Journal of Cellular and Molecular Medicine最新文献

{"title":"Antimalarial drug discovery against malaria parasites through haplopine modification: An advanced computational approach","authors":"Shopnil Akash,&nbsp;Guendouzi Abdelkrim,&nbsp;Imren Bayil,&nbsp;Md. Eram Hosen,&nbsp;Nobendu Mukerjee,&nbsp;Abdullah F. Shater,&nbsp;Fayez M. Saleh,&nbsp;Ghadeer M. Albadrani,&nbsp;Muath Q. Al-Ghadi,&nbsp;Mohamed M. Abdel-Daim,&nbsp;Tuğba Taşkin Tok","doi":"10.1111/jcmm.17940","DOIUrl":"10.1111/jcmm.17940","url":null,"abstract":"<p>The widespread emergence of antimalarial drug resistance has created a major threat to public health. Malaria is a life-threatening infectious disease caused by <i>Plasmodium</i> spp., which includes Apicoplast DNA polymerase and <i>Plasmodium falciparum</i> cysteine protease falcipain-2. These components play a critical role in their life cycle and metabolic pathway, and are involved in the breakdown of erythrocyte hemoglobin in the host, making them promising targets for anti-malarial drug design. Our current study has been designed to explore the potential inhibitors from haplopine derivatives against these two targets using an in silico approach. A total of nine haplopine derivatives were used to perform molecular docking, and the results revealed that Ligands 03 and 05 showed strong binding affinity compared to the control compound atovaquone. Furthermore, these ligand-protein complexes underwent molecular dynamics simulations, and the results demonstrated that the complexes maintained strong stability in terms of RMSD (root mean square deviation), RMSF (root mean square fluctuation), and Rg (radius of gyration) over a 100 ns simulation period. Additionally, PCA (principal component analysis) analysis and the dynamic cross-correlation matrix showed positive outcomes for the protein-ligand complexes. Moreover, the compounds exhibited no violations of the Lipinski rule, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions yielded positive results without indicating any toxicity. Finally, density functional theory (DFT) and molecular electrostatic potential calculations were conducted, revealing that the mentioned derivatives exhibited better stability and outstanding performance. Overall, this computational approach suggests that these haplopine derivatives could serve as a potential source for developing new, effective antimalarial drugs to combat malaria. However, further in vitro or in vivo studies might be conducted to determine their actual effectiveness.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 20","pages":"3168-3188"},"PeriodicalIF":5.3,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17940","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41126537","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":"Correction to Chronic stress inhibits testosterone synthesis in Leydig cells through mitochondrial damage via Atp5a1","authors":"","doi":"10.1111/jcmm.17829","DOIUrl":"10.1111/jcmm.17829","url":null,"abstract":"<p>In Xiaofan Xiong et al,<span>¹</span> the spots number of ‘224’ and ‘246’ in Figure 3B mismatch with the spots of ‘234’ and ‘236’ in Figure 3C due to technical error. In addition, the spots name of ‘246’ in Table 1 mismatch with the spots of ‘236’ in Figure 3C. The correct Figure 3 and Table 1 are shown below. The authors confirmed that all results and conclusions of this article remain unchanged.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 20","pages":"3213-3214"},"PeriodicalIF":5.3,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17829","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10363181","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":"Correction to Down-regulated lncRNA SLC25A5-AS1 facilitates cell growth and inhibits apoptosis via miR-19a-3p/PTEN/PI3K/AKT signalling pathway in gastric cancer","authors":"","doi":"10.1111/jcmm.17830","DOIUrl":"10.1111/jcmm.17830","url":null,"abstract":"<p>In Xiwen Li et al.,<span>¹</span> the colony formation analyses for BGC-823 (vector) and SGC-7901 of Figure 3B are incorrect. In addition, the labels for BGC-823 and SGC-7901 are reverse in Figure 3E. The correct figures are shown below. The authors confirm that all results and conclusions of this article remain unchanged.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 20","pages":"3215-3216"},"PeriodicalIF":5.3,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17830","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10314667","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":"Demystifying the impact of prenatal tobacco exposure on the placental immune microenvironment: Avoiding the tragedy of mending the fold after death","authors":"Xiaoxuan Zhao,&nbsp;Yuepeng Jiang,&nbsp;Xiao Ma,&nbsp;Qujia Yang,&nbsp;Xinyi Ding,&nbsp;Hanzhi Wang,&nbsp;Xintong Yao,&nbsp;Linxi Jin,&nbsp;Qin Zhang","doi":"10.1111/jcmm.17846","DOIUrl":"10.1111/jcmm.17846","url":null,"abstract":"Prenatal tobacco exposure (PTE) correlates significantly with a surge in adverse pregnancy outcomes, yet its pathological mechanisms remain partially unexplored. This study aims to meticulously examine the repercussions of PTE on placental immune landscapes, employing a coordinated research methodology encompassing bioinformatics, machine learning and animal studies. Concurrently, it aims to screen biomarkers and potential compounds that could sensitively indicate and mitigate placental immune disorders. In the course of this research, two gene expression omnibus (GEO) microarrays, namely GSE27272 and GSE7434, were included. Gene set enrichment analysis (GSEA) and immune enrichment investigations on differentially expressed genes (DEGs) indicated that PTE might perturb numerous innate or adaptive immune‐related biological processes. A cohort of 52 immune‐associated DEGs was acquired by cross‐referencing the DEGs with gene sets derived from the ImmPort database. A protein–protein interaction (PPI) network was subsequently established, from which 10 hub genes were extracted using the maximal clique centrality (MCC) algorithm (JUN, NPY, SST, FLT4, FGF13, HBEGF, NR0B2, AREG, NR1I2, SEMA5B). Moreover, we substantiated the elevated affinity of tobacco reproductive toxicants, specifically nicotine and nitrosamine, with hub genes through molecular docking (JUN, FGF13 and NR1I2). This suggested that these genes could potentially serve as crucial loci for tobacco's influence on the placental immune microenvironment. To further elucidate the immune microenvironment landscape, consistent clustering analysis was conducted, yielding three subtypes, where the abundance of follicular helper T cells (p &lt; 0.05) in subtype A, M2 macrophages (p &lt; 0.01), neutrophils (p &lt; 0.05) in subtype B and CD8+ T cells (p &lt; 0.05), resting NK cells (p &lt; 0.05), M2 macrophages (p &lt; 0.05) in subtype C were significantly different from the control group. Additionally, three pivotal modules, designated as red, blue and green, were identified, each bearing a close association with differentially infiltrated immunocytes, as discerned by the weighted gene co‐expression network analysis (WGCNA). Functional enrichment analysis was subsequently conducted on these modules. To further probe into the mechanisms by which immune‐associated DEGs are implicated in intercellular communication, 20 genes serving as ligands or receptors and connected to differentially infiltrating immunocytes were isolated. Employing a variety of machine learning techniques, including one‐way logistic regression, LASSO regression, random forest and artificial neural networks, we screened 11 signature genes from the intersection of immune‐associated DEGs and secretory protein‐encoding genes derived from the Human Protein Atlas. Notably, CCL18 and IFNA4 emerged as prospective peripheral blood markers capable of identifying PTE‐induced immune disorders. These markers demonstrated impressive predictive power, as indicated ","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 20","pages":"3026-3052"},"PeriodicalIF":5.3,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17846","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10590231","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":"Therapeutic effects of medicinal plants and their constituents on lung cancer, in vitro, in vivo and clinical evidence","authors":"Arghavan Memarzia,&nbsp;Saeideh Saadat,&nbsp;Fereshteh Asgharzadeh,&nbsp;Sepide Behrouz,&nbsp;Gert Folkerts,&nbsp;Mohammad Hossein Boskabady","doi":"10.1111/jcmm.17936","DOIUrl":"10.1111/jcmm.17936","url":null,"abstract":"<p>The most common type of cancer in the world is lung cancer. Traditional treatments have an important role in cancer therapy. In the present review, the most recent findings on the effects of medicinal plants and their constituents or natural products (NP) in treating lung cancer are discussed. Empirical studies until the end of March 2022 were searched using the appropriate keywords through the databases PubMed, Science Direct and Scopus. The extracts and essential oils tested were all shown to effect lung cancer by several mechanisms including decreased tumour weight and volume, cell viability and modulation of cytokine. Some plant constituents increased expression of apoptotic proteins, the proportion of cells in the G2/M phase and subG0/G1 phase, and Cyt c levels. Also, natural products (NP) activate apoptotic pathways in lung cancer cell including p-JNK, Akt/mTOR, PI3/ AKT and Bax, Bcl2, but suppressed AXL phosphorylation. Plant-derived substances altered the cell morphology, reduced cell migration and metastasis, oxidative marker production, p-eIF2α and GRP78, IgG, IgM levels and reduced leukocyte counts, LDH, GGT, 5′NT and carcinoembryonic antigen (CEA). Therefore, medicinal plant extracts and their constituents could have promising therapeutic value for lung cancer, especially if used in combination with ordinary anti-cancer drugs.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 19","pages":"2841-2863"},"PeriodicalIF":5.3,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17936","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10268334","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":"Combinations of EGFR and MET inhibitors reduce proliferation and invasiveness of mucosal melanoma cells","authors":"Aleksandra Simiczyjew,&nbsp;Justyna Wądzyńska,&nbsp;Magdalena Kot,&nbsp;Marcin Ziętek,&nbsp;Rafał Matkowski,&nbsp;Mai P. Hoang,&nbsp;Piotr Donizy,&nbsp;Dorota Nowak","doi":"10.1111/jcmm.17935","DOIUrl":"10.1111/jcmm.17935","url":null,"abstract":"<p>Mucosal melanoma (MM) is a very rare and aggressive type of cancer for which immunotherapy or targeted therapy such as BRAF/MEK inhibitors, used in cutaneous melanoma, usually fail. Due to our earlier experience showing the high effectiveness of epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (MET) inhibitors in reducing the activation of the MAPK and PI3K/AKT signalling pathways, we aim to test whether these drugs would also be effective for mucosal melanoma. Cells representing two commercially available mucosal melanoma cell lines (GAK and HMVII) and one cell line obtained from a patient's vaginal melanoma were treated with MET or EGFR inhibitors, or combinations of these agents. The dual-inhibitor treatment strategy resulted in a decrease of cell proliferation, migration and invasion. Moreover, combinations of inhibitors led to reduction of pEGFR/EGFR and pMET/MET ratio and downregulation of PI3K/AKT and MEK/ERK1/2-based signalling pathways. Our findings indicate a potential therapeutic strategy based on EGFR and MET inhibitors in mucosal melanoma, which should be further evaluated in vivo and in clinical experiments. They also suggest that targeting multiple receptor tyrosine kinases may block signalling crosstalk and possibly delay the appearance of resistance to kinase inhibitors in mucosal melanoma cells.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 19","pages":"2995-3008"},"PeriodicalIF":5.3,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17935","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10238829","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":"The role of regulatory T cells in the pathogenesis of acute kidney injury","authors":"Xiaoyou Liu,&nbsp;Jianmin Hu,&nbsp;Guorong Liao,&nbsp;Ding Liu,&nbsp;Song Zhou,&nbsp;Jie Zhang,&nbsp;Jun Liao,&nbsp;Zefeng Guo,&nbsp;Yuzhu Li,&nbsp;Siqiang Yang,&nbsp;Shichao Li,&nbsp;Hua Chen,&nbsp;Ying Guo,&nbsp;Min Li,&nbsp;Lipei Fan,&nbsp;Liuyang Li,&nbsp;Ming Zhao,&nbsp;Yongguang Liu","doi":"10.1111/jcmm.17771","DOIUrl":"10.1111/jcmm.17771","url":null,"abstract":"<p>The incidence of acute kidney injury (AKI) is on the rise and is associated with high mortality; however, there are currently few effective treatments. Moreover, the relationship between Tregs and other components of the immune microenvironment (IME) in the pathogenesis of AKI remains unclear. We downloaded four publicly accessible AKI datasets, GSE61739, GSE67401, GSE19130, GSE81741, GSE19288 and GSE106993 from the gene expression omnibus (GEO) database. Additionally, we gathered two kidney single-cell sequencing (scRNA-seq) samples from the Department of Organ Transplantation at Zhujiang Hospital of Southern Medical University to investigate chronic kidney transplant rejection (CKTR). Moreover, we also collected three samples of normal kidney tissue from GSE131685. By analysing the differences in immune cells between the AKI and Non-AKI groups, we discovered that the Non-AKI group contained a significantly greater number of Tregs than the AKI group. Additionally, the activation of signalling pathways, such as inflammatory molecules secretion, immune response, glycolytic metabolism, NOTCH, FGF, NF-κB and TLR4, was significantly greater in the AKI group than in the Non-AKI group. Additionally, analysis of single-cell sequencing data revealed that Tregs in patients with chronic kidney rejection and in normal kidney tissue have distinct biology, including immune activation, cytokine production, and activation fractions of signalling pathways such as NOTCH and TLR4. In this study, we found significant differences in the IME between AKI and Non-AKI, including differences in Tregs cells and activation levels of biologically significant signalling pathways. Tregs were associated with lower activity of signalling pathways such as inflammatory response, inflammatory molecule secretion, immune activation, glycolysis.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 20","pages":"3202-3212"},"PeriodicalIF":5.3,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17771","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10155301","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":"Design and preclinical testing of an anti-CD41 CAR T cell for the treatment of acute megakaryoblastic leukaemia","authors":"Adrian Bogdan Tigu,&nbsp;Catalin Sorin Constantinescu,&nbsp;Patric Teodorescu,&nbsp;David Kegyes,&nbsp;Raluca Munteanu,&nbsp;Richard Feder,&nbsp;Mareike Peters,&nbsp;Ioana Pralea,&nbsp;Cristina Iuga,&nbsp;Diana Cenariu,&nbsp;Andra Marcu,&nbsp;Alina Tanase,&nbsp;Anca Colita,&nbsp;Rares Drula,&nbsp;Jon Thor Bergthorsson,&nbsp;Victor Greiff,&nbsp;Delia Dima,&nbsp;Cristina Selicean,&nbsp;Ioana Rus,&nbsp;Mihnea Zdrenghea,&nbsp;Diana Gulei,&nbsp;Gabriel Ghiaur,&nbsp;Ciprian Tomuleasa","doi":"10.1111/jcmm.17810","DOIUrl":"10.1111/jcmm.17810","url":null,"abstract":"<p>Acute megakaryoblastic leukaemia (AMkL) is a rare subtype of acute myeloid leukaemia (AML) representing 5% of all reported cases, and frequently diagnosed in children with Down syndrome. Patients diagnosed with AMkL have low overall survival and have poor outcome to treatment, thus novel therapies such as CAR T cell therapy could represent an alternative in treating AMkL. We investigated the effect of a new CAR T cell which targets CD41, a specific surface antigen for M7-AMkL, against an in vitro model for AMkL, DAMI Luc2 cell line. The performed flow cytometry evaluation highlighted a percentage of 93.8% CAR T cells eGFP-positive and a limited acute effect on lowering the target cell population. However, the interaction between effector and target (E:T) cells, at a low ratio, lowered the cell membrane integrity, and reduced the M7-AMkL cell population after 24 h of co-culture, while the cytotoxic effect was not significant in groups with higher E:T ratio. Our findings suggest that the anti-CD41 CAR T cells are efficient for a limited time spawn and the cytotoxic effect is visible in all experimental groups with low E:T ratio.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 19","pages":"2864-2875"},"PeriodicalIF":5.3,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17810","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10210389","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":"Effects of blocking CD24 and CD47 ‘don't eat me’ signals in combination with rituximab in mantle-cell lymphoma and chronic lymphocytic leukaemia","authors":"Andrea Aroldi,&nbsp;Mario Mauri,&nbsp;Daniele Ramazzotti,&nbsp;Matteo Villa,&nbsp;Federica Malighetti,&nbsp;Valentina Crippa,&nbsp;Federica Cocito,&nbsp;Chiara Borella,&nbsp;Elisa Bossi,&nbsp;Carolina Steidl,&nbsp;Chiara Scollo,&nbsp;Claudia Voena,&nbsp;Roberto Chiarle,&nbsp;Luca Mologni,&nbsp;Rocco Piazza,&nbsp;Carlo Gambacorti-Passerini","doi":"10.1111/jcmm.17868","DOIUrl":"10.1111/jcmm.17868","url":null,"abstract":"<p>Mantle-cell lymphoma (MCL) is a B-cell non-Hodgkin Lymphoma (NHL) with a poor prognosis, at high risk of relapse after conventional treatment. MCL-associated tumour microenvironment (TME) is characterized by M2-like tumour-associated macrophages (TAMs), able to interact with cancer cells, providing tumour survival and resistance to immuno-chemotherapy. Likewise, monocyte-derived nurse-like cells (NLCs) present M2-like profile and provide proliferation signals to chronic lymphocytic leukaemia (CLL), a B-cell malignancy sharing with MCL some biological and phenotypic features. Antibodies against TAMs targeted CD47, a ‘don't eat me’ signal (DEMs) able to quench phagocytosis by TAMs within TME, with clinical effectiveness when combined with Rituximab in pretreated NHL. Recently, CD24 was found as valid DEMs in solid cancer. Since CD24 is expressed during B-cell differentiation, we investigated and identified consistent CD24 in MCL, CLL and primary human samples. Phagocytosis increased when M2-like macrophages were co-cultured with cancer cells, particularly in the case of paired DEMs blockade (i.e. anti-CD24 + anti-CD47) combined with Rituximab. Similarly, unstimulated CLL patients-derived NLCs provided increased phagocytosis when DEMs blockade occurred. Since high levels of CD24 were associated with worse survival in both MCL and CLL, anti-CD24-induced phagocytosis could be considered for future clinical use, particularly in association with other agents such as Rituximab.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 20","pages":"3053-3064"},"PeriodicalIF":5.3,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17868","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10126627","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":"Effects of early exercise on cardiac function and lipid metabolism pathway in heart failure","authors":"Sérgio Luiz Borges de Souza,&nbsp;Gustavo Augusto Ferreira Mota,&nbsp;Vitor Loureiro da Silva,&nbsp;Danielle Fernandes Vileigas,&nbsp;Paula Grippa Sant'Ana,&nbsp;Cristina Schmitt Gregolin,&nbsp;Rebeca Lopes Figueira,&nbsp;Sabrina Setembre Batah,&nbsp;Alexandre Todorovic Fabro,&nbsp;Gilson Masahiro Murata,&nbsp;Silmeia Garcia Zanati Bazan,&nbsp;Marina Politi Okoshi,&nbsp;Antonio Carlos Cicogna","doi":"10.1111/jcmm.17908","DOIUrl":"10.1111/jcmm.17908","url":null,"abstract":"<p>We employed an early training exercise program, immediately after recovery from surgery, and before severe cardiac hypertrophy, to study the underlying mechanism involved with the amelioration of cardiac dysfunction in aortic stenosis (AS) rats. As ET induces angiogenesis and oxygen support, we aimed to verify the effect of exercise on myocardial lipid metabolism disturbance. Wistar rats were divided into Sham, trained Sham (ShamT), AS and trained AS (AST). The exercise consisted of 5-week sessions of treadmill running for 16 weeks. Statistical analysis was conducted by <span>anova</span> or Kruskal–Wallis test and Goodman test. A global correlation between variables was also performed using a two-tailed Pearson's correlation test. AST rats displayed a higher functional capacity and a lower cardiac remodelling and dysfunction when compared to AS, as well as the myocardial capillary rarefaction was prevented. Regarding metabolic properties, immunoblotting and enzymatic assay raised beneficial effects of exercise on fatty acid transport and oxidation pathways. The correlation assessment indicated a positive correlation between variables of angiogenesis and FA utilisation, as well as between metabolism and echocardiographic parameters. In conclusion, early exercise improves exercise tolerance and attenuates cardiac structural and functional remodelling. In parallel, exercise attenuated myocardial capillary and lipid metabolism derangement in rats with aortic stenosis-induced heart failure.</p>","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 19","pages":"2956-2969"},"PeriodicalIF":5.3,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17908","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10126629","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}