Molecular Medicine最新文献

{"title":"Progesterone (P4) ameliorates cigarette smoke-induced chronic obstructive pulmonary disease (COPD).","authors":"Bin Xie, Qiong Chen, Ziyu Dai, Chen Jiang, Xi Chen","doi":"10.1186/s10020-024-00883-y","DOIUrl":"10.1186/s10020-024-00883-y","url":null,"abstract":"<p><strong>Background: </strong>Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease associated with high morbidity and mortality worldwide. Oxidative injury and mitochondrial dysfunction in the airway epithelium are major events in COPD progression.</p><p><strong>Methods and results: </strong>The therapeutic effects of Progesterone (P4) were investigated in vivo and in vitro in this study. In vivo, in a cigarette smoke (CS) exposure-induced COPD mouse model, P4 treatment significantly ameliorated CS exposure-induced physiological and pathological characteristics, including inflammatory cell infiltration and oxidative injury, in a dose-dependent manner. The c-MYC/SIRT1/PGC-1α pathway is involved in the protective function of P4 against CS-induced COPD. In vitro, P4 co-treatment significantly ameliorated H₂O₂-induced oxidative injury and mitochondrial dysfunctions by promoting cell proliferation, increasing mitochondrial membrane potential, decreasing ROS levels and apoptosis, and increasing ATP content. Moreover, P4 co-treatment partially attenuated H₂O₂-caused inhibition in Nrf1, Tfam, Mfn1, PGR-B, c-MYC, SIRT1, and PGC-1α levels. In BEAS-2B and ASM cells, the c-MYC/SIRT1 axis regulated P4's protective effects against H₂O₂-induced oxidative injury and mitochondrial dysfunctions.</p><p><strong>Conclusion: </strong>P4 activates the c-MYC/SIRT1 axis, ameliorating CS-induced COPD and protecting both airway epithelial cells and smooth muscle cells against H₂O₂-induced oxidative damage. PGC-1α and downstream mitochondrial signaling pathways might be involved.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11323532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA-binding protein GIGYF2 orchestrates hepatic insulin resistance through STAU1/PTEN-mediated disruption of the PI3K/AKT signaling cascade.","authors":"Ziwei Lv, Yuanyuan Ren, Yang Li, Fanglin Niu, Zhuozhuo Li, Man Li, Xiaofang Li, Qinhua Li, Deqing Huang, Yi Yu, Yuyan Xiong, Lu Qian","doi":"10.1186/s10020-024-00889-6","DOIUrl":"10.1186/s10020-024-00889-6","url":null,"abstract":"<p><strong>Background: </strong>Obesity is well-established as a significant contributor to the development of insulin resistance (IR) and diabetes, partially due to elevated plasma saturated free fatty acids like palmitic acid (PA). Grb10-interacting GYF Protein 2 (GIGYF2), an RNA-binding protein, is widely expressed in various tissues including the liver, and has been implicated in diabetes-induced cognitive impairment. Whereas, its role in obesity-related IR remains uninvestigated.</p><p><strong>Methods: </strong>In this study, we employed palmitic acid (PA) exposure to establish an in vitro IR model in the human liver cancer cell line HepG2 with high-dose chronic PA treatment. The cells were stained with fluorescent dye 2-NBDG to evaluate cell glucose uptake. The mRNA expression levels of genes were determined by real-time qRT-PCR (RT-qPCR). Western blotting was employed to examine the protein expression levels. The RNA immunoprecipitation (RIP) was used to investigate the binding between protein and mRNA. Lentivirus-mediated gene knockdown and overexpression were employed for gene manipulation. In mice, an IR model induced by a high-fat diet (HFD) was established to validate the role and action mechanisms of GIGYF2 in the modulation of HFD-induced IR in vivo.</p><p><strong>Results: </strong>In hepatocytes, high levels of PA exposure strongly trigger the occurrence of hepatic IR evidenced by reduced glucose uptake and elevated extracellular glucose content, which is remarkably accompanied by up-regulation of GIGYF2. Silencing GIGYF2 ameliorated PA-induced IR and enhanced glucose uptake. Conversely, GIGYF2 overexpression promoted IR, PTEN upregulation, and AKT inactivation. Additionally, PA-induced hepatic IR caused a notable increase in STAU1, which was prevented by depleting GIGYF2. Notably, silencing STAU1 prevented GIGYF2-induced PTEN upregulation, PI3K/AKT pathway inactivation, and IR. STAU1 was found to stabilize PTEN mRNA by binding to its 3'UTR. In liver cells, tocopherol treatment inhibits GIGYF2 expression and mitigates PA-induced IR. In the in vivo mice model, GIGYF2 knockdown and tocopherol administration alleviate high-fat diet (HFD)-induced glucose intolerance and IR, along with the suppression of STAU1/PTEN and restoration of PI3K/AKT signaling.</p><p><strong>Conclusions: </strong>Our study discloses that GIGYF2 mediates obesity-related IR by disrupting the PI3K/AKT signaling axis through the up-regulation of STAU1/PTEN. Targeting GIGYF2 may offer a potential strategy for treating obesity-related metabolic diseases, including type 2 diabetes.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11323356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-regulatory potency of USP1 on inflammasome components promotes pyroptosis in thyroid follicular cells and contributes to the progression of Hashimoto's thyroiditis","authors":"Xuying Zhao, Wenyu Ni, Wenjie Zheng, Wenkai Ni, Chunfeng Sun, Yunjuan Gu, Zhifeng Gu","doi":"10.1186/s10020-024-00885-w","DOIUrl":"https://doi.org/10.1186/s10020-024-00885-w","url":null,"abstract":"Inflammatory diseases are often initiated by the activation of inflammasomes triggered by pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs), which mediate pyroptosis. Although pyroptosis resulting from aberrant inflammasome triggering in thyroid follicular cells (TFCs) has been observed in Hashimoto's thyroiditis (HT) patients, the underlying mechanisms remain largely unknown. Given the extensive involvement of protein ubiquitination and deubiquitination in inflammatory diseases, we aimed to investigate how deubiquitinating enzymes regulate thyroid follicular cell pyroptosis and HT pathogenesis. Our study specifically investigated the role of Ubiquitin-specific peptidase 1 (USP1), a deubiquitinase (DUB), in regulating the inflammasome components NLRP3 and AIM2, which are crucial in pyroptosis. We conducted a series of experiments to elucidate the function of USP1 in promoting pyroptosis associated with inflammasomes and the progression of HT. These experiments involved techniques such as USP1 knockdown or inhibition, measurement of key pyroptosis indicators including caspase-1, caspase-1 p20, and GSDMD-N, and examination of the effects of USP1 abrogation on HT using a mouse model. Furthermore, we explored the impact of USP1 on NLRP3 transcription and its potential interaction with p65 nuclear transportation. Our findings provide compelling evidence indicating that USP1 plays a pivotal role in promoting inflammasome-mediated pyroptosis and HT progression by stabilizing NLRP3 and AIM2 through deubiquitination. Furthermore, we discovered that USP1 modulates the transcription of NLRP3 by facilitating p65 nuclear transportation. Knockdown or inhibition of USP1 resulted in weakened cell pyroptosis, as evidenced by reduced levels of caspase-1 p20 and GSDMD-N, which could be restored upon AIM2 overexpression. Remarkably, USP1 abrogation significantly ameliorated HT in the mice model, likely to that treating mice with pyroptosis inhibitors VX-765 and disulfiram. Our study highlights a regulatory mechanism of USP1 on inflammasome activation and pyroptosis in TFCs during HT pathogenesis. These findings expand our understanding of HT and suggest that inhibiting USP1 may be a potential treatment strategy for managing HT.","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141932993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In mouse model of mixed granulocytic asthma with corticosteroid refractoriness, Bronchom mitigates airway hyperresponsiveness, inflammation and airway remodeling.","authors":"Acharya Balkrishna, Sandeep Sinha, Anupam Pandey, Surjeet Singh, Monali Joshi, Rani Singh, Anurag Varshney","doi":"10.1186/s10020-024-00888-7","DOIUrl":"10.1186/s10020-024-00888-7","url":null,"abstract":"<p><strong>Background: </strong>Asthma is a heterogeneous, inflammatory disease with several phenotypes and endotypes. Severe asthmatics often exhibit mixed granulocytosis with reduced corticosteroid sensitivity. Bronchom is a newly developed Ayurvedic prescription medicine, indicated for the treatment of obstructive airway disorders. The purpose of the present study was to evaluate the in-vivo efficacy of Bronchom in mouse model of mixed granulocytic asthma with steroidal recalcitrance.</p><p><strong>Methods: </strong>High-performance thin layer chromatography (HPTLC) and Ultra-high performance liquid chromatography (UHPLC) were employed to identify and quantitate the phytometabolites present in Bronchom. The preclinical effectiveness of Bronchom was assessed in house dust mite (HDM) and Complete Freund's adjuvant (CFA)-induced mixed granulocytic asthma model in mice. High dose of dexamethasone was tested parallelly. Specific-pathogen-free C57BL/6 mice were immunized with HDM and CFA and nineteen days later, they were intranasally challenged with HDM for four consecutive days. Then the mice were challenged with nebulized methacholine to evaluate airway hyperresponsiveness (AHR). Inflammatory cell influx was enumerated in the bronchoalveolar lavage fluid (BALF) followed by lung histology. Additionally, the concentrations of Th2 and pro-inflammatory cytokines was assessed in the BALF by multiplexed immune assay. The mRNA expression of pro-inflammatory cytokines and Mucin 5AC (MUC5AC) was also evaluated in the lung.</p><p><strong>Results: </strong>HPTLC fingerprinting and UHPLC quantification of Bronchom revealed the presence of bioactive phytometabolites, namely, rosmarinic acid, gallic acid, methyl gallate, piperine, eugenol and glycyrrhizin. Bronchom effectively reduced AHR driven by HDM-CFA and the influx of total leukocytes, eosinophils and neutrophils in the BALF. In addition, Bronchom inhibited the infiltration of inflammatory cells in the lung as well as goblet cell metaplasia. Further, it also suppressed the elevated levels of Th2 cytokines and pro-inflammatory cytokines in the BALF. Similarly, Bronchom also regulated the mRNA expression of pro-inflammatory cytokines as well as MUC5AC in mice lungs. Reduced effectiveness of a high dose of the steroid, dexamethasone was observed in the model.</p><p><strong>Conclusions: </strong>We have demonstrated for the first time the robust pharmacological effects of an herbo-mineral medicine in an animal model of mixed granulocytic asthma induced by HDM and CFA. The outcomes suggest the potential utility of Bronchom in severe asthmatics with a mixed granulocytic phenotype.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11318311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting AGTPBP1 inhibits pancreatic cancer progression via regulating microtubules and ERK signaling pathway.","authors":"Ding-Zhong Li, Zhe-Yu Yang, Asi Leng, Qian Zhang, Xiao-Dong Zhang, Yan-Chao Bian, Rui Xiao, Jian-Jun Ren","doi":"10.1186/s10020-024-00892-x","DOIUrl":"10.1186/s10020-024-00892-x","url":null,"abstract":"<p><strong>Background: </strong>AGTPBP1 is a cytosolic carboxypeptidase that cleaves poly-glutamic acids from the C terminus or side chains of α/β tubulins. Although its dysregulated expression has been linked to the development of non-small cell lung cancer, the specific roles and mechanisms of AGTPBP1 in pancreatic cancer (PC) have yet to be fully understood. In this study, we examined the role of AGTPBP1 on PC in vitro and in vivo.</p><p><strong>Methods: </strong>Immunohistochemistry was used to examine the expression of AGTPBP1 in PC and non-cancerous tissues. Additionally, we assessed the malignant behaviors of PC cells following siRNA-mediated AGTPBP1 knockdown both in vitro and in vivo. RNA sequencing and bioinformatics analysis were performed to identify the differentially expressed genes regulated by AGTPBP1.</p><p><strong>Results: </strong>We determined that AGTPBP1 was overexpressed in PC tissues and the higher expression of AGTPBP1 was closely related to the location of tumors. AGTPBP1 inhibition can significantly decrease cell progression in vivo and in vitro. Moreover, the knockdown of AGTPBP1 inhibited the expression of ERK1/2, P-ERK1/2, MYLK, and TUBB4B proteins via the ERK signaling pathway.</p><p><strong>Conclusion: </strong>Our research indicates that AGTPBP1 may be a putative therapeutic target for PC.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11318240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcriptomic analysis reveals a decrease in the frequency of macrophage-RGS1^high subsets in patients with osteoarticular tuberculosis.","authors":"Ying Jiang, Xinqiang Zhang, Bo Wang, Liping Tang, Xin Liu, Xiudong Ding, Yueming Dong, Hong Lei, Di Wang, Huicheng Feng","doi":"10.1186/s10020-024-00886-9","DOIUrl":"10.1186/s10020-024-00886-9","url":null,"abstract":"<p><strong>Background: </strong>Cell subsets differentially modulate host immune responses to Mycobacterium tuberculosis (MTB) infection. However, the nature and functions of these subsets against osteoarticular tuberculosis (OTB) are unclear. Here, we aimed to understand the phenotypes and functions of immune cell subsets in patients with OTB using single-cell RNA sequencing (scRNA-Seq).</p><p><strong>Methods: </strong>Pathological and healthy adjacent tissues were isolated from patients with OTB and subjected to scRNA-Seq. Unsupervised clustering of cells was performed based on gene expression profiles, and uniform manifold approximation and projection was used for clustering visualization.</p><p><strong>Results: </strong>Thirteen cell subsets were identified in OTB tissues. scRNA-seq datasets of patients and healthy controls (HCs) showed that infection changed the frequency of immune cell subsets in OTB tissues. Myeloid cell examination revealed nine subsets. The frequency of macrophage-RGS1^high subsets decreased in OTB tissues; this increased MTB susceptibility in an SLC7A11/ferroptosis-dependent manner. Immunohistochemistry assays and flow cytometry for patients with OTB and osteoarticular bacterial infection (OBI) and HCs verified that the frequency of macrophage-RGS1^high subset decreased in OTB tissues and blood samples, thereby distinguishing patients with OTB from HCs and patients with OBI.</p><p><strong>Conclusion: </strong>The macrophage-RGS1^high subset levels were decreased in patients with OTB, and would be up-regulated after effective treatment. Therefore, the clinical significance of this study is to discover that macrophage-RGS1^high subset may serve as a potential biomarker for OTB diagnosis and treatment efficacy monitoring.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulated lipid metabolism and intervertebral disc degeneration: the important role of ox-LDL/LOX-1 in endplate chondrocyte senescence and calcification.","authors":"Tan Bing, Xiang Shanlin, Wang Jisheng, Hao Jie, Cao Ruichao, Zhang Zhiwei, Yu Bin, Ma Zhaoxin, Hu Zhenming, Zhou Nian","doi":"10.1186/s10020-024-00887-8","DOIUrl":"10.1186/s10020-024-00887-8","url":null,"abstract":"<p><strong>Background: </strong>Lipid metabolism disorders are associated with degeneration of multiple tissues and organs, but the mechanism of crosstalk between lipid metabolism disorder and intervertebral disc degeneration (IDD) has not been fully elucidated. In this study we aim to investigate the regulatory mechanism of abnormal signal of lipid metabolism disorder on intervertebral disc endplate chondrocyte (EPC) senescence and calcification.</p><p><strong>Methods: </strong>Human intervertebral disc cartilage endplate tissue, cell model and rat hyperlipemia model were performed in this study. Histology and immunohistochemistry were used to human EPC tissue detection. TMT-labelled quantitative proteomics was used to detect differential proteins, and MRI, micro-CT, safranin green staining and immunofluorescence were performed to observe the morphology and degeneration of rat tail intervertebral discs. Flow cytometry, senescence-associated β-galactosidase staining, alizarin red staining, alkaline phosphatase staining, DCFH-DA fluorescent probe, and western blot were performed to detect the expression of EPC cell senescence, senescence-associated secretory phenotype, calcification-related proteins and the activation of cell senescence-related signaling pathways.</p><p><strong>Results: </strong>Our study found that the highly expressed oxidized low-density lipoprotein (ox-LDL) and Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) in human degenerative EPC was associated with hyperlipidemia (HLP). TMT-labelled quantitative proteomics revealed enriched pathways such as cell cycle regulation, endochondral bone morphogenesis and inflammation. The rat model revealed that HLP could induce ox-LDL, LOX-1, senescence and calcification markers high expression in EPC. Moreover, we demonstrated that ox-LDL-induced EPCs senescence and calcification were dependent on the LOX-1 receptor, and the ROS/P38-MAPK/NF-κB signaling pathway was implicated in the regulation of senescence induced by ox-LDL/LOX-1 in cell model.</p><p><strong>Conclusions: </strong>So our study revealed that ox-LDL/LOX-1-induced EPCs senescence and calcification through ROS/P38-MAPK/NF-κB signaling pathway, providing information on understanding the link between lipid metabolism disorders and IDD.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11311918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD74 facilitates immunotherapy response by shaping the tumor microenvironment of hepatocellular carcinoma.","authors":"Jianghong Cheng, Junyang Li, Xinjie Jiang, Xi Ma, Bixuan Li, Han Zhai, Xianyang Luo, Yi Zhou, Junhua Wu, Zhiming Zhang, Shuai Chen, Yang Wang","doi":"10.1186/s10020-024-00884-x","DOIUrl":"10.1186/s10020-024-00884-x","url":null,"abstract":"<p><strong>Background: </strong>CD74 is ectopically expressed in many tumors and can regulate tumor immunity. However, there are many gaps in the study of the prognostic value of CD74 expression and immune infiltration in hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>An online tumor database was searched to obtain data on gene/protein expression. Immune infiltration analysis was performed using the Tumor Immune Estimation Resource and Comprehensive Analysis on Multi-Omics of Immunotherapy in Pan-cancer databases. Single-cell data were obtained from the Tissue-specific Gene Expression and Regulation, Single-cell Transcriptomes of Tumor Immune Microenvironment and Tumor Immune Single-cell Hub 2 databases.</p><p><strong>Results: </strong>CD74 was highly expressed in HCC patients. HCC patients with high CD74 expression who consumed alcohol or were negative for hepatitis virus had a better prognosis than patients with low CD74 expression. CD74 was mainly enriched in immune response regulation pathways. Both copy number variations in CD74 and CD74 expression patterns affected the infiltration levels of immune cells. Interestingly, CD74 regulated the differentiation of myeloid cells. CD74 in macrophages and dendritic cells (DCs) forms complex networks with malignant cells and hepatic progenitor cell (HPC)-like cells, respectively. High CD74 expression in HPC-like cells and malignant cells significantly decreased the fraction of C-type lectin domain family 9 A (CLEC9A)-cDC1⁺ DCs and IL-1B⁺ macrophages, respectively. Their crosstalk subsequently shaped the tumor microenvironment of HCC, possibly through the CD74-MIF axis. Importantly, patients with high CD74 expression presented higher immune scores and achieved good outcomes after receiving immunotherapy.</p><p><strong>Conclusion: </strong>High CD74 expression is associated with the abundance of a variety of immune cell types, mediating interactions among tumor and immune cells and shaping the malignant behavior of HCC. In summary, CD74 may be a hallmark for determining the prognosis and immune cell infiltration levels of HCC patients.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11308498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stellate cells are in utero markers of pancreatic disease in cystic fibrosis.","authors":"Shih-Hsing Leir, Svyatoslav Tkachenko, Alekh Paranjapye, Frederick Meckler, Arnaud J Van Wettere, Jenny L Kerschner, Elizabeth Kuznetsov, Makayla Schacht, Pulak Gillurkar, Misha Regouski, Iuri Viotti Perisse, Cheyenne M Marriott, Ying Liu, Ian Bunderson, Kenneth L White, Irina A Polejaeva, Ann Harris","doi":"10.1186/s10020-024-00871-2","DOIUrl":"10.1186/s10020-024-00871-2","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic fibrosis is an early diagnostic feature of the common inherited disorder cystic fibrosis (CF). Many people with CF (pwCF) are pancreatic insufficient from birth and the replacement of acinar tissue with cystic lesions and fibrosis is a progressive phenotype that may later lead to diabetes. Little is known about the initiating events in the fibrotic process though it may be a sequela of inflammation in the pancreatic ducts resulting from loss of CFTR impairing normal fluid secretion. Here we use a sheep model of CF (CFTR^-/-) to examine the evolution of pancreatic disease through gestation.</p><p><strong>Methods: </strong>Fetal pancreas was collected at six time points from 50-days of gestation through to term, which is equivalent to ~ 13 weeks to term in human. RNA was extracted from tissue for bulk RNA-seq and single cells were prepared from 80-day, 120-day and term samples for scRNA-seq. Data were validated by immunochemistry.</p><p><strong>Results: </strong>Transcriptomic evidence from bulk RNA-seq showed alterations in the CFTR^-/- pancreas by 65-days of gestation, which are accompanied by marked pathological changes by 80-days of gestation. These include a fibrotic response, confirmed by immunostaining for COL1A1, αSMA and SPARC, together with acinar loss. Moreover, using scRNA-seq we identify a unique cell population that is significantly overrepresented in the CFTR^-/- animals at 80- and 120-days gestation, as are stellate cells at term.</p><p><strong>Conclusion: </strong>The transcriptomic changes and cellular imbalance that we observe likely have pivotal roles in the evolution of CF pancreatic disease and may provide therapeutic opportunities to delay or prevent pancreatic destruction in CF.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11304907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLUT5-overexpression-related tumorigenic implications.","authors":"Nikola Hadzi-Petrushev, Radoslav Stojchevski, Anastasija Jakimovska, Mimoza Stamenkovska, Slavica Josifovska, Aleksandar Stamatoski, Iliyana Sazdova, Ramadan Sopi, Andre Kamkin, Hristo Gagov, Mitko Mladenov, Dimiter Avtanski","doi":"10.1186/s10020-024-00879-8","DOIUrl":"10.1186/s10020-024-00879-8","url":null,"abstract":"<p><p>Glucose transporter 5 (GLUT5) overexpression has gained increasing attention due to its profound implications for tumorigenesis. This manuscript provides a comprehensive overview of the key findings and implications associated with GLUT5 overexpression in cancer. GLUT5 has been found to be upregulated in various cancer types, leading to alterations in fructose metabolism and enhanced glycolysis, even in the presence of oxygen, a hallmark of cancer cells. This metabolic shift provides cancer cells with an alternative energy source and contributes to their uncontrolled growth and survival. Beyond its metabolic roles, recent research has unveiled additional aspects of GLUT5 in cancer biology. GLUT5 overexpression appears to play a critical role in immune evasion mechanisms, which further worsens tumor progression and complicates therapeutic interventions. This dual role of GLUT5 in both metabolic reprogramming and immune modulation highlights its significance as a potential diagnostic marker and therapeutic target. Understanding the molecular mechanisms driving GLUT5 overexpression is crucial for developing targeted therapeutic strategies that can disrupt the unique vulnerabilities of GLUT5-overexpressing cancer cells. This review emphasizes the complexities surrounding GLUT5's involvement in cancer and underscores the pressing need for continued research to unlock its potential as a diagnostic biomarker and therapeutic target, ultimately improving cancer management and patient outcomes.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11304774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}