Metabolic brain disease最新文献

{"title":"The potential of alphapinene as a therapeutic agent for maternal hypoxia-induced cognitive impairments: a study on HO-1 and Nrf2 gene expression in rats.","authors":"Mahsa Mahmoodi Atabaki, Zohreh Ghotbeddin, Kaveh Rahimi, Mohammad Reza Tabandeh","doi":"10.1007/s11011-024-01519-0","DOIUrl":"https://doi.org/10.1007/s11011-024-01519-0","url":null,"abstract":"<p><p>This research seeks to address the gap in past studies by examining the role of the Nrf2 (nuclear factor erythroid 2-related factor 2) and HO-1 (heme oxygenase-1) signaling pathways in hypoxia and the potential effects of alpha-pinene on these factors. Wistar rats were divided into 7 experimental groups (n = 7): 1) control, 2 and 3) groups receiving alpha-pinene 5 and 10 mg/kg (i.p., for 21 days), 4) hypoxia group (7% O2 and 93 N2, 3 h, GD14 to GD18), 5 and 6) groups receiving alpha-pinene 5 and 10 after hypoxia. Memory and cognition were evaluated using the Morris water maze and novel object recognition tests. Inflammation was assessed by ELISA method and Nrf2 and HO-1 Nrf2 gene expression was evaluated using real-time PCR in the hippocampus. Recognition index, spatial memory, and Nrf2-H0-1 gene expression significantly reduced in the hypoxia group compared to the control group, and alpha-pinene injection in the offspring improved cognition, memory, and Nrf2- HO-1 gene expression in the groups were affected by hypoxia. Inflammation factors in the hypoxia group were higher than the control, but alpha-pinene significantly decreased inflammation ( all cases p < 0.05). Based on the results, it seems that alpha-pinene prevents cognitive and memory loss by increasing Nrf2 and H0-1 gene expression and reducing inflammation.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"112"},"PeriodicalIF":3.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute lipid droplet accumulation induced by the inhibition of the phospholipase DDHD2 does not affect the level, solubility, or phosphoserine-129 status of α-synuclein.","authors":"Magdalena M Bolsinger, Tim E Moors, Lisa Brontesi, Silke Nuber, Ulf Dettmer, Nagendran Ramalingam","doi":"10.1007/s11011-025-01534-9","DOIUrl":"https://doi.org/10.1007/s11011-025-01534-9","url":null,"abstract":"<p><p>α-Synuclein (αS) is a 140 amino-acid neuronal protein highly enriched in presynaptic nerve terminals. Its progressive accumulation in Lewy bodies and neurites is the hallmark of Parkinson's disease (PD). A growing number of studies highlights a critical interplay between lipid metabolism and αS biology. Some of these works postulate a physical interaction between αS and lipid droplets (LDs), but further clarity is needed, not least because typically exogenous αS and/or heterologous systems have been studied. Here, we investigated the effects of acute LD accumulation on endogenous wild-type αS in primary rat cortical neurons. To induce robust LD accumulation within hours, we inhibited the neuronal triacylglycerol hydrolase DDHD2, a phospholipase, using the compound KLH45. KLH45-induced LD accumulation did not affect total levels, phosphoserine-129 status, or solubility of αS, and no co-localization between LDs and αS was observed under these conditions. These findings suggest that a \"second hit\" and/or a specific LD lipid composition may be necessary for lipid excess to affect αS homeostasis. Our work thus contributes to the debate on αS structure and lipid interaction.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"111"},"PeriodicalIF":3.2,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attenuating hyperammonemia preserves protein synthesis and muscle mass via restoration of perturbed metabolic pathways in bile duct-ligated rats.","authors":"Cristina R Bosoi, Avinash Kumar, Mariana M Oliveira, Nicole Welch, Marc-André Clément, Mélanie Tremblay, Gabriella A M Ten-Have, Marielle P K J Engelen, Chantal Bémeur, Nicolaas E P Deutz, Srinivasan Dasarathy, Christopher F Rose","doi":"10.1007/s11011-024-01525-2","DOIUrl":"https://doi.org/10.1007/s11011-024-01525-2","url":null,"abstract":"<p><p>Sarcopenia and hepatic encephalopathy (HE) are complications of chronic liver disease (CLD), which negatively impact clinical outcomes. Hyperammonemia is considered to be the central component in the pathogenesis of HE, however ammonia's toxic effects have also been shown to impinge on extracerebral organs including the muscle. Our aim was to investigate the effect of attenuating hyperammonemia with ornithine phenylacetate (OP) on muscle mass loss and associated molecular mechanisms in rats with CLD. Six-week bile duct-ligated (BDL) rats and Sham-operated controls were treated with OP (1 g/kg, oral) for 5 weeks. Body composition, assessed by EchoMRI, and muscle protein fractional synthesis rate were evaluated. Signalling mechanisms regulating protein homeostasis, ATP content and metabolic intermediates in the tricarboxylic acid cycle (TCA) in skeletal muscle were quantified. OP treatment attenuated hyperammonemia, prevented brain edema and improved locomotor activity in BDL rats. Increased muscle ammonia, reduction in lean body mass, decreased muscle protein synthesis rate and ATP content were restored in OP-treated versus saline-treated BDL rats. TCA cycle intermediary metabolite, α-ketoglutarate, alterations of molecular markers regulating protein homeostasis including mTOR signalling and autophagy, were also preserved in muscle of OP-treated BDL rats. OP attenuated hyperammonemia, preserved muscle protein synthesis and prevented muscle mass loss in a preclinical model of CLD through restoration of perturbed signalling responses and altered TCA intermediary metabolites. Ammonia-lowering strategies have the potential for rapid clinical translation for simultaneous neuroprotection and sarcopenia prevention in patients with CLD.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"110"},"PeriodicalIF":3.2,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the molecular characterization of PANoptosis-related genes with features of immune dysregulation in Alzheimer's disease based on bulk and single-nuclei RNA sequencing.","authors":"Hanjie Liu, Maochun You, Hui Yang, Xiao Wu, Siyu Zhang, Sihan Huang, Huijuan Gao, Lushuang Xie","doi":"10.1007/s11011-025-01540-x","DOIUrl":"https://doi.org/10.1007/s11011-025-01540-x","url":null,"abstract":"<p><p>The immune system has emerged as a major factor in the pathogenesis of Alzheimer's disease (AD). PANoptosis is a newly defined programmed cell death mechanism related to many inflammatory diseases. This study aimed to identify the differentially expressed (DE) PANoptosis-related genes with characteristics of immune dysregulation (PRGIDs) in AD using bioinformatics analysis of bulk RNA-seq and single-nuclei RNA sequencing (snRNA-seq) data. To improve the robustness of gene selection, we integrated 3 microarray and 6 snRNA-seq datasets from the Gene Expression Omnibus (GEO), which allowed us to not only examine overall gene expression patterns but also assess the cellular specificity of gene expression at the single-cell level. This approach helped to identify cell-type-specific gene alterations that may be masked in bulk RNA-seq analyses. Relevant PANoptosis, immune dysregulation, and AD-related genes were obtained from the Genecards database. The AlzData database was also used in this study. Expression validation, the least absolute shrinkage and selection operator (LASSO) regression model, and CytoHubba algorithms were applied for key DE-PRGIDs selection. LASSO, Logistic, and Cox regressions were used to construct prognostic models. The receiver operating characteristic (ROC) curve and correlation analyses were conducted on key DE-PRGIDs. The Seurat package in R software was employed for performing snRNA-seq data processing. Uniform manifold approximation and projection (UMAP) was utilized for cell type annotation and PRGID cell visualization. The violin plot was applied for displaying expression levels of PRGIDs. High-dimensional consensus weighted gene co-expression network analysis (hdWGCNA) was conducted on microglia to identify gene modules and hub genes. Venn diagram analysis identified 250 PRGIDs and 39 DE-PRGIDs. NFKBIA was identified as the key gene. Prognostic models based on the expression level of NFKBIA were obtained. ROC curve analysis revealed its area under the curve (AUC) value: 0.661 in training set and 0.836 in validation set. The heatmap displayed the result of correlation analysis. SnRNA-seq data analysis identified 7 cell types. The UMAP and violin plots revealed highly expressed PRGIDs in microglia with remarkable differences between healthy controls and AD. hdWGCNA identified PVT1 and APOE as hub genes associated with microglia. In conclusion, our findings provide evidence that PANoptosis may play a role in the immune dysregulation observed in AD. PVT1 has been implicated in AD pathogenesis, potentially exerting its effects through the miR-488-3p/FOXD3/SCN2A axis.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"109"},"PeriodicalIF":3.2,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L-carnitine protects against oxidative damage and neuroinflammation in cerebral cortex of rats submitted to chronic chemically-induced model of hyperphenylalaninemia.","authors":"Jéssica Lamberty Faverzani, Gilian Guerreiro, Franciele Fatima Lopes, Angela Sitta, Daniella de Moura Coelho, Caroline Paula Mescka, Luísa Degrandi Sehn, Gabriel de Lima Rosa, Amanda Muliterno Domingues Lourenço de Lima, Esteban Alberto Gonzalez, Rafael Teixeira Ribeiro, Rafael Palavro, Adriana Simon Coitinho, Guilherme Baldo, Moacir Wajner, Carmen Regla Vargas","doi":"10.1007/s11011-025-01537-6","DOIUrl":"https://doi.org/10.1007/s11011-025-01537-6","url":null,"abstract":"<p><p>Phenylketonuria is a genetic disorder characterized by high phenylalanine levels, the main toxic metabolite of the disease. Hyperphenylalaninemia can cause neurological impairment. In order to avoid this symptomatology, patients typically follow a phenylalanine-free diet supplemented with a synthetic formula that provides essential amino acids, including L-carnitine. This work aims to evaluate the potential neuroprotective effects of L-carnitine treatment in the cerebral cortex of rats submitted to a chronic chemically-induced model of Hyperphenylalaninemia, evaluating brain oxidative damage and neuroinflammation. We confirm the effectiveness of the animal model, through the increase of phenylalanine and L-carnitine in blood and cerebral cortex. L-carnitine treatment was effective in significantly decreasing the generation of reactive species and attenuating the superoxide dismutase (SOD) activity. Significant negative correlations between L-carnitine and superoxide dismutase as well as L-carnitine and reactive species generation were also found, reinforcing the involvement of oxidative stress and the effect of L-carnitine. Besides, L-carnitine attenuated the decrease in IL-4 levels, demonstrating both anti-inflammatory properties and a neuroprotective effect, through the decrease in the overexpression of the glial fibrillary acidic protein (GFAP) present in the cerebral cortex of rats with Hyperphenylalaninemia. Our results highlight the neuroprotective role of L-carnitine in the treatment of Phenylketonuria, mainly against neuroinflammation and the oxidative process, contributing to better clarify the pathophysiology of the disease.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"108"},"PeriodicalIF":3.2,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactulose use among patients with alcohol-related liver cirrhosis as a surrogate marker of hepatic encephalopathy: prevalence and association with mortality - a Danish nationwide cohort study.","authors":"Emma Celia Herting, Morten Daniel Jensen, Peter Jepsen","doi":"10.1007/s11011-025-01533-w","DOIUrl":"https://doi.org/10.1007/s11011-025-01533-w","url":null,"abstract":"<p><strong>Background & aims: </strong>Hepatic encephalopathy (HE), one of the most serious prognostic factors for mortality in alcohol-related cirrhosis (ALD cirrhosis), is not recorded in Danish healthcare registries. However, treatment of HE with lactulose, the universal first-line treatment, can be identified through data on filled prescriptions. This study aimed to investigate if lactulose can be used as a surrogate marker of HE.</p><p><strong>Methods: </strong>We used Danish healthcare registries to establish a cohort of patients with ALD cirrhosis diagnosed in 2000-2018. Lactulose users were identified using data on filled prescriptions. We computed the prevalence and cumulative incidence of lactulose use, and then matched lactulose users with cohort members who were not using lactulose. This matched dataset was used to identify predictors of lactulose initiation, and to examine the association between lactulose use and all-cause mortality.</p><p><strong>Results: </strong>We included 23,089 patients, among whom we identified 4,789 first-time lactulose users. The prevalence of lactulose usage rose to 11% within the first 6 months after ALD diagnosis and reached 19% 5 years after inclusion. The 1-year cumulative incidence of lactulose use was 31%, and predictors of initiating lactulose use were history of severe liver disease (ascites, portal hypertension, spontaneous bacterial peritonitis or gastrointestinal bleeding) or hepatocellular carcinoma. Lactulose use was associated with higher mortality (adjusted hazard ratio 1.61 [95% confidence interval 1.53; 1.69]).</p><p><strong>Conclusions: </strong>Lactulose is used by 10-20% of patients with ALD cirrhosis, primarily those with severe cirrhosis, and lactulose users have a markedly higher mortality than nonusers. We conclude that lactulose use can be used to estimate the prevalence of HE and to reduce confounding from HE, but it should not be used as a surrogate for HE in studies with HE as an outcome.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"107"},"PeriodicalIF":3.2,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the mechanism of Radix Bupleuri in the treatment of depression combined with SARS-CoV-2 infection through bioinformatics, network pharmacology, molecular docking, and molecular dynamic simulation.","authors":"Zexing Chen, Xinhua Wang, Wanyi Huang","doi":"10.1007/s11011-025-01536-7","DOIUrl":"https://doi.org/10.1007/s11011-025-01536-7","url":null,"abstract":"<p><strong>Background: </strong>Radix Bupleuri is commonly used in treating depression and acute respiratory diseases such as SARS-CoV-2 infection in China. However, its underlying mechanism in treating major depressive disorder combined with SARS-CoV-2 infection remains unclear.</p><p><strong>Aim: </strong>This study aims to elucidate the pharmacological mechanisms of Radix Bupleuri in treating major depressive disorder combined with SARS-CoV-2 infection, employing bioinformatics, network pharmacology, molecular docking, and dynamic simulation techniques.</p><p><strong>Method: </strong>Active ingredients and drug target genes of Radix Bupleuri were collected from TCMSP, PubChem, SwissTargetPrediction, and SuperPred databases. Differentially expressed genes were analyzed using datasets of SARS-CoV-2 infection and major depression disorder from the GEO database. The key genes were identified by using GO and KEGG functional analyses and STRING database. Machine learning methods were employed to predict core target gene, and ROC curve analysis validated the models' accuracy and the core gene expression had been analyzed and validated with other datasets. Molecular docking and dynamic simulation were conducted to verify the affinity of the active ingredients with core target gene. Finally, immune infiltration and correlation analyses between core target genes and immune cells were performed.</p><p><strong>Results: </strong>A total of 15 active ingredients, 1898 differentially expressed genes related to SARS-CoV-2 infection, and 814 differentially expressed genes related to major depression disorder were collected. 18 common genes were identified at the intersection of Radix Bupleuri, major depression disorder, and SARS-CoV-2 infection. The key gene JAK2 was identified through PPI network construction and machine learning model predictions. Molecular docking showed that the binding energies of the active ingredients with JAK2 were all below - 5 kcal/mol, with petunidin exhibiting the highest affinity. Molecular dynamic simulations further suggested stable interactions with JAK2. Immune infiltration analysis suggested that Radix Bupleuri in the context of depression combined with SARS-CoV-2 infection may promote the activation and generation of B cells, CD4 T cells, and CD8 T cells, while inhibiting the activation of mature dendritic cells, macrophages, natural killer cells, and neutrophils. Correlation analysis of JAK2 with immune cells indicated an association with macrophage activation and the inhibition of memory B cells and activated B cells.</p><p><strong>Conclusion: </strong>The active ingredients of Radix Bupleuri may exhibit both antidepressant and antiviral pharmacological effects in the progression of major depression disorder combined with SARS-CoV-2 infection, through a mechanism closely associated with the JAK2 target.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"105"},"PeriodicalIF":3.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating network pharmacology and experimental verification to reveal the ferroptosis-associated mechanism of Changpu-Yizhi-Wan in the treatment of Alzheimer's disease.","authors":"Rui Xiong, Hengxu Liu, Shipeng Zhang, Lu Wang, Lu Liu, Sicen Pan, Yu Zhang, Fengying Zhu, Yao Liu, Xiaodan Lai","doi":"10.1007/s11011-024-01504-7","DOIUrl":"https://doi.org/10.1007/s11011-024-01504-7","url":null,"abstract":"<p><p>To explore the pharmacological mechanism of Changpu-Yizhi-Wan (CYW) in the treatment of Alzheimer's disease (AD) from the perspective of ferroptosis based on network pharmacology and experimental verification. The Encyclopedia of Traditional Chinese Medicine 2.0 (ETCM2.0) database was used to collect the active components of CYW, and the putative targets were predicted in ETCM2.0 and SwissTargetPrediction database. The AD related targets were collected from GeneCards, comparative toxicogenomics database (CTD), Online Mendelian Inheritance in Man (OMIM), DisGeNET and Therapeutic Target Database (TTD), the ferroptosis related targets were collected from FerrDb V2 database, and the common targets of CYW, AD and ferroptosis were calculated by Venny2.1 platform. Protein-protein interaction (PPI) analysis was performed by STRING database, and the active compounds-target network and the PPI network were constructed using Cytoscape software. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathway enrichment analysis were performed through DAVID database. RSL3 was used to induce HT22 cells to establish a neuronal ferroptosis cell model, and the inhibitory effect of CYW on neuronal ferroptosis was evaluated by cell viability assay, intracellular iron assay and lipid peroxidation staining. The ferroptosis-associated key protein expressions of Nrf2, SLC7A11, GPX4 and FTH1 were detected by Western blot. A total of 100 candidate compounds were identified from CYW, and 1129 putative targets were obtained. 3924 AD-related targets and 564 ferroptosis-related targets were collected, respectively. There were 78 common targets between them and CYW targets, which were potential targets for CYW to regulate ferroptosis in the treatment of AD. PPI network analysis identified 10 key targets, including TP53, IL6, STAT3, HIF1A, NFE2L2, and others. GO, KEGG and Reactome enrichment analysis showed that 78 potential targets were involved in the regulation of ferroptosis and Nrf2-mediated gene transcription. Molecular docking showed that some active components of CYW had good affinity with Nrf2. In RSL3-induced HT22 cells, CYW significantly improved cell viability, reduced intracellular iron levels and inhibited lipid peroxidation, and improved the protein expression of Nrf2, SLC7A11, GPX4 and FTH1. The pharmacological mechanism of CYW in the treatment of AD may be related to the regulation of Nrf2/SLC7A11/GPX4/FTH1 axis to inhibit neuronal ferroptosis.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"106"},"PeriodicalIF":3.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatic encephalopathy in non-cirrhotic portal hypertension.","authors":"Babu Lal Meena, Ananthu Narayan S J, Shiv Kumar Sarin","doi":"10.1007/s11011-024-01522-5","DOIUrl":"https://doi.org/10.1007/s11011-024-01522-5","url":null,"abstract":"<p><p>Hepatic encephalopathy (HE) is traditionally associated with hepatic parenchymal diseases, such as acute liver failure and cirrhosis. Its prevalence in non-cirrhotic portal hypertension (NCPH) patients, extrahepatic portal vein obstruction (EHPVO), and non-cirrhotic portal fibrosis (NCPF) is less well described. HE in NCPH allows one to study the effect of portosystemic shunting and ammonia without significant hepatic parenchymal injury. The current review narrates the spectrum and management of hepatic encephalopathy in NCPH patients. We synthesized data from various studies on the occurrence and management of HE in NCPH, mainly EHPVO, idiopathic non-cirrhotic portal hypertension (INCPH), and porto-sinusoidal vascular disease (PSVD). The prevalence of minimal hepatic encephalopathy (MHE) in NCPH is reported from 12 to 60%, depending on the condition and diagnostic criteria. MHE was reported in nearly a third of EHPVO patients. Studies show that venous ammonia levels are significantly elevated in patients with MHE and spontaneous shunts (82.4 ± 20.3 vs. 47.1 ± 16.7 µmol/L, P = 0.001). Large portosystemic shunts substantially increase the risk of HE, with 46-71% of patients with persistent or recurrent HE having identifiable shunts. Management of HE in NCPH primarily focuses on reducing ammonia levels through lactulose, which has shown improvement in 53% of patients with MHE after three months (P = 0.001). Shunt occlusion in patients with large portosystemic shunts is helpful in selected cases. HE in NCPH, particularly in EHPVO, is associated with elevated ammonia levels and spontaneous shunts. Despite the high prevalence of HE in NCPH, this is still a neglected aspect in the care of NCPH. A high index of suspicion and the application of appropriate screening tools are crucial for timely diagnosis and management. HE screening tools that are well-studied in cirrhosis, are also valid in NCPH. Effective management strategies include lactulose, rifaximin, dietary modifications, and shunt embolisation in some cases. Future research should focus on the long-term natural history and efficacy of treatment strategies in this population.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"103"},"PeriodicalIF":3.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging role of adaptive immunity in diabetes-induced cognitive impairment: from the periphery to the brain.","authors":"Genhui Yang, Runtao Su, Jie Bu, Ying Li, Xueling Lin, Jiahui Jin, Yanjun Zhang, Pengwei Zhuang, Hong Guo, Qingsheng Yin","doi":"10.1007/s11011-025-01532-x","DOIUrl":"https://doi.org/10.1007/s11011-025-01532-x","url":null,"abstract":"<p><p>Diabetic cognitive impairment (DCI) is a central nervous system complication induced by peripheral metabolic dysfunction of diabetes mellitus. Cumulative studies have shown that neuro-immune crosstalk is involved in the pathological progression of DCI. However, current studies mostly focus on the interaction between innate immunity cells and neurons, while ignoring the role of adaptive immunity cells in DCI. Notably, recent studies have revealed adaptive immune cells are involved in cognitive development and the progression of neurodegenerative diseases. Equally important, accumulated past studies have also shown that diabetic patients experience imbalanced peripheral adaptive immune homeostasis and disrupted transmission of adaptive immune cells to the central system. Therefore, this review first updated the cognitive mechanism of adaptive immune regulation, and then summarized the contribution of adaptive immunity to DCI from the aspects of peripheral adaptive immune homeostasis, transmission pathways, and brain tissue infiltration. Furthermore, we also summarized the potential of anti-diabetic drugs to regulate adaptive immunity, and looked forward to the potential value of regulatory adaptive immunity in the prevention and treatment of DCI, to provide a new strategy for the prevention and treatment of DCI.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 1","pages":"102"},"PeriodicalIF":3.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}