JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"Energy Metabolism Profiling of Human Colorectal Tumours","authors":"Leenu Reinsalu,&nbsp;Sten Miller,&nbsp;Giuseppe Leonardo Auditano,&nbsp;Marju Puurand,&nbsp;Rafael Moreno-Sanchez,&nbsp;Emma Saavedra,&nbsp;Vahur Valvere,&nbsp;Tuuli Käämbre","doi":"10.1111/jcmm.70462","DOIUrl":"https://doi.org/10.1111/jcmm.70462","url":null,"abstract":"<p>Colorectal cancer (CRC) is a significant global health burden, and its early detection is crucial. Novel diagnostic and prognostic methods are required for improving patient treatment, survival and quality of life. One promising approach is the analysis and understanding of the metabolic reprogramming undergone by cancer cells. Here, by analysing the changes in transcript and protein contents, activities, pathway flux and energy metabolite ratios in post-operative CRC tumours, in comparison to adjacent healthy tissue, the energy metabolism was characterised at the molecular and functional levels. Greater expression of glucose transporter 1 and lactate dehydrogenase A (LDH), together with increased protein content and activity of LDH in tumours, suggested a higher glycolytic capability. Hexokinase transcripts, protein and activity were similar, whereas monocarboxylate transport transcripts and protein contents were lower in tumours. The creatine kinase transcripts and the adenylate kinase protein contents were lower in tumours, suggesting a functional decrease in the CRC energy transfer pathway. Notwithstanding this, oxidative phosphorylation was fully functional and exhibited higher catalytic efficiency (<i>Vmax</i>/<i>Km</i>_ADP) in tumours, whereas the cellular energy charge was slightly lower in tumours. Remarkably, higher OxPhos catalytic efficiency correlated with advancing CRC clinical stage. The data revealed that CRC tumours exhibit a hybrid energy metabolism phenotype where both glycolysis and oxidative phosphorylation are highly active.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70462","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YBX1 Modulates Intimal Hyperplasia by Regulating Expression and Alternative Splicing of Cell Cycle Associated Genes in RASMCs","authors":"Yi Huang,&nbsp;Yuheng Wang,&nbsp;Feng Zhu,&nbsp;Chao Guo,&nbsp;Xinyang Zhang,&nbsp;Yiqing Li,&nbsp;Yunfei Chen,&nbsp;Chuanqi Cai,&nbsp;Dan Shang","doi":"10.1111/jcmm.70445","DOIUrl":"https://doi.org/10.1111/jcmm.70445","url":null,"abstract":"<p>YBX1, a DNA-/RNA-binding protein, is implicated in various diseases, yet its role in intimal hyperplasia (IH) remains unclear. This study investigates YBX1's function in rat aortic smooth muscle cells (RASMCs) through knockdown experiments. Results show that YBX1 knockdown reduces cell proliferation and migration while inducing apoptosis. ELISA and western blot analyses revealed increased levels of the anti-inflammatory factor IL10 and markers for phenotypic transformation, Calponin and Myocardin. Transcriptome sequencing identified 1598 differentially expressed genes (DEGs), with 347 upregulated and 1251 downregulated. Upregulated DEGs were linked to pathways like ECM–receptor interaction and Wnt signalling, while downregulated genes involved cell cycle and p53 signalling. Additionally, 629 significant alternative splicing events were noted, primarily affecting pathways related to cell division and migration. Integrated analysis of YBX1-bound RNAs and RNA-seq data highlighted key DEGs, such as CCNB1 and TPM1, which are crucial for vascular cell behaviour. This study underscores YBX1's vital role in RASMCs and suggests potential therapeutic targets for IH treatment.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70445","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage A2aR Alleviates LPS-Induced Vascular Endothelial Injury and Inflammation via Inhibiting M1 Polarisation and Oxidative Stress","authors":"Yanxiu Li,&nbsp;Tingzhen Chen,&nbsp;Iokfai Cheang,&nbsp;Peiben Liu,&nbsp;Lin Zhao,&nbsp;Xiaoxin He,&nbsp;Yuxi Jin,&nbsp;Mingmin Tang,&nbsp;Zhongqi Zhang,&nbsp;Chengyu Sheng,&nbsp;Zhongwen Zhang,&nbsp;Xiangrong Zuo","doi":"10.1111/jcmm.70458","DOIUrl":"https://doi.org/10.1111/jcmm.70458","url":null,"abstract":"<p>Vascular inflammation and endothelial dysfunction secondary to unchecked activation of endothelium are key mechanisms underlying sepsis and organ failure. However, the intrinsic processes that mitigate excessive endothelial cell activation remain incompletely understood. To determine the central role of adenosine A2a receptor (A2aR) on macrophages in modulating lipopolysaccharide (LPS)-induced vascular endothelial dysfunction, we constructed macrophage A2aR-conditional knockout (Mac-A2aR KO) mice, and stimulated the mice and macrophages with LPS. A2aR agonist, CGS21680, was administered to these models to further explore its impact. Results showed that knockout of Macrophage A2aR exacerbated LPS-induced vascular permeability, oedema, inflammatory cardiac damage and upregulated expression of intercellular adhesion molecule-1 (ICAM-1) and E-selectin in cardiopulmonary vascular endothelium. Moreover, deletion of A2aR on macrophages also markedly aggravated LPS-induced increases in reactive oxygen species (ROS) and declines in antioxidant enzyme gene mRNA and protein expression levels related to oxidative stress (OS). Furthermore, deficiency of A2aR in bone marrow-derived macrophages (BMDMs) promotes LPS-induced macrophage M1 polarisation and secretion of inflammatory cytokines, especially tumour necrosis factor-alpha (TNF-α). Conversely, the pretreatment with CGS21680 in vivo and in vitro showed corresponding improvement in functions of vascular endothelial dysfunction. These data demonstrate that A2aR in macrophages represents a promising novel therapeutic target for LPS-induced uncontrolled vascular endothelial injury and inflammation potentially through reducing macrophage M1 polarisation and OS and inhibiting the production and release of TNF-α production.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70458","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic and Therapeutic Significance of Cancer-Associated Fibroblasts Genes in Osteosarcoma Based on Bulk and Single-Cell RNA Sequencing Data","authors":"Yukang Que,&nbsp;Tianming Ding,&nbsp;Huming Wang,&nbsp;Shenglin Xu,&nbsp;Peng He,&nbsp;Qiling Shen,&nbsp;Kun Cao,&nbsp;Yang Luo,&nbsp;Yong Hu","doi":"10.1111/jcmm.70424","DOIUrl":"https://doi.org/10.1111/jcmm.70424","url":null,"abstract":"<p>Osteosarcoma (OS) is the most frequent primary solid malignancy of bone, whose course is usually dismal without efficient treatments. The aim of the study was to discover novel risk models to more accurately predict and improve the prognosis of patients with osteosarcoma. The single-cell RNA sequencing (scRNA-seq) data was obtained from the GEO database. Bulk RNA-seq data and microarray data of OS were obtained from the TARGET and GEO databases respectively. A clustering tree was plotted to classify all cells into different clusters. The “cellchat” R package was used to establish and visualise cell–cell interaction networks. Then Univariate COX regression analysis was used to determine the prognostic CAF-related genes, followed by the Lasso-Cox regression analysis to build a risk on the prognostic CAF-related genes. Finally, from multiple perspectives, the signature was validated as an accurate and dependable tool in predicting the prognosis and guiding treatment therapies in OS patients. From the single-cell dataset, six OS patients and 46,544 cells were enrolled. All cells were classified into 22 clusters, and the clusters were annotated to 14 types of cells. Subsequently, CAFs were observed as a vital TME components. In cell–cell interaction networks in OS cells, CAFs had a profound impact as four roles. Via the Univariate COX regression analysis, 14 CAF-related genes were screened out. By the Lasso-Cox regression analyses, 11 key CAF-related genes were obtained, based on which an 11-gene signature that could predict the prognosis of osteosarcoma patients was constructed. According to the median of risk scores, all patients were grouped in to the high- and low-risk group, and their overall survival, activated pathways, immune cell infiltrations, and drug sensitivity were significantly differential, which may have important implications for the clinical treatment of patients with osteosarcoma. Our study, a systematic analysis of gene and regulatory genes, has proven that CAF-related genes had excellent diagnostic and prognostic capabilities in OS, and it may reshape the TME in OS. The novel CAF-related risk signature can effectively predict the prognosis of OS and provide new strategies for cancer treatment.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70424","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Laminarin Alleviates Acute Lung Injury Induced by LPS Through Inhibition of M1 Macrophage Polarisation","authors":"Liming Zeng,&nbsp;Jieyu Zhang,&nbsp;Rongrong Song,&nbsp;Xinhuai Dong,&nbsp;Zibo Wei,&nbsp;Xiaoyan Li,&nbsp;Xiaokang Zeng,&nbsp;Jie Yao","doi":"10.1111/jcmm.70440","DOIUrl":"https://doi.org/10.1111/jcmm.70440","url":null,"abstract":"<p>The lipopolysaccharide-induced acute lung injury (ALI) mouse model is used to simulate human acute respiratory distress syndrome (ARDS), which has a high mortality rate. An imbalance between M1 and M2 macrophages, characterised by an increase in M1 macrophages, was observed in sepsis-induced ALI. We report that laminarin, an active ingredient found in algae, exhibits exceptional performance in a mouse model of sepsis-induced ALI. It ameliorates lung edema, enhances the survival rate of mice and reduces the levels of the inflammatory factors TNF-α and IL-6. Furthermore, laminarin reduced the expression of CD86, which are markers associated with M1 macrophages. Laminarin treatment reduces the secretion of TNF-α and IL-6 in LPS-stimulated macrophages. Laminarin treatment also decreases glucose uptake in LPS-stimulated macrophages. Transcriptome sequencing reveals that genes downregulated in LPS-stimulated macrophages following laminarin treatment are predominantly enriched in the HIF-1α signalling pathway. Experimental validation confirms that laminarin treatment of LPS-stimulated macrophages reduces the expression of HIF-1α and significantly decreases the expression of related indicators ROS and NLRP3. After using siRNA to knock down HIF-1α in RAW264.7 cells, the inhibitory effect of laminarin on LPS-induced M1 polarisation of macrophages is abolished. This suggests that laminarin may potentially inhibit macrophage polarisation towards the M1 phenotype by downregulating the HIF-1α signal. In conclusion, the data presented in our study demonstrate that laminarin can effectively reduce M1 macrophage polarisation by downregulating HIF-1α signalling. This makes it a novel candidate drug for the treatment of LPS-induced ALI.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70440","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SERS-Based Assessment of DNA Methylation for the Evaluation of Measurable Residual Disease in Acute Promyelocytic Leukaemia","authors":"Anamaria Bancos,&nbsp;Stefania D. Iancu,&nbsp;Vlad Moisoiu,&nbsp;Alexandra Ghiaur,&nbsp;Adrian Bogdan Tigu,&nbsp;Cristina Buran,&nbsp;Georgiana Ion,&nbsp;Camelia Stancioaica,&nbsp;Bogdan Ionescu,&nbsp;Mihaela Dragomir,&nbsp;Codruta F. Buldus,&nbsp;Diana Cenariu,&nbsp;Madalina Nistor,&nbsp;David Kegyes,&nbsp;Diana Gulei,&nbsp;Nicolae Leopold,&nbsp;Daniel Coriu,&nbsp;Ciprian Tomuleasa","doi":"10.1111/jcmm.70244","DOIUrl":"https://doi.org/10.1111/jcmm.70244","url":null,"abstract":"<p>Acute promyelocytic leukaemia (APL) is a type of acute myeloid leukaemia characterised by the reciprocal translocation t(15;17), which offers a unique possibility for measurable residual disease (MRD) monitoring by PCR amplification of the <i>PML-RARA</i> transcripts. Surface-enhanced Raman scattering (SERS) is a laser molecular spectroscopy technique that allows the rapid analysis of changes in the DNA methylation pattern associated with malignant transformation. In this study involving 49 DNA samples from bone marrow aspirations from patients with APL, we showed that the DNA from MRD-positive samples exhibited lower SERS intensities of the band at 730 cm⁻¹ attributed to adenine. Next, we used the scores derived from principal component analysis (PCA) as input data for machine learning algorithms trained to categorise SERS spectra based on MRD status. The results showed that the highest classification accuracy was achieved by logistic regression, yielding an area under the ROC curve (AUROC) of 0.90. In addition, PCA showed that samples corresponding to patients with FLT3-ITD mutations had a tendency for unsupervised clustering irrespective of MRD status. These results suggest that SERS analysis of DNA represents a promising method for the MRD monitoring of APL patients. Future validation of these findings in large prospective studies is warranted.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70244","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decrypting the Possible Mechanistic Role of Fenofibrate in Alzheimer's Disease and Type 2 Diabetes: The Truth and Mystery","authors":"Mansour A. Alsaleem,&nbsp;Hayder M. Al-Kuraishy,&nbsp;Ali I. Al-Gareeb,&nbsp;Maha M. Abdel-Fattah,&nbsp;Mohammed Alrouji,&nbsp;Nasser A. Al-Harchan,&nbsp;Mubarak Alruwaili,&nbsp;Marios Papadakis,&nbsp;Athanasios Alexiou,&nbsp;Gaber El-Saber Batiha","doi":"10.1111/jcmm.70378","DOIUrl":"https://doi.org/10.1111/jcmm.70378","url":null,"abstract":"<p>Alzheimer's disease (AD) is a neurodegenerative disease caused by the progressive deposition of extracellular amyloid beta (Aβ) and intracellular neurofibrillary tangles (NFTs). Of note, metabolic disorders such as insulin resistance (IR) and type 2 diabetes (T2D) are associated with the development of brain IR and associated neurodegeneration. In addition, AD neuropathology and linked cognitive impairment accelerate the development of peripheral IR and the progression of T2D. Therefore, there is a bidirectional relationship between T2D and AD. It has been demonstrated that AD and T2D induce dysregulation of peroxisome proliferator-activated receptor alpha (PPAR-α) leading to the central and peripheral metabolic disturbances. Hence, dysregulated PPAR-α could be a shared mechanism in both AD and T2D, and restoration of PPAR-α signalling by PPAR-α agonist fenofibrate (FN) may alleviate T2D and AD. Therefore, this review aims to shed light on the potential involvement of PPAR-α in T2D and AD, and how FN could be effective in the management of AD. FN seems to be effective in both AD and T2D by dual neuroprotective and antidiabetic effects that can mitigate AD neuropathology and T2D-related complications by modulating various cellular processes and inflammatory signalling pathways. In conclusion, FN could be a possible candidate in the management of AD and T2D by modulating different signalling pathways involved in the pathogenesis of these conditions.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70378","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to: Letter to Editor by Saravanan Sampoornam et al.","authors":"Shukoofeh Torabi,&nbsp;Faezeh Shekari,&nbsp;Mustapha Najimi,&nbsp;Massoud Vosough","doi":"10.1111/jcmm.70465","DOIUrl":"https://doi.org/10.1111/jcmm.70465","url":null,"abstract":"&lt;p&gt;We appreciate the comments raised in the letter to the editor [&lt;span&gt;1&lt;/span&gt;] which contribute to a deeper understanding of extracellular vesicle characterisation and mechanisms of action. We strongly believe that enhanced transparency is crucial for the reproducibility of our findings and for advancing research in this field [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;In our study, the conditioned medium of WJ-MSCs was collected and then concentrated 10 times using a tangential flow filtration system and centrifuged at a low speed (3000 × &lt;i&gt;g&lt;/i&gt; for 10 min at 4°C) to remove cellular debris from the concentrated medium. This partially clarified medium was then subjected to centrifugal forces in the range of 20,000–110,000 × &lt;i&gt;g&lt;/i&gt; to isolate two subpopulations: EV20K and EV110K [&lt;span&gt;3&lt;/span&gt;]. Regarding EV characterisation, we believe that the most authoritative references for validation parameters are MISEV2018 and MISEV2023 guidelines [&lt;span&gt;4&lt;/span&gt;]. Accordingly, we adhere to these guidelines to ensure robust and reproducible results. These guidelines recommend that one or a combination of the following methods can be used to quantify EVs (particle number, protein and/or lipid content) as well as to directly measure their size [nanoparticle tracking analysis (NTA) and dynamic light scattering (DLS)] [&lt;span&gt;4&lt;/span&gt;]. Each particle size analysis method has some advantages and drawbacks. For instance, even though NTA enables EV characterisation by both size and concentration, several factors can affect NTA results, including lipoprotein contamination, the number of freeze/thaw cycles, sample filtration, video length and particle density per frame [&lt;span&gt;5&lt;/span&gt;]. Since DLS is more user-friendly and provides results more quickly than other methods [&lt;span&gt;6&lt;/span&gt;], EV size distribution was determined using DLS, whereas EV concentration was estimated using total protein quantification.&lt;/p&gt;&lt;p&gt;For labelling EVs, several dyes with unique characteristics can be used, including PKH, DiD and calceins. PKH and DiD are lipophilic dyes that exhibit a strong fluorescent signal when incorporated into EV membranes. Despite the excellent stability of both dyes for long-term tracking, some challenges are associated with these dye-binding assays. These challenges include lipoprotein contamination in EV samples, binding non-specifically to all cell membrane fragments and non-intact EVs, dissociation from EVs into blood and serum components and false positive signals due to self-aggregation and the formation of micelles by dyes that have the same size and morphology similar to EVs [&lt;span&gt;7, 8&lt;/span&gt;]. To overcome these challenges, the cellular uptake and integrity of EVs have been evaluated using membrane-impermeable fluorescent dyes like calceins. These fluorescent dyes can only identify metabolically active and intact vesicles since they require intracellular esterases to release calcein and become fluorescent [&lt;span&gt;9&lt;/span&gt;]. EV labelling procedures were performed for","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70465","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantification of All-Trans Retinoic Acid and Cytokine Levels After Fungal, Viral and Bacterial Infections in the Lung","authors":"Samuel A. Krug,&nbsp;Ravineel Singh,&nbsp;Jianshi Yu,&nbsp;William T. Witt,&nbsp;Nageswara R. Pilli,&nbsp;Angela Wilks,&nbsp;Mariette Barbier,&nbsp;Keven M. Robinson,&nbsp;Maureen A. Kane","doi":"10.1111/jcmm.70391","DOIUrl":"https://doi.org/10.1111/jcmm.70391","url":null,"abstract":"<p>All-<i>trans</i> retinoic acid (atRA) plays a critical role in tissue homeostasis as a master regulator of cellular proliferation, apoptosis and differentiation as well as in immune cell differentiation and function. An active metabolite of vitamin A, atRA has been reported to be reduced in a number of inflammatory conditions in both the lung and gut. Decreases in atRA have been reported in gastrointestinal tissue in inflammatory bowel diseases, radiation-induced gastrointestinal injury and viral infection. In the lung, atRA is reduced in inflammatory conditions including allergic asthma and radiation-induced lung injury; however, the impact of infection on lung atRA is not well defined. In this short communication, we quantified atRA and cytokine levels in the lung after fungal, viral and bacterial infections in mice and determined the correlation between atRA and cytokine levels in the lung. atRA was quantified by LC-MRM³, and seven different inflammatory cytokines were quantified by multiplexed immunoassay in mouse lung challenged with Influenza A, <i>Aspergillus fumigatus</i>, <i>Pseudomonas aeruginosa</i> or methicillin-resistant <i>Staphylococcus aureus</i>. Combined infections were also investigated. Our results show that there is a significant decrease in atRA after infection regardless of infection type. We show an inverse correlation between the decrease in atRA and the increase in inflammatory cytokines IL-1β, IL-6, IL-10 and IL-12 in lung tissue during infection. Elucidation of the homeostatic regulation of active metabolite atRA is important to understanding disease pathology and may enable future drug development to combat the effects of inflammation and infection.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70391","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143533305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Growth Hormone on Branched-Chain Amino Acids Catabolism in Males With Hypopituitarism","authors":"Yuwen Zhang,&nbsp;Zhiqiu Ye,&nbsp;Enfei Xiang,&nbsp;Peizhan Chen,&nbsp;Xuqian Fang","doi":"10.1111/jcmm.70451","DOIUrl":"https://doi.org/10.1111/jcmm.70451","url":null,"abstract":"<p>To investigate the impact of growth hormone (GH) on branched-chain amino acids (BCAAs) catabolism in males with hypopituitarism, we measured the concentration of amino acids in 133 males with hypopituitarism and 90 age-matched healthy controls using untargeted metabolome. A rat model of hypopituitarism was established through hypophysectomy, followed by recombinant human GH (rhGH) intervention. Targeted metabolomics and label-free quantitative phosphoproteomics were utilised to assess amino acid levels in rats and explore the mechanisms of GH's effect on BCAA catabolism. Hypopituitarism exhibited elevated concentrations of BCAAs, which correlated positively with triglyceride, fasting insulin and HOMA-IR. The BCAAs were significantly elevated following hypophysectomy and were substantially reduced upon rhGH intervention. Phosphorylation proteomics analysis in liver tissues revealed that differentially expressed phosphoproteins (DEPPs) after GH treatment were predominantly involved in ‘RNA metabolic process’, ‘Diseases of signal transduction by growth factor receptors’ and ‘BCAAs degradation’. Notably, 12 proteins in the BCAA degradation pathway showed altered phosphorylation without whole protein changes. Importantly, the expression or phosphorylation modification of BCKDH, BCATs and MuRF1 were restored through rhGH intervention. Hypopituitarism exhibits elevated levels of circulating BCAAs. The increased circulating BCAAs in hypopituitarism may result from enhanced MuRF1-mediated muscle proteolysis, which greatly exceeds the BCAA degradation capacity. This study provides valuable insights into the effects of GH on BCAA catabolism at the scale of the proteomics level.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70451","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143533471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}