International Journal of Molecular Sciences最新文献

{"title":"Molecular Docking Studies and In Vitro Activity of Pancreatic Lipase Inhibitors from Yak Milk Cheese.","authors":"Peng Wang, Xuemei Song, Qi Liang","doi":"10.3390/ijms26020756","DOIUrl":"10.3390/ijms26020756","url":null,"abstract":"<p><p>Pancreatic lipase serves as a primary trigger for hyperlipidemia and is also a crucial target in the inhibition of hypercholesterolemia. By synthesizing anti-hypercholesterolemic drugs such as atorvastatin, which are used to treat hypercholesterolemia, there were some side effects associated with the long-term use of statins. Based on this idea, in the present study, we identified peptides that inhibited PL by virtual screening and in vitro activity assays. In addition, to delve into the underlying mechanisms, we undertook a dual investigative approach involving both molecular docking analyses and molecular dynamics simulations. The results showed that peptides RK7, KQ7, and TL9, all with molecular weights of <1000 Da and a high proportion of hydrophobic amino acids, inhibited PL well. Molecular docking and molecular dynamics showed that peptides RK7, KQ7, and TL9 bound to important amino acid residues of PL, such as Pro and Leu, through hydrogen bonding, hydrophobic interactions, salt bridges, and π-π stacking to occupy the substrate-binding site, which inhibited PL and identified them as potential PL inhibitors. In vitro tests showed that the IC₅₀ of RK7 and KQ7 on PL were 0.690 mg/mL and 0.593 mg/mL, respectively, and the inhibitory effects of RK7 and KQ7 on PL were significantly enhanced after simulated gastrointestinal digestion. Our results suggested that peptides RK7 and KQ7 from yak milk cheese can be identified as a novel class of potential PL inhibitors.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Superparamagnetic Iron Oxide Nanoparticles as a Tracer for Sentinel Lymph Node Mapping in Endometrial Cancer.","authors":"Marcin A Jedryka, Piotr Klimczak, Marcin Kryszpin, Tymoteusz Poprawski, Andrzej Czekanski, Piotr Lepka, Rafał Matkowski","doi":"10.3390/ijms26020781","DOIUrl":"10.3390/ijms26020781","url":null,"abstract":"<p><p>Sentinel lymph node (SLN) detection has been widely investigated in recent years as a part of the surgical staging of women with endometrial cancer (EC), gradually overtaking lymphadenectomy (LND) in this respect. In this study, thirty EC patients, assumed as stage I, were investigated using superparamagnetic iron oxide (SPIO) as a tracer for SLN detection followed by LND. The endpoints of this research were the proportion of successful SLN detection, the average number of SLNs per patient, the percentage of bilaterally detected SLNs, and the proportion of metastatic SLNs. Safety endpoints were the summary of all reported adverse events. SLNs were detected in all cases and bilaterally in 21 patients (70%). The diagnostic accuracy parameters of the SPIO detection of metastatic SLNs evaluated by Receiver Operating Characteristic (ROC) curve analysis with the area under the ROC curve (AUC) demonstrated a sensitivity of 80% and AUC of 0.9 (<i>p</i> < 0.001), confirming the SPIO technique's efficacy in women with EC. No adverse events were reported. SPIO nanoparticles as a tracer for SLN mapping in apparent early-stage EC patients demonstrated satisfactory accuracy parameters and safety; however, these data need to be evaluated by further research.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Senescent Cluster in Aged Human Hematopoietic Stem Cell Compartment as Target for Senotherapy.","authors":"Laura Poisa-Beiro, Jonathan J M Landry, Bowen Yan, Michael Kardorff, Volker Eckstein, Laura Villacorta, Peter H Krammer, Judith Zaugg, Anne-Claude Gavin, Vladimir Benes, Daohong Zhou, Simon Raffel, Anthony D Ho","doi":"10.3390/ijms26020787","DOIUrl":"10.3390/ijms26020787","url":null,"abstract":"<p><p>To identify the differences between aged and young human hematopoiesis, we performed a direct comparison of aged and young human hematopoietic stem and progenitor cells (HSPCs). Alterations in transcriptome profiles upon aging between humans and mice were then compared. Human specimens consist of CD34+ cells from bone marrow, and mouse specimens of hematopoietic stem cells (HSCs; Lin- Kit+ Sca1+ CD150+). Single-cell transcriptomic studies, functional clustering, and developmental trajectory analyses were performed. A significant increase in multipotent progenitor 2A (MPP2A) cluster is found in the early HSC trajectory in old human subjects. This cluster is enriched in senescence signatures (increased telomere attrition, DNA damage, activation of P53 pathway). In mouse models, the accumulation of an analogous subset was confirmed in the aged LT-HSC population. Elimination of this subset has been shown to rejuvenate hematopoiesis in mice. A significant activation of the P53-P21WAF1/CIP1 pathway was found in the MPP2A population in humans. In contrast, the senescent HSCs in mice are characterized by activation of the p16Ink4a pathway. Aging in the human HSC compartment is mainly caused by the clonal evolution and accumulation of a senescent cell cluster. A population with a similar senescence signature in the aged LT-HSCs was confirmed in the murine aging model. Clearance of this senescent population with senotherapy in humans is feasible and potentially beneficial.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered Expression of Epigenetic and Transcriptional Regulators in ERβ Knockout Rat Ovaries During Postnatal Development.","authors":"Kevin Vo, Yashica Sharma, V Praveen Chakravarthi, Ryan Mohamadi, Elizabeth S Bahadursingh, Amelia Mohamadi, Vinesh Dahiya, Cinthia Y Rosales, Grace J Pei, Patrick E Fields, M A Karim Rumi","doi":"10.3390/ijms26020760","DOIUrl":"10.3390/ijms26020760","url":null,"abstract":"<p><p>We analyzed the transcriptome data of wildtype and estrogen receptor β knockout (<i>Erβ^KO</i>) rat ovaries during the early postnatal period and detected remarkable changes in epigenetic regulators and transcription factors. Compared with postnatal day (PD) 4.5 ovaries, PD 6.5 wildtype ovaries possessed 581 differentially expressed downstream transcripts (DEDTs), including 17 differentially expressed epigenetic regulators (DEERs) and 23 differentially expressed transcription factors (DETFs). Subsequently, compared with PD 6.5 ovaries, PD 8.5 wildtype ovaries showed 920 DEDTs, including 24 DEERs and 68 DETFs. The DEDTs, DEERs, and DETFs in wildtype ovaries represented the gene expression during primordial follicle activation and the gradual development of primary follicles of first-wave origin because the second-wave follicles remained dormant during this developmental period. When we compared the transcriptome data of age-matched <i>Erβ^KO</i> ovaries, we observed that PD 6.5 <i>Erβ^KO</i> ovaries had 744 DEDTs compared with PD 4.5 ovaries, including 46 DEERs and 55 DETFs. The loss of ERβ rapidly activated the primordial follicles of both first- and second-wave origin on PD 6.5 and showed a remarkable increase in DEDTs (744 vs. 581). However, compared with PD 6.5 ovaries, PD 8.5 <i>Erβ^KO</i> ovaries showed only 191 DEDTs, including 8 DEERs and 10 DETFs. This finding suggests that the PD 8.5 <i>Erβ^KO</i> ovaries did not undergo remarkable ovarian follicle activation greater than that had already occurred in PD 6.5 <i>Erβ^KO</i> ovaries. The results also showed that the numbers of DEERs and DETFs were associated with increased changes in DEDTs; the greater the number of DEERs or DETFs, the larger the number of DEDTs. In addition to the quantitative differences in DEERs and DETFs between the wildtype and <i>Erβ^KO</i> ovaries, the differentially expressed regulators showed distinct patterns. We identified that 17 transcripts were tied to follicle assembly, 6 to follicle activation, and 12 to steroidogenesis. Our observations indicate that a loss of ERβ dysregulates the epigenetic regulators and transcription factors in <i>Erβ^KO</i> ovaries, which disrupts the downstream genes in ovarian follicles and increases follicle activation. Further studies are required to clarify if ERβ directly or indirectly regulates DEDTs, including DEERs and DETFs, during the neonatal development of rat ovarian follicles.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11765817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the Transcriptome Provides Insights into the Photosynthate of Maize Response to Salt Stress by 5-Aminolevulinic Acid.","authors":"Ying Jiang, Min Li, Yumei Qian, Hao Rong, Tao Xie, Shanshan Wang, Hong Zhao, Liangli Yang, Qingyun Wang, Yanyong Cao","doi":"10.3390/ijms26020786","DOIUrl":"10.3390/ijms26020786","url":null,"abstract":"<p><p>Salt stress is a significant environmental factor that impedes maize growth and yield. Exogenous 5-aminolevulinic acid (ALA) has been shown to mitigate the detrimental effects of various environmental stresses on plants. However, its regulatory role in the photosynthesis mechanisms of maize seedlings under salt stress remains poorly understood. Transcriptome sequencing and physiological index measurements were conducted on the leaves of the \"Zhengdan 958\" cultivar subjected to three different treatments. Differential expression analysis revealed 4634 differentially expressed genes (DEGs), including key transcription factor (TF) families such as NAC, MYB, WRKY, and MYB-related, across two comparisons (SS_vs_CK and ALA_SS_vs_SS). Significant enrichment was observed in the metabolic pathways related to porphyrin metabolism, photosynthesis-antenna proteins, photosynthesis, and carbon fixation in photosynthetic organisms. ALA treatment modulated the expression of photosynthesis-related genes, increased photosynthetic pigment content, and enhanced the activities of superoxide dismutase (SOD) and catalase (CAT), thereby mitigating the excessive accumulation of reactive oxygen species (ROS). Furthermore, ALA increased starch content under salt stress. These findings establish a foundational understanding of the molecular mechanisms through which ALA regulates photosynthesis under salt stress in maize seedlings. Collectively, exogenous ALA enhances maize's salt tolerance by regulating photosynthesis-related pathways.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11765576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA Expression Profile in Acute Ischemic Stroke.","authors":"Shraddha Mainali, Gaurav Nepal, Kirill Shumilov, Amy Webb, Paolo Fadda, Darya Mirebrahimi, Mohammad Hamed, Patrick Nana-Sinkam, Bradford B Worrall, Daniel Woo, Nicholas Johnson","doi":"10.3390/ijms26020747","DOIUrl":"10.3390/ijms26020747","url":null,"abstract":"<p><p>Acute ischemic stroke with large vessel occlusion (LVO) continues to present a considerable challenge to global health, marked by substantial morbidity and mortality rates. Although definitive diagnostic markers exist in the form of neuroimaging, their expense, limited availability, and potential for diagnostic delay can often result in missed opportunities for life-saving interventions. Despite several past attempts, research efforts to date have been fraught with challenges likely due to multiple factors, such as the inclusion of diverse stroke types, variable onset intervals, differing pathobiologies, and a range of infarct sizes, all contributing to inconsistent circulating biomarker levels. In this context, microRNAs (miRNAs) have emerged as a promising biomarker, demonstrating potential as biomarkers across various diseases, including cancer, cardiovascular conditions, and neurological disorders. These circulating miRNAs embody a wide spectrum of pathophysiological processes, encompassing cell death, inflammation, angiogenesis, neuroprotection, brain plasticity, and blood-brain barrier integrity. This pilot study explores the utility of circulating exosome-enriched extracellular vesicle (EV) miRNAs as potential biomarkers for anterior circulation LVO (acLVO) stroke. In our longitudinal prospective cohort study, we collected data from acLVO stroke patients at four critical time intervals post-symptom onset: 0-6 h, 6-12 h, 12-24 h, and 5-7 days. For comparative analysis, healthy individuals were included as control subjects. In this study, extracellular vesicles (EVs) were isolated from the plasma of participants, and the miRNAs within these EVs were profiled utilizing the NanoString nCounter system. Complementing this, a scoping review was conducted to examine the roles of specific miRNAs such as miR-140-5p, miR-210-3p, and miR-7-5p in acute ischemic stroke (AIS). This review involved a targeted PubMed search to assess their influence on crucial pathophysiological pathways in AIS, and their potential applications in diagnosis, treatment, and prognosis. The review also included an assessment of additional miRNAs linked to stroke. Within the first 6 h of symptom onset, three specific miRNAs (miR-7-5p, miR-140-5p, and miR-210-3p) exhibited significant differential expression compared to other time points and healthy controls. These miRNAs have previously been associated with neuroprotection, cellular stress responses, and tissue damage, suggesting their potential as early markers of acute ischemic stroke. This study highlights the potential of circulating miRNAs as blood-based biomarkers for hyperacute acLVO ischemic stroke. However, further validation in a larger, risk-matched cohort is required. Additionally, investigations are needed to assess the prognostic relevance of these miRNAs by linking their expression profiles with radiological and functional outcomes.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11765720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the Efficacy of Mitochondria-Accumulating Self-Assembly Peptides in Pancreatic Cancer: An Animal Study.","authors":"Ho Joong Choi, Seongeon Jin, Junghyun Park, Dosang Lee, Hee Jeong Jeong, Ok-Hee Kim, Ja-Hyoung Ryu, Say-June Kim","doi":"10.3390/ijms26020784","DOIUrl":"10.3390/ijms26020784","url":null,"abstract":"<p><p>Although pancreatic cancer presents with one of the most unfavorable prognoses, its treatment options are very limited. Mitochondria-targeting moieties, considered a new and prominent treatment modality, are expected to demonstrate synergistic anticancer effects due to their distinct mechanism compared to conventional chemotherapeutic approaches. This study evaluated the therapeutic potential of mitochondria-accumulating self-assembly peptides, referred to as Mito-FFs, utilizing both in vitro and in vivo pancreatic cancer models. Cellular viability assays revealed a concentration-dependent decrease in the survival of MIA-PACA2 pancreatic cancer cells upon exposure to Mito-FF treatment (<i>p</i> < 0.05). Subsequent in vitro Mito-FF treatments prompted the use of several molecular analyses, including Real-time PCR, Western blot analysis, and MitoSOX staining, which collectively indicated an upsurge in apoptosis, a concurrent reduction in the antioxidant enzyme expression, and an elevation in mitochondrial ROS levels (<i>p</i> < 0.05). In a murine xenograft model of pancreatic cancer, the intravenous administration of Mito-FF yielded a notable reduction in the tumor volume. Moreover, it upregulated the expression of pro-apoptotic markers, such as cleaved PARP and c-caspase 3, while concurrently downregulating the expression of an anti-apoptotic marker, MCL-1, as evidenced by both Western blot analysis and immunohistochemical staining (<i>p</i> < 0.05). It also resulted in the reduced expression of antioxidant enzymes like HO-1, catalase, and SOD2 within excised tumor tissues, as confirmed using Western blot analysis (<i>p</i> < 0.05). Cumulatively, the findings underscore the significant anticancer efficacy of Mito-FF against pancreatic cancer cells, predominantly mediated through the induction of apoptosis, suppression of antioxidant enzyme expression, and enhancement of mitochondrial ROS levels within the tumor microenvironment.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type 2 Diabetes Induces Mitochondrial Dysfunction in Zebrafish Skeletal Muscle Leading to Diabetic Myopathy via the miR-139-5p/NAMPT Pathway.","authors":"Zhanglin Chen, Zuoqiong Zhou, Qinhua Deng, Yunyi Zou, Bihan Wang, Shuaiwang Huang, Jiaqi Tian, Lan Zheng, Xiyang Peng, Changfa Tang","doi":"10.3390/ijms26020752","DOIUrl":"10.3390/ijms26020752","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a common metabolic disease that is frequently accompanied by multiple complications, including diabetic myopathy, a muscle disorder that is mainly manifested as decreased muscle function and reduced muscle mass. Diabetic myopathy is a relatively common complication among patients with diabetes that is mainly attributed to mitochondrial dysfunction. Therefore, we investigated the mechanisms underlying diabetic myopathy development, focusing on the role of microRNAs (miRs). Zebrafish were fed a high-sugar diet for 8 weeks and immersed in a glucose solution to establish a model of T2DM. Notably, the fish exhibited impaired blood glucose homeostasis, increased lipid accumulation in the skeletal muscles, and decreased insulin levels in the skeletal muscle. Additionally, we observed various symptoms of diabetic myopathy, including a decreased cross-sectional area of skeletal muscle fibers, increased skeletal muscle fibrosis, a significant decline in exercise capacity, and a significant decrease in mitochondrial respiratory function. Mechanistically, bioinformatic analysis combined with various molecular analyses showed that the miR-139-5p/NAMPT pathway was involved in long-term high-glucose-induced mitochondrial dysfunction in the skeletal muscle, leading to diabetic myopathy. Conclusively, this study provides a basis for the development of novel strategies for the prevention and treatment of diabetic myopathy.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11765840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytosine Methylation Changes the Preferred Cis-Regulatory Configuration of Arabidopsis WUSCHEL-Related Homeobox 14.","authors":"Dingkun Jiang, Xinfeng Zhang, Lin Luo, Tian Li, Hao Chen, Nana Ma, Lufeng Fu, Peng Tian, Fei Mao, Peitao Lü, Honghong Guo, Fangjie Zhu","doi":"10.3390/ijms26020763","DOIUrl":"10.3390/ijms26020763","url":null,"abstract":"<p><p>The Arabidopsis transcription factor WUSCHEL-related homeobox 14 (AtWOX14) plays versatile roles in plant growth and development. However, its biochemical specificity of DNA binding, its genome-wide regulatory targets, and how these are affected by DNA methylation remain uncharacterized. To clarify the biochemistry underlying the regulatory function of AtWOX14, using the recently developed 5mC-incorporation strategy, this study performed SELEX and DAP-seq for AtWOX14 both in the presence and absence of cytosine methylation, systematically curated 65 motif models and identified 51,039 genomic binding sites for AtWOX14, and examined how 5mC affects DNA binding of AtWOX14 through bioinformatic analyses. Overall, 5mC represses the DNA binding of AtWOX14 monomers but facilitates the binding of its dimers, and the methylation effect on a cytosine's affinity to AtWOX14 is position-dependent. Notably, we found that the most preferred homodimeric configuration of AtWOX14 has changed from ER1 to ER0 upon methylation. This change has the potential to rewire the regulatory network downstream of AtWOX14, as suggested by the GO analyses and the strength changes in the DAP-seq peaks upon methylation. Therefore, this work comprehensively illustrates the specificity and targets of AtWOX14 and reports a previously unrecognized effect of DNA methylation on transcription factor binding.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11765556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular Signaling of Amino Acid Metabolism in Prostate Cancer.","authors":"Ping Yao, Shiqi Cao, Ziang Zhu, Yunru Wen, Yawen Guo, Wenken Liang, Jianling Xie","doi":"10.3390/ijms26020776","DOIUrl":"10.3390/ijms26020776","url":null,"abstract":"<p><p>Prostate cancer is one of the most common malignancies affecting men worldwide and a leading cause of cancer-related mortality, necessitating a deeper understanding of its underlying biochemical pathways. Similar to other cancer types, prostate cancer is also characterised by aberrantly activated metabolic pathways that support tumour development, such as amino acid metabolism, which is involved in modulating key physiological and pathological cellular processes during the progression of this disease. The metabolism of several amino acids, such as glutamine and methionine, crucial for tumorigenesis, is dysregulated and commonly discussed in prostate cancer. And the roles of some less studied amino acids, such as histidine and glycine, have also been covered in prostate cancer studies. Aberrant regulation of two major signalling pathways, mechanistic target of rapamycin (mTOR) and general amino acid control non-depressible 2 (GCN2), is a key driver of reshaping the amino acid metabolism landscape in prostate cancer. By summarising our current understanding of how amino acid metabolism is modulated in prostate cancer, here, we provide further insights into certain potential therapeutic targets for managing prostate cancer through metabolic interventions.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11765784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}