism (ALDH2∗2) compromises acetaldehyde clearance, driving toxic metabolite accumulation, oxidative stress, and increased intestinal permeability that disrupts gut microbial communities, even at low levels of alcohol consumption. Heavy and chronic alcohol use further disrupts gut microbial communities, erodes mucosal integrity, and drives systemic inflammation, contributing to alcohol-associated liver disease (ALD), neuroinflammation, and multi-organ injury. Aging independently worsens these effects by promoting chronic low-grade inflammation and impaired immune responses, heightening susceptibility to alcohol-induced pathology. In specific contexts, such as certain autoimmune diseases, low to moderate alcohol intake may exert immunomodulatory effects and influence the gut microbiome, potentially contributing to reduced inflammation and alterations in microbial composition. This review synthesizes current mechanistic insights into how alcohol, host genetics, the gut microbiome, immune regulatory pathways, and aging intersect to influence disease risk. As global populations age and the burden of alcohol-related health issues rises, there is an urgent need for integrated, systems-level approaches. Future research should prioritize precision-based, gut-targeted strategies aimed at restoring microbial balance, maintaining intestinal barrier integrity, and mitigating alcohol-related harm across the lifespan.

关键词： Immune escape   Immunotherapy   Major histocompatibility complex (MHC) class I   Prostate cancer   Treatment  

摘要： Cancers such as prostate cancer (PC) disproportionately impact middle-aged men (those between the ages of 45 and 60) and are a significant cause of male death worldwide. In treating PC, immunotherapy has a limited role despite its revolutionary impact on cancer care for many tumor types. Immune evasion, in which tumor cells evade detection and destruction by CD8 + cytotoxic T lymphocytes (CTLs), is an essential component in PC growth. Because of this lapse in immune monitoring, cancers can proliferate and disseminate. For CTLs to effectively recognize and eliminate tumor-associated antigens, stable and surface-localized expression of major histocompatibility complex class I (MHC-I) is critical. Furthermore, cancer cells often exhibit immune escape mechanisms that attempt to evade T-cell identification, such as reducing or eliminating tumor MHC-I expression. Immunotherapy for cancer, including the use of antibodies that target immunological checkpoint molecules, has a worse chance of success due to tumor immune escape. Another interesting finding is the presence of tumor-infiltrating cells in PC, which indicates that the immune system does not disregard PC. In this review, we reviewed its impact on different types of cancer and the ability of cancer cells to evade the immune system. We provided a brief overview of the MHC-I structure and its essential properties. Additionally, we have explored the function of MHC-I in PC treatment. Finally, we have reviewed emerging approaches to enhance anticancer vaccines and overcome MHC-I-mediated immune evasion in PC.

关键词： ACC   acetyl-CoA carboxylase   ACLY   ATP citrate lyase   ACSLs   long-chain acyl-coA synthetases   ACT   adoptive cell therapy   Akt   protein kinase B   AML   acute myeloid leukemia   ARF   ADP-ribosylation factor   ATGL   adipose triglyceride lipase   Ca2   calcium   CAR   chimeric antigen receptor   CMML   chronic myelomonocytic leukemia   CPT1A   carnitine palmitoyltransferase 1A   CTL   cytotoxic t lymphocytes   CYP1B1   cytochrome P450 1B1   DCs   dendritic cells   DHA   docosahexaenoic acid   EPA   eicosapentaenoic acid   FA   fatty acids   FABPs   fatty acid-binding proteins   FAO   fatty acid oxidation   FAS   de novo fatty acid synthesis   FASN   fatty acid synthase   FDA   food and drug administration   FTase   farnesyltransferase   GGTases I-III   geranylgeranyltransferases I, II, and III   GM-CSF BMDCs   granulocyte-macrophage colony-stimulating factor bone marrow-derived dendritic cells   GPR43   G-protein coupled receptor 43   HMG-CoA   3-hydroxy-3-methylglutaryl-coenzyme A   HNSCC   neck squamous cell carcinoma   ICB   immune checkpoint blockade   ICIs   immune checkpoint inhibitors   IFN   interferon   IFNAR1   IFN-γ receptor   ILC   innate lymphoid cell   LA   linoleic acid   LCFAs   long-chain fatty acids   LD   lipid droplet   LPS   lipopolysaccharide   MAGRIT   MAGE-A3-positive non-small cell lung cancer   MAVS   mitochondrial antiviral signaling protein   MEKi   MEK1/2 inhibition   MERCs   mitochondria-er contacts   Myr-CoA   myristoyl-coA   NDUFAF4   NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 4   NMT   N-myristoyltransferase   PAT   palmitoyl acyltransferase   PDAC   pancreatic ductal adenocarcinoma   PGC-1α   PPAR-γ coactivator 1α   PI3K   phosphoinositide 3-kinase   PPAR-γ   peroxisome proliferator-activated receptor γ   PKC   protein kinase C   PTM   posttranslational modification   RHOA   Ras homolog gene family, member a   ROS   reactive oxygen species   RIPK3   receptor interacting serine/threonine kinase 3   SCD1   stearoyl-CoA desaturase 1   SCAP   SERBP cleavage-activating protein   SCFAs   short-chain fatty acids   SHP1   Src homology region 2 domain-containing phosphatase-1   SREBP   sterol regulatory element-binding protein   STAT1   signal transducer and activator of transcription 1   STAT2   s  

摘要： Fatty acids (FA) are essential macromolecules in living organisms and play critical roles in processes such as cancer development, inflammation, and autoimmunity. Immune responses and metabolic changes are involved in tumor occurrence, development, invasion, and metastasis, and therapies targeting immunity and metabolism have gradually begun to be developed in clinical practice. Recent studies have revealed alterations in fatty acid metabolism in tumor microenvironment, suggesting that the modulation of fatty acid metabolism can affect the efficacy of immunotherapy. In this review, we summarize the effects of fatty acids on cancer immunotherapy in aspects including tumor cell metabolism, protein lipid modification, and clinical applications. A deeper understanding of the mechanisms by which FA and their metabolites participate in immune response can enhance our knowledge of their function in tumor development and their impact on the immune system, thereby providing new strategies for improving cancer immunotherapy.

关键词： Huaier   Colorectal cancer   TME   Immunotherapy   MHC I   AOM   Azoxymethane   DSS   Dextran sulfate sodium   CRC   Colorectal cancer   HR   Hazard ratio   CI   Confidence interval   IHC   Immunohistochemistry   IF   Immunofluorescence   LPS   Lipopolysaccharide   MFI   Mean fluorescence intensity   MHC I   Major histocompatibility complex class I   OS   Overall survival   PSM   Propensity score matching   PD-1   Programmed death 1   PD-L1   Programmed Death-Ligand 1   TME   Tumor microenvironment   TEM   Transmission electron microscopy  

摘要： Background Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, primarily due to its immunosuppressive microenvironment that facilitates immune evasion and resistance to therapy. Although the traditional Chinese medicine Trametes robiniophila Murr (Huaier) has been shown to exert anti-tumor effects, its immunomodulatory potential in CRC and mechanistic interaction with immune checkpoints have not been investigated. Results Treatment with Huaier significantly improved overall survival in CRC patients (HR=0.682, 95 % CI=0.576–0.809) and reduced tumor burden in both AOM/DSS-induced colitis-associated cancer and subcutaneous models. Notably, Huaier restored intestinal barrier integrity and reprogramed the tumor immune landscape by upregulating the expression of major histocompatibility complex class I (MHC I), which enhanced CD8+ T cell infiltration and cytolytic activity while depleting regulatory T cells. Mechanistically, Huaier activated the STAT1-MHC I pathway, leading to the upregulation of MHC I antigen presentation components, which facilitates the effective recognition of neoantigens by cytotoxic T cells. Crucially, in patient-derived organoids, Huaier synergized with anti-PD-1 therapy, enhancing T cell cytotoxicity. A subcutaneous tumor model was also developed to assess the synergistic effects of Huaier and anti-PD-1, demonstrating that combination therapy exhibited superior efficacy compared to monotherapy. Conclusions Our findings establish Huaier as a multifaceted immunoadjuvant that bridges innate and adaptive immunity in CRC. This natural agent offers a translatable strategy to enhance the therapeutic efficacy of existing immunotherapies of CRC patients.

关键词： Simvastatin   Skeletal muscle   Dose-finding study   Pharmacokinetics   Exercise   Atrophy   Akt   protein kinase B   ARRIVE   Animal Research: Reporting of In Vivo Experiments   AUC   area under the curve   CE   collision energy   C   max   maximal concentration   CS   citrate synthase   CTRL   control   CXP   collision cell exit potential   DP   declustering potential   EDL   extensor digitorum longus   EDTA   ethylenediaminetetraacetic acid   GCLC   glutamate-cysteine ligase catalytic subunit   GSH   reduced glutathione   GSSG   oxidized glutathione   HDL-C   high-density lipoprotein cholesterol   Hk2   nuclear hexokinase 2   HMG-CoA   β-hydroxy β-methylglutaryl-CoA   LC-MS/MS   liquid chromatography-mass spectrometry/mass spectrometry   LDL-C   low-density lipoprotein cholesterol   LLOQ   lower limit of quantification   MHC   myosin heavy chain   mtDNA   mitochondrial DNA   mTOR   mammalian target of rapamycin   MuRF-1   muscle RING-finger protein-1   ND1   NADH dehydrogenase subunit 1   NEM   N-ethylmaleimide   NQO1   NAD(P)H quinone dehydrogenase 1   NRF2   nuclear factor erythroid-2-related factor 2   PGC-1α   peroxisome proliferator-activated receptor γ coactivator 1α   PK   pharmacokinetics   rpS6   ribosomal protein S6   SAMS   statin-associated muscle symptoms   SOD   superoxide dismutase   VLDL-C   very low-density lipoprotein cholesterol  

摘要： Statins are highly effective in reducing plasma LDL-cholesterol but may be myotoxic. Since the relationship between statin exposure and myotoxicity is not clearly established, the current study aimed to compare blood and skeletal muscle concentrations with myotoxicity in male mice treated orally with 5, 10 and 25 mg/kg/day simvastatin for 3 weeks. After the first dose, simvastatin blood pharmacokinetics was dose-dependent, with exposures corresponding to humans treated with 80, 160 and 400 mg/day simvastatin. Skeletal muscle concentrations 24 h after the last dose of the three weeks-treatment period were dose-dependent with concentrations in the low nanomolar range. Simvastatin inhibited activation of key components of the insulin signaling pathway starting at 5 mg/kg/day whereas effects on physical performance and muscle strength were more accentuated at 10 than at 5 or 25 mg/kg/day. Simvastatin 25 mg/kg/day increased the SOD2 muscle protein expression. Simvastatin decreased gastrocnemius muscle total and reduced glutathione. In conclusion, oral administration of simvastatin from 5 to 25 mg/kg/day to mice showed linear pharmacokinetics and achieved blood concentrations equivalent to those obtained in humans treated with therapeutic to supratherapeutic doses. At 25 mg/kg simvastatin, myotoxicity is less accentuated than at 10 mg/kg, possibly due to induction of protective mechanisms.

关键词： ME/CFS   KIR   HLA   Association  

摘要： Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease with unknown cause. Involvement of infection and immune dysregulation has been suggested, including changes in immune cell subsets and abnormal functions of natural killer (NK) cells. The regulatory NK cell receptors, killer cell immunoglobulin-like receptors (KIR) have previously been investigated in small cohorts of ME/CFS patients with conflicting results regarding gene content. Here, we studied KIR genes also at the allelic level using high-resolution sequencing, in 418 ME/CFS patients and 473 healthy controls. Human leukocyte antigen (HLA) class I genotype data were included for KIR ligand annotation. Our healthy control data represent KIR frequencies for a Norwegian population, which have not previously been reported. We found no association between ME/CFS and KIR gene content or copy number variations. However, our data suggested that specific KIR alleles at loci encoding inhibitory receptors were associated with ME/CFS, which was further supported by allelic haplotype analyses. Three alleles were more frequent in patients, i.e. KIR3DL3*002 (OR = 1.43, 95 % CI (1.09–1.86), p = 0.009), KIR3DL1*020 (OR = 2.20, 95 % CI (1.19–4.06), p = 0.01) and KIR3DL2*009 (OR = 1.56, 95 % CI (1.09–2.23), p = 0.01), while two alleles had a reduced patient frequency, i.e. KIR3DL3*013 (OR = 0.60, 95 % CI (0.42–0.86), p = 0.005) and KIR3DL2* 010 (OR = 0.46, 95 % CI (0.30–0.71), p = 0.0005). Our data support an involvement of NK cells in ME/CFS.

关键词： AMR   Antibody-mediated rejection (pAMR, Pathologic AMR)   ATG   Antithymocyte globulin   HLA   Human leukocyte antigens   IVIG   Intravenous immunoglobulins   MFI   Mean fluorescence intensity   OHT   Orthotopic heart transplant   TPE   Therapeutic plasma exchange   allosensitization   daratumumab   desensitization   pediatric heart transplant   complex congenital heart disease  

摘要： Allosensitization remains a significant obstacle for highly sensitized pediatric heart transplant candidates and recipients, particularly in the era of complex congenital heart disease palliations. Current desensitization strategies are limited, have variable efficacy, and lack durable response. Daratumumab, a monoclonal antibody targeting CD38 which is highly present on plasma cells and natural killer cells, is a novel and emerging option that has been successfully used for desensitization before heart transplantation in adults and to treat antibody-mediated rejection in solid organ recipients. However, there are limited data of its use in the pediatric population. We present our institution’s complete experience with daratumumab in 4 highly sensitized patients with reasonable tolerability and encouraging response.