课程文献中心 更多>>

关键词： 1,25D   1,25-dihydroxyvitamin D   1   a   D   1   a   -hydroxyvitamin D (alfacalcidol)   25D   25-hydroxyvitamin D   AIRE   autoimmune regulator   AMP   antimicrobial peptide   APC   antigen-presenting cell   ARI   acute respiratory tract infection   ASL   airway surface liquid   CAMP/LL3   7 cathelicidin antimicrobial peptide   CD   Crohn’s disease   CKD   chronic kidney disease   DBP   vitamin D binding protein   DC   dendritic cell   EAE   experimental autoimmune encephalomyelitis   EB1089   eocalcitol   E.coli   Escherichia coli   HBD2   human   β   -defensin 2   HDACi   histone deacetylase inhibitor   IBD   inflammatory bowel disease   ICI   immune checkpoint inhibitor   IFN   g   interferon-gamma   Ig   immunoglobulin   IIH   infantile idiopathic hypercalcemia   IL   interleukin   iNKT   invariant natural killer T cell   irAE   immune-related adverse effect   KO   knockout   LIC   innate lymphoid cell   LPS   lipopolysaccharide   LXR   liver X receptor   MHC   major histocompatibility complex   MS   multiple sclerosis   mTEC   medullary thymic epithelial cell   NF   κ   B   nuclear factor kappa B   NK   natural killer cell   NOD   nonobese diabetic   OCT   22-oxacalcitriol (maxacalcito)   PBMC   peripheral blood mononuclear cell   PD-1   programmed-death protein 1   PPAR   peroxisomal proliferator-activated receptor   PTH   parathyroid hormone   PRR   pattern recognition receptor   RAG   recombinase activating gene   RAR   retinoic acid receptor   RCT   randomized, double-blind, placebo-controlled trial   RXR   retinoid X receptor   T1D   type 1 diabetes   TB   tuberculosis   TCR   T cell receptor   TEC   thymic epithelial cell   TGF   b   transforming growth factor beta   Tfh   follicular helper T cell   TLR   toll-like receptor   TR   thyroid hormone receptor   Treg   regulatory T cell   UTI   urinary tract infections   UVB   ultraviolet B   VDR   vitamin D receptor   VDRE   vitamin D response element   WT   wild-type  

摘要： Vitamin D was discovered as the cure for nutritional rickets, a disease of bone growth arising from inadequate intestinal calcium absorption, and for much of the 20th century, it was studied for its critical role in calcium homeostasis. However, we now recognize that the vitamin D receptor and vitamin D metabolic enzymes are expressed in numerous tissues unrelated to calcium homeostasis. Notably, vitamin D signaling can induce cellular differentiation and cell cycle arrest. Moreover, the vitamin D receptor and the enzyme CYP27B1, which produces the hormonal form of vitamin D, 1,25dihydroxyvitamin D (1,25D), are expressed throughout the immune system. In addition, CYP27B1 expression in immune cells is regulated by physiological inputs independent of those controlling its expression in calcium homeostatic tissues. These observations have driven the development of 1,25D- like secosteroidal analogs and nonsecosteroidal analogs to separate the effects of vitamin D on cell differentiation and function from its calcemic activities. Notably, some of these analogs have had considerable success in the clinic in the treatment of inflammatory and immune-related disorders. In this review, we described in detail the mechanisms of vitamin D signaling and the physiological signals controlling 1,25D synthesis and catabolism, with a focus on the immune system. We also surveyed the effects of 1,25D and its analogs on the regulation of immune system function and their implications for human immune-related disorders. Finally, we described the potential of vitamin D analogs as anticancer therapeutics, in particular, their use as adjuncts to cancer immunotherapy. Significance Statement: Vitamin D signaling is active in both the innate and adaptive arms of the immune system. Numerous vitamin D analogs, developed primarily to minimize the dose-limiting hypercalcemia of the active form of vitamin D, have been used widely in preclinical and clinical studies of immune system regulation. This r

关键词： IL23R   IL-23-signalling   Ancient genomics   Crohn's disease   Ulcerative colitis   Inflammatory bowel diseases  

摘要： Background The hypomorphic variant rs11209026-A in the IL23R gene provides significant protection against immune-related diseases in Europeans, notably inflammatory bowel diseases (IBD). Today, the A-allele occurs with an average frequency of 5% in Europe. Methods This study comprised 251 ancient genomes from Europe spanning over 14,000 years. In these samples, the investigation focused on admixture-informed analyses and selection scans of rs11209026-A and its haplotypes. Findings rs11209026-A was found at high frequencies in Anatolian Farmers (AF, 18%). AF later introduced the allele into the ancient European gene-pool. Subsequent admixture caused its frequency to decrease and formed the current southwest-to-northeast allele frequency cline in Europe. The geographic distribution of rs11209026-A may influence the gradient in IBD incidence rates that are highest in northern and eastern Europe. Interpretation Given the dramatic changes from hunting and gathering to agriculture during the Neolithic, AF might have been exposed to selective pressures from a pro-inflammatory lifestyle and diet. Therefore, the protective A-allele may have increased survival by reducing intestinal inflammation and microbiome dysbiosis. The adaptively evolved function of the variant likely contributes to the high efficacy and low side-effects of modern IL-23 neutralisation therapies for chronic inflammatory diseases. Copyright (c) 2025 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://***/licenses/by/4.0/).

关键词： HLA-C*03:689   novel allele   sequence-based typing  

摘要： The novel HLA-C*03:689 allele differs from HLA-C*03:03:01:01 by two nucleotide substitutions in codons 81 and 82 in exon 2.

关键词： Lysophosphatidic acid   Porcine skin-derived stem cells   Tumor necrosis factor alpha   Cryopreservation   Apoptosis  

摘要： Preserving the viability and functionality of stem cells during cryopreservation is crucial for their successful application in regenerative medicine. The aim of this study is to investigate the effect of lysophosphatidic acid (LPA) on reducing the apoptosis of cryopreserved porcine skin-derived stem cells (pSDSCs). Our findings revealed that LPA, at a concentration of 5 mu M, significantly improved viability and reduced apoptosis in cryopreserved pSDSCs. Furthermore, our data indicated that LPA enters pSDSCs through receptor type 1 (LPAR1). In cryopreserved pSDSCs, after LPA treatment, the expression level of tumor necrosis factor alpha (TNF-alpha) protein decreased, suggesting TNF-alpha involvement in the regulation of the anti-apoptotic process. Additionally, we found that resiquimod (R848), a TNF-alpha activator, increased the level of apoptosis in cryopreserved pSDSCs. When cryopreserved pSDSCs were treated with both LPA and R848, the protective effect of LPA against apoptosis was decreased. In conclusion, our study demonstrates that LPA could effectively counteract the effect of TNF alpha-induced apoptosis, thereby enhancing the survival rates of cryopreserved pSDSCs. Importantly, this study explored a novel mechanism of reducing apoptosis in cryopreserved stem cells.

关键词： HLA   HLA-C   new allele   sequencing-based typing  

摘要： The new allele HLA-C*07:1130N differs from HLA-C*07:02:01:01 by one nonsense nucleotide substitution in exon 3.

关键词： cloning   HLA-A*02:07:08   long-range PCR   novel allele   Sanger sequencing  

摘要： The full genomic sequence shows HLA-A*02:07:08 differs from HLA-A*02:07:01:01 only at position 131 in exon 3.

关键词： AI   artificial intelligence   ALK   TGF-   β   receptor kinase   AKT   protein kinase b   AMPK   5’ monophosphate-activated protein kinase   Ang-II   angiotensin II   ANGPT   angiopoietin   BCL2   B-cell lymphoma 2   BP   blood pressure   CAF   cancer-associated fibroblast   CANTOS   Canakinumab Anti-Inflammatory Thrombosis Outcome Study   CAR-T   chimeric antigen receptor T cell   CCL   C-C Motif Chemokine ligand   CDK   cyclin-dependent kinases   CHIP   clonal hematopoiesis of indeterminate potential   CREB   cAMP response element   CRP   C reactive protein   CVD   cardiovascular disease   CYP   cytochrome P450   D2-HG   D-2-hydroxyglutarate   DAMPs   damage-associated molecular patterns   DI   drug interaction   DLL   δ   -like ligand   DNMT3A   DNA methyltransferase 3A   EC   endothelial cell   ECM   extracellular matrix   EGF   epithelial growth factor   ELK-1   ETS-like 1 protein   ER   estrogen receptor   ERK1/2   extracellular signal-regulated kinase ½   ETS   erythroblast transformation specific   US FDA   United States Food and Drug Administration   GPCR   chemokine G protein-coupled receptor   GWAS   genome-wide association studies   HER2   human epidermal growth factor 2   HGF   hepatocyte growth factor   HF   heart failure   HIF-1   hypoxia-inducible factor 1   HSPC   hematopoietic stem progenitor cells   HUVEC   human umbilical cord endothelial cell   ICI   immune checkpoint inhibitor   IDH   isocitrate dehydrogenase   IFN-   γ   interferon   γ   IL   interleukin   KLF   rüppel-like factor   LPS   lipopolysaccharides   LV   left ventricular   MAPK   mitogen-activated protein kinase   MAX   Myc-associated factor X   MHC   major histocompatibility complex   MDSC   myeloid-derived suppressor cell   MEK   MAPK kinase   MEKI   MAPK kinase inhibitor   MI   myocardial infarction   MMPs   matrix metalloproteinases   MYC   Myc proto-oncogene protein   NF-κB   nuclear factor kappa-light-chain-enhancer of activated B cells   NK   natural killer   NLRP3   NOD-like receptor protein 3   NOTCH   Neurogenic locus notch homolog protein   PAMP   pathogen-associated molecular patterns   PD   pharmacodynamics   PDGF   platelet-derived growth factor   PD-L1   programmed death-ligand 1   PFKFB3   6-phosphofructokinase/2,6-bisphosphatase 3   PI3K   phosphatidylinositol 3-kinase   PK   ph  

摘要： Cancer and cardiovascular disease (CVD) are the 2 biggest killers worldwide. Specific treatments have been developed for the 2 diseases. However, mutual therapeutic targets should be considered because of the overlap of cellular and molecular mechanisms. Cancer research has grown at a fast pace, leading to an increasing number of new mechanistic treatments. Some of these drugs could prove useful for treating CVD, which realizes the concept of cancer drug repurposing. This review provides a comprehensive outline of the shared hallmarks of cancer and CVD, primarily ischemic heart disease and heart failure. We focus on chronic inflammation, altered immune response, stromal and vascular cell activation, and underlying signaling pathways causing pathological tissue remodeling. There is an obvious scope for targeting those shared mechanisms, thereby achieving reciprocal preventive and therapeutic benefits. Major attention is devoted to illustrating the logic, advantages, challenges, and viable examples of drug repurposing and discussing the potential influence of sex, gender, age, and ethnicity in realizing this approach. Artificial intelligence will help to refine the personalized application of drug repurposing for patients with CVD. Significance Statement: Cancer and cardiovascular disease (CVD), the 2 biggest killers worldwide, share several underlying cellular and molecular mechanisms. So far, specific therapies have been developed to tackle the 2 diseases. However, the development of new cardiovascular drugs has been slow compared with cancer drugs. Understanding the intersection between pathological mechanisms of the 2 diseases provides the basis for repurposing cancer therapeutics for CVD treatment. This approach could allow the rapid development of new drugs for patients with CVDs. (c) 2024 The Authors. Published by Elsevier Inc. on behalf of American Society for Pharmacology and Experimental Therapeutics. This is an open access article under the CC BY-NC license

关键词： Seneca Valley virus   LncRNA   IFN-alpha  

摘要： lncRNAs play important regulatory roles in almost every aspect of physiological processes. However, the mechanisms by which animal-encoded lncRNAs regulate the interaction of viral infection with host antiviral immunity are unknown. To explore the mechanisms of lncRNA regulation of SVV infection and interferon responses. We performed complete transcriptome sequencing analysis of porcine kidney 15 (PK-15) after infection with SVV-1 strain and IFN-alpha treatment, and identified and screened the sequencing data to obtain potential functional lncRNA-ISL. selected genes were knocked down using CRISPR/Cas9 guide RNAs (gRNAs), and the results of the sequencing were monitored by qRT-PCR and protein blotting in multiple cell lines for selected gene mRNAs and their proteins as well as SVV infection. The results showed that 68 lncRNAs were significantly altered by IFN-alpha and 176 lncRNAs were significantly altered after SVV infection. We found that lncRNA-ISL gRNA significantly inhibited SVV infection compared to negative gRNA control. The expression of the antiviral ISG G1P3 was significantly increased following lncRNA-ISL gRNA editing compared to negative gRNA control in SVV-infected PK-15 cells. We observed that lncRNA-ISL regulation of SVV was independent of JAK-STAT signaling and not associated with G1P3 DNA methylation. Finally, we confirmed that the regulatory effect of lncRNA-ISL on G1P3 occurs during the initial transcription.

关键词： virus microenvironment   viral infection   intercellular communication   cell-to-cell communication   extracellular vesicles   secreted proteins   secretome   secreted metabolites   cell surface   surfaceome   extracellular matrix   spatial profiling   multiplexed imaging   proteomics   microenvironment labeling   APC   antigen presenting cell   EBV   Epstein-Barr virus   ECM   extracellular matrix   EV   extracellular vesicle   HBV   hepatitis B virus   HCMV   human cytomegalovirus   HCV   hepatitis C virus   HPV   human papilloma virus   HSV   herpes simplex virus   IAV   influenza A virus   IF   immunofluorescence   IFN   interferon   IMS   imaging MS   LCM   laser capture microdissection   LMP   latent membrane protein   MALDI   matrix-assisted laser desorption/ionization   MHC   major histocompatibility complex   MS   mass spectrometry   NK   natural killer   PPI   protein–protein interaction   sCP-mCh   secreted and cell penetrable mCherry   SIV   simian immunodeficiency virus   VME   virus microenvironment   ZIKV   Zika virus  

摘要： Intercellular communication is fundamental to multicellular life and a core determinant of outcomes during viral infection, where the common goals of virus and host for persistence and replication are generally at odds. Hosts rely on encoded innate and adaptive immune responses to detect and clear viral pathogens, while viruses can exploit or disrupt these pathways and other intercellular communication processes to enhance their spread and promote pathogenesis. While virus-induced signaling can result in systemic changes to the host, striking alterations are observed within the cellular microenvironment directly surrounding a site of infection, termed the virus microenvironment (VME). Mechanisms employed by viruses to condition their VMEs are emerging and are critical for understanding the biology and pathologies of viral infections. Recent advances in experimental approaches, including proteomic methods, have enabled study of the VME in unprecedented detail. In this review article, we provide a primer on proteomic approaches used to study how viral infections alter intercellular communication, highlighting the ways in which these approaches have been implemented and the exciting biology they have uncovered. First, we consider the different molecules secreted by an infected cell, including proteins, either soluble or contained within extracellular vesicles, and metabolites. We further discuss the modalities of interactions facilitated by alteration at the cell surface of infected cells, including immunopeptide presentation and interactions with the extracellular matrix. Finally, we review spatial profiling approaches that have allowed distinguishing how specific subpopulations of cells within a VME respond to infection and alter their protein composition, discussing valuable insights these methods have offered.