Biochemistry and Biophysics Reports最新文献

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Biochemical strategies for opioid-sparing pain management in the operating room
IF 2.3
Biochemistry and Biophysics Reports Pub Date : 2025-01-25 DOI: 10.1016/j.bbrep.2025.101927
Fatemeh Hosseinzadeh , Alireza Nourazarian
{"title":"Biochemical strategies for opioid-sparing pain management in the operating room","authors":"Fatemeh Hosseinzadeh ,&nbsp;Alireza Nourazarian","doi":"10.1016/j.bbrep.2025.101927","DOIUrl":"10.1016/j.bbrep.2025.101927","url":null,"abstract":"<div><div>The opioid epidemic has highlighted the increasing need for alternative pain relievers in surgical settings. This review explores non-opioid approaches for managing pain in the ever-changing operating room. The review examines the molecular basis of pain perception, with a focus on receptor-targeted treatments that offer effectiveness without the risks associated with opioids. Despite the demonstrated benefits and improved side effect profiles, our literature analysis reveals the challenges that hinder the integration of innovative pain relievers. We explore the potential of neuroimmune modulators, peptide disruptors, and new neurotransmitter analogs in the quest for effective pain relief, paving the way for a future of anesthesia without opioids.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101927"},"PeriodicalIF":2.3,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143144330","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}
引用次数: 0
A comprehensive review of molecular hydrogen as a novel nutrition therapy in relieving oxidative stress and diseases: Mechanisms and perspectives
IF 2.3
Biochemistry and Biophysics Reports Pub Date : 2025-01-25 DOI: 10.1016/j.bbrep.2025.101933
Fatmanur Yıldız , Tyler W. LeBaron , Duried Alwazeer
{"title":"A comprehensive review of molecular hydrogen as a novel nutrition therapy in relieving oxidative stress and diseases: Mechanisms and perspectives","authors":"Fatmanur Yıldız ,&nbsp;Tyler W. LeBaron ,&nbsp;Duried Alwazeer","doi":"10.1016/j.bbrep.2025.101933","DOIUrl":"10.1016/j.bbrep.2025.101933","url":null,"abstract":"<div><div>Oxidative stress is responsible for the pathogenesis of many diseases, and antioxidants are commonly included in their treatment protocols. Over the past two decades, numerous biomedical reports have revealed the therapeutic benefits of molecular hydrogen (H<sub>2</sub>) in relieving oxidation-related diseases. H<sub>2</sub> has been found to have selective antioxidant properties against the most dangerous oxidants (hydroxyl radicals and peroxynitrite). H<sub>2</sub> demonstrates numerous biologically therapeutic properties, including anti-inflammatory, antioxidant, anti-cancer, anti-stress, anti-apoptotic, anti-allergic effects, signaling molecule functions, regulation of redox balance, modulation of antioxidant enzyme gene expression, improvement of blood vessel function, down-regulation of pro-inflammatory cytokines, stimulation of energy metabolism, and protection of the nervous system. Experimental and clinical studies have shown the potential use of hydrogen nutrition therapy for ameliorating various diseases, including cardiovascular, respiratory, and metabolic disorders, as well as obesity, gastrointestinal disorders, and brain and nervous system disorders. The administration methods of hydrogen include inhalation, hydrogen-rich water, hydrogen-rich saline, hydrogen-rich eye drops, and hydrogen-rich bathing. Hydrogen nutritional therapy can be applied to different diseases, and it offers a natural alternative to chemical and radiation therapies. This review covers the different administration methods and the latest experimental and clinical research on the potential applications of H<sub>2</sub> in nutritional therapy for different diseases.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101933"},"PeriodicalIF":2.3,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143144331","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}
引用次数: 0
Development of a general anti-viral therapeutic using cholestosome technology to exploit inhibition of intracellular viral production
IF 2.3
Biochemistry and Biophysics Reports Pub Date : 2025-01-23 DOI: 10.1016/j.bbrep.2025.101922
Lawrence Mielnicki , Julie Hughes , Mary Irving , Mary McCourt
{"title":"Development of a general anti-viral therapeutic using cholestosome technology to exploit inhibition of intracellular viral production","authors":"Lawrence Mielnicki ,&nbsp;Julie Hughes ,&nbsp;Mary Irving ,&nbsp;Mary McCourt","doi":"10.1016/j.bbrep.2025.101922","DOIUrl":"10.1016/j.bbrep.2025.101922","url":null,"abstract":"<div><div>The recent events of the worldwide Covid-19 pandemic showed the need for a general anti-viral therapeutic, independent of the specific characteristics of the virus, that targets intracellular mechanisms of viral production to prevent the rapid, overwhelming spread of infection and its devastating consequences. The development of the Cholestosome technology, a drug delivery system made exclusively of cholesteryl esters, is a solution for intracellular targeting of viral replication. It is well known that Zn<sup>2+</sup> is capable of inhibiting viral replication but the control of intracellular Zn<sup>2+</sup> concentration is tightly regulated. Cholestosome technology can encapsulate Zn<sup>2+</sup> and deliver it to cells to inhibit viral replication. The human betacoronavirus OC43 (OC43) model system was used to infect cells and infected cells were treated with Zn<sup>2+</sup> encapsulated in Cholestosomes as well as appropriate controls. Viral production was measured using CPE as well as PCR methods to determine inhibition of infection. Experimental results indicated a 55 % reduction in viral load for those cells treated with Zn<sup>2+</sup> encapsulated in cholestosomes versus Zn<sup>2+</sup> alone.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101922"},"PeriodicalIF":2.3,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143143994","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}
引用次数: 0
Identifying Hub Genes and Pathways in Pancreatic Ductal Adenocarcinoma (PAAD): A comprehensive in silico study
IF 2.3
Biochemistry and Biophysics Reports Pub Date : 2025-01-22 DOI: 10.1016/j.bbrep.2025.101921
Elham Karimi , Niloufar Sadat Kalaki , Seyed Mohammad Akrami
{"title":"Identifying Hub Genes and Pathways in Pancreatic Ductal Adenocarcinoma (PAAD): A comprehensive in silico study","authors":"Elham Karimi ,&nbsp;Niloufar Sadat Kalaki ,&nbsp;Seyed Mohammad Akrami","doi":"10.1016/j.bbrep.2025.101921","DOIUrl":"10.1016/j.bbrep.2025.101921","url":null,"abstract":"<div><h3>Background</h3><div>One of the most aggressive tumors is pancreatic ductal adenocarcinoma (PAAD), which is usually discovered at an advanced stage and is linked to a poor response to current treatment options and a significant risk of metastasis.</div></div><div><h3>Methods</h3><div>The Gene Expression Omnibus (GEO) database selected GSE15471, GSE28735, GSE62165, and GSE16515. Differentially expressed genes (DEGs) were defined as having a logFC of &gt;1 and ≤ −1 and an adjusted p-value of less than 0.05. Differentially expressed genes (DEGs) from the four datasets were identified using the GEO2R tool. KEGG and GO databases were used to identify related pathways. PPIs were analyzed using Cytoscape and Gephi. A GEPIA analysis confirmed the target genes.</div></div><div><h3>Results</h3><div>The analysis of protein-protein interactions (PPI) along with data from the Gene Expression Omnibus (GEO) led to the identification of 66 hub genes and 819 common differentially expressed genes (DEGs). GO and KEGG pathway analyses indicated that these DEGs are significantly associated with functions related to cell adhesion, extracellular exosomes, structural components of the extracellular matrix, and the cytoskeleton in muscle cells. The expression levels of 8 genes—FN1, CXCR4, MMP9, PXDN, CBS, ALB, GPT2, and EGF—demonstrated a notable difference between normal and tumor samples, as identified through GEPIA analysis.</div></div><div><h3>Conclusion</h3><div>The hub genes and related pathways that are connected to the development of PAAD were found in this study. These genes could serve as promising diagnostic biomarkers, offering a valuable chance to detect PAAD in its initial stages, leading to more effective treatment options.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101921"},"PeriodicalIF":2.3,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143143343","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}
引用次数: 0
Oxidative stress-induced NCC activation in the development of nocturnal polyuria in mice: Therapeutic potential of a sustained hydrogen-releasing silicon-based agent
IF 2.3
Biochemistry and Biophysics Reports Pub Date : 2025-01-20 DOI: 10.1016/j.bbrep.2025.101923
Yosuke Sekii , Hiroshi Kiuchi , Kentaro Takezawa , Norichika Ueda , Takahiro Imanaka , Sohei Kuribayashi , Koichi Okada , Shinichiro Fukuhara , Ryoichi Imamura , Hiromistu Negoro , Yuki Kobayashi , Hikaru Kobayashi , Norio Nonomura
{"title":"Oxidative stress-induced NCC activation in the development of nocturnal polyuria in mice: Therapeutic potential of a sustained hydrogen-releasing silicon-based agent","authors":"Yosuke Sekii ,&nbsp;Hiroshi Kiuchi ,&nbsp;Kentaro Takezawa ,&nbsp;Norichika Ueda ,&nbsp;Takahiro Imanaka ,&nbsp;Sohei Kuribayashi ,&nbsp;Koichi Okada ,&nbsp;Shinichiro Fukuhara ,&nbsp;Ryoichi Imamura ,&nbsp;Hiromistu Negoro ,&nbsp;Yuki Kobayashi ,&nbsp;Hikaru Kobayashi ,&nbsp;Norio Nonomura","doi":"10.1016/j.bbrep.2025.101923","DOIUrl":"10.1016/j.bbrep.2025.101923","url":null,"abstract":"<div><div>Nocturnal polyuria is a prevalent condition associated with significant deterioration in quality of life and increased risk of mortality. Despite its clinical relevance, the underlying pathogenesis is poorly understood, and existing therapies have limited efficacy. A recent study in mouse model revealed that overactivation of the intrarenal SPAK (STE20/SPS1-related proline–alanine rich protein kinase)–sodium chloride co-transporter (NCC) pathway in the distal renal tubule is a crucial mechanism contributing to nocturnal polyuria. Here, we demonstrate that increased oxidative stress in the kidney activates the NCC, leading to insufficient sodium excretion during the active period and compensatory sodium excretion during the inactive period, resulting in polyuria during the inactive period. In addition, we show that a newly developed antioxidant—a silicon component agent—reduced oxidative stress and inhibited NCC activation, resulting in the amelioration of polyuria during the inactive period. These findings highlight the critical contributions of intrarenal oxidative stress to the pathogenesis of nocturnal polyuria and suggest that silicon-based agent holds promise for clinical application as a novel treatment for nocturnal polyuria.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101923"},"PeriodicalIF":2.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078525","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}
引用次数: 0
Integrative analysis of RNA-Seq data and machine learning approaches to identify Biomarkers for Rhizoctonia solani resistance in sugar beet
IF 2.3
Biochemistry and Biophysics Reports Pub Date : 2025-01-19 DOI: 10.1016/j.bbrep.2025.101920
Bahman Panahi , Mahdi Hassani , Nahid Hosseinzaeh Gharajeh
{"title":"Integrative analysis of RNA-Seq data and machine learning approaches to identify Biomarkers for Rhizoctonia solani resistance in sugar beet","authors":"Bahman Panahi ,&nbsp;Mahdi Hassani ,&nbsp;Nahid Hosseinzaeh Gharajeh","doi":"10.1016/j.bbrep.2025.101920","DOIUrl":"10.1016/j.bbrep.2025.101920","url":null,"abstract":"<div><div>Rhizoctonia solani is a significant pathogen that causes crown and root rot in sugar beet (Beta vulgaris), leading to considerable yield losses. To develop resilient cultivars, it is crucial to understand the molecular mechanisms underlying both resistance and susceptibility. In this study, we employed RNA-Seq analysis alongside machine learning techniques to identify key biomarkers associated with resistance to R. solani. We ranked differentially expressed genes (DEGs) using feature-weighting algorithms, such as Relief and kernel-based methods, to model expression patterns between sensitive and tolerant cultivars. Our integrative approach identified several candidate genes, including Bv5g001004 (encoding Ethylene-responsive transcription factor 1A), Bv8g000842 (encoding 5′-adenylylsulfate reductase 1), and Bv7g000949 (encoding Heavy metal-associated isoprenylated plant protein 5). These genes are involved in stress signal transduction, sulfur metabolism, and disease resistance pathways. Graphical visualizations of the Random Forest and Decision Tree models illustrated the decision-making processes and gene interactions, enhancing our understanding of the complex relationships between sensitive and tolerant genotypes. This study demonstrates the effectiveness of integrating RNA-Seq and machine learning techniques for biomarker discovery and highlights potential targets for developing R. solani-resistant sugar beet cultivars. The findings provide a robust framework for improving crop enhancement strategies and contribute to sustainable agricultural practices by increasing stress resilience in economically important crops.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101920"},"PeriodicalIF":2.3,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078520","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}
引用次数: 0
Hepatic HSD17B6 is dispensable for diet-induced fatty liver disease in mice
IF 2.3
Biochemistry and Biophysics Reports Pub Date : 2025-01-19 DOI: 10.1016/j.bbrep.2025.101924
Delong Yuan , Nan Bai , Qihan Zhu , Shaoxuan Song , Anyuan He , Jianqing Wang , Yali Chen
{"title":"Hepatic HSD17B6 is dispensable for diet-induced fatty liver disease in mice","authors":"Delong Yuan ,&nbsp;Nan Bai ,&nbsp;Qihan Zhu ,&nbsp;Shaoxuan Song ,&nbsp;Anyuan He ,&nbsp;Jianqing Wang ,&nbsp;Yali Chen","doi":"10.1016/j.bbrep.2025.101924","DOIUrl":"10.1016/j.bbrep.2025.101924","url":null,"abstract":"<div><div>Metabolic dysfunction-associated fatty liver disease (MAFLD) affects up to a third of the global population, which causes huge both clinical and economic burdens. However, its therapeutic strategy is still limited. Steroid dysregulation plays a pivotal role in the homeostasis of lipid metabolism. 17-beta-hydroxysteroid dehydrogenase type 6 (HSD17B6)—one member of 17β-HSDs, encoded by the gene <em>Hsd17b6</em>, catalyzes the synthesis of androsterone and estrone—steroid hormones. However, whether the manipulation of HSD17B6 could ameliorate diet-induced fatty liver disease remains unknown. Here, we found that the expression of <em>Hsd17b6</em> is enriched in the liver in both humans and mice. The data of single-cell RNA-seq suggests that <em>Hsd17b6</em> appears to be exclusively expressed in hepatocytes—the parenchymal cells of the liver. Furthermore, the hepatic expression of <em>Hsd17b6</em> is correlated with fatty liver disease. A mouse model with <em>Hsd17b6</em> deletion in the liver (HLKO) is successfully generated via the administration of AAV8 expressing Cre recombinase (driven by TBG—a liver-specific promoter) and sgRNAs of <em>Hsd17b6</em> to Cre-dependent Cas9 mice. Control and HLKO mice were challenged with the high-fat choline-deficient diet—a diet widely used for the model generation of fatty liver disease. Interestingly, the HLKO liver shows a special proteome signature, with the altered proteins enriched in the Golgi apparatus. However, the deletion of <em>Hsd17b6</em> does not affect fatty liver disease in terms of fat accumulation, inflammation, and hepatic fibrosis. Taken together, our study suggests that the expression of <em>Hsd17b6</em> is enriched in the liver and correlated with fatty liver disease but its hepatic deletion does not affect diet-induced fatty liver disease.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101924"},"PeriodicalIF":2.3,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078457","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}
引用次数: 0
Single-cell RNA sequencing provides new insights into the interaction between astrocytes and neurons after spinal cord injury in mice
IF 2.3
Biochemistry and Biophysics Reports Pub Date : 2025-01-18 DOI: 10.1016/j.bbrep.2025.101917
Zhi Tang , Hengyang Lu , Xiao Yang , Mao Wu , Junfeng Yang , Shaoshuo Li , Heng Liu , Junkang Zhou , Bin Tang , Xinyao Du , Fei Xu , Yang Shao , Jianwei Wang
{"title":"Single-cell RNA sequencing provides new insights into the interaction between astrocytes and neurons after spinal cord injury in mice","authors":"Zhi Tang ,&nbsp;Hengyang Lu ,&nbsp;Xiao Yang ,&nbsp;Mao Wu ,&nbsp;Junfeng Yang ,&nbsp;Shaoshuo Li ,&nbsp;Heng Liu ,&nbsp;Junkang Zhou ,&nbsp;Bin Tang ,&nbsp;Xinyao Du ,&nbsp;Fei Xu ,&nbsp;Yang Shao ,&nbsp;Jianwei Wang","doi":"10.1016/j.bbrep.2025.101917","DOIUrl":"10.1016/j.bbrep.2025.101917","url":null,"abstract":"<div><h3>Background</h3><div>Spinal cord injury (SCI) is a devastating neurological disease in which astrocytes play a central role. Understanding the relationship between different subtypes of astrocytes and neuron subtypes during the progression of SCI is critical to understanding the disease.</div></div><div><h3>Methods and results</h3><div>In this study, single-cell RNA sequencing (scRNA-seq) was used to analyze the transcriptome data of acute, subacute and intermediate stages of SCI in mice as well as normal tissues. Different subtypes of astrocytes and neuronal cells were identified and their dynamic changes and functionalities during the development of SCI. An intriguing discovery was the identification of a specific subtype of astrocytes characterized by unique expression of Gap43, Vim, Aldoc, and Mt1. This subtype of cells shows similarities in gene expression with neurons and potentially transitioned into neurons during the course of SCI. Furthermore, we have uncovered the important role of the glycolytic pathway in this cellular transformation process. Furthermore, through cellular interaction analysis, we validated pathways (mdk-ptprz1,ptn-ptprz1,ptn-sdc3) associated with the potential conversion of these specific cell subsets into neurons. Finally, these cells were observed by fluorescence microscopy and critical gene expressions were validated by Western blot.</div></div><div><h3>Conclusions</h3><div>The results of this study not only deepen our understanding of the mechanisms underlying SCI, but also provide new insights and opportunities for the development of novel therapeutic strategies and interventions.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101917"},"PeriodicalIF":2.3,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078550","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}
引用次数: 0
Resistance to FLT3 inhibitors involves different molecular mechanisms and reduces new DNA synthesis
IF 2.3
Biochemistry and Biophysics Reports Pub Date : 2025-01-16 DOI: 10.1016/j.bbrep.2024.101894
Jingmei Yang, Ran Friedman
{"title":"Resistance to FLT3 inhibitors involves different molecular mechanisms and reduces new DNA synthesis","authors":"Jingmei Yang,&nbsp;Ran Friedman","doi":"10.1016/j.bbrep.2024.101894","DOIUrl":"10.1016/j.bbrep.2024.101894","url":null,"abstract":"<div><div>Acute myeloid leukaemia (AML) is a hard to treat blood cancer. Mutations in FLT3 are common among the genetic aberrations that characterise the cancer. Patients initially react to FLT3 inhibitors but drug resistance is a hinder to successful therapy. To better understand the mechanisms leading to drug resistance, we generated four AML cell lines resistant to the inhibitors gilteritinib or FF-10101, and explored their resistance mechanisms. We further tested whether the novel inhibitor Chen-9u could be used to limit cell growth. The results showed that each of the four resistant cell lines became resistant through a different mechanism. Resistant cells showed decreased FLT3 and increased NRAS pathway activity and reduced DNA synthesis due to decrease in CDK4 activity. Resistance mechanisms included resistance mutations in FLT3 (C695F and N701K), and a novel mutation in NRAS (G12C). In a fourth line, resistance might have developed through a MYCN mutation. Cell growth was inhibited by Chen-9u and resistant clones could not be obtained with this inhibitor. The results highlight opportunities and limitations. On the one hand, resistant cells were produced due to different mechanisms, showing the versatility of tumour cells. Furthermore, resistance developed to the most advanced inhibitors, one of which is covalent and the other non-covalent but highly specific. On the other hand, it is shown that DNA synthesis is reduced, which means that resistance has evolutionary consequences. Finally, the novel drug-resistant cell lines may serve as useful models for better understanding of the cellular events associated with inherent and acquired drug resistance.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101894"},"PeriodicalIF":2.3,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078537","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}
引用次数: 0
Screening of biomarkers for diagnosing chronic kidney disease and heart failure with preserved ejection fraction through bioinformatics analysis
IF 2.3
Biochemistry and Biophysics Reports Pub Date : 2025-01-11 DOI: 10.1016/j.bbrep.2024.101911
Can Hou , Jiayi Xu , Min Zhou , Junyu Huo , Xiaofei Wang , Wanying Jiang , Tong Su , Hui Wang , Fang Jia
{"title":"Screening of biomarkers for diagnosing chronic kidney disease and heart failure with preserved ejection fraction through bioinformatics analysis","authors":"Can Hou ,&nbsp;Jiayi Xu ,&nbsp;Min Zhou ,&nbsp;Junyu Huo ,&nbsp;Xiaofei Wang ,&nbsp;Wanying Jiang ,&nbsp;Tong Su ,&nbsp;Hui Wang ,&nbsp;Fang Jia","doi":"10.1016/j.bbrep.2024.101911","DOIUrl":"10.1016/j.bbrep.2024.101911","url":null,"abstract":"<div><h3>Background</h3><div>Previous research has established that chronic kidney disease (CKD) and heart failure with preserved ejection fraction (HFpEF) often coexist. Although we have a preliminary understanding of the potential correlation between HFpEF and CKD, the underlying pathophysiological mechanisms remain unclear. This study aimed to elucidate the molecular mechanisms associated with CKD and HFpEF through bioinformatics analysis.</div></div><div><h3>Methods</h3><div>Datasets for HFpEF and CKD were obtained from the Gene Expression Omnibus (GEO) database. The R software package “limma” was employed to conduct differential expression analysis. Functional annotation was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). We conducted weighted gene co-expression network analysis (WGCNA), correlation analysis with autophagy, ferroptosis, and immune-related processes, as well as transcriptional regulation analysis, immune infiltration analysis, and diagnostic performance evaluation. Finally, the diagnostic potential of the identified hub genes for CKD and HFpEF was assessed using ROC curve analysis (GSE37171).</div></div><div><h3>Results</h3><div>Differential expression analysis revealed 58 overlapping genes, comprised of 40 up-regulated and 18 down-regulated genes. Both GO and KEGG analyses indicated enriched pathways relevant to both disorders. WGCNA identified 4086 genes associated with CKD. Further comparison with differentially expressed genes (DEGs) identified three hub genes (KLF4, SCD, and SEL1L3) that were linked to autophagy, ferroptosis, and immune processes in both conditions. Additionally, a miRNA-mRNA regulatory network involving 376 miRNAs and 12 transcription factors (TFs) was constructed. ROC curve analysis was performed to evaluate the diagnostic utility of the hub genes for CKD and HFpEF.</div></div><div><h3>Conclusion</h3><div>This study elucidated shared pathogenic mechanisms and identified diagnostic markers common to both HFpEF and CKD. The identified hub genes show promise as potential tools for early diagnosis and treatment strategies for these conditions.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"41 ","pages":"Article 101911"},"PeriodicalIF":2.3,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057888","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}
引用次数: 0
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