Frontiers in bioscience (Landmark edition)最新文献

{"title":"Growth Differentiation Factor 15 Inhibits Cardiac Fibrosis, Oxidative Stress, Inflammation, and Apoptosis in a Rat Model of Heart Failure with Preserved Ejection Fraction.","authors":"Xuyang Meng, Yi Li, Lingbing Meng, Chenguang Yang, ChenXi Xia, Xiang Wang, Fang Wang","doi":"10.31083/FBL26857","DOIUrl":"10.31083/FBL26857","url":null,"abstract":"<p><strong>Background: </strong>Heart failure with preserved ejection fraction (HFpEF) is a systemic syndrome primarily associated with fibrosis, oxidative stress, inflammation, and cellular apoptosis. Growth differentiation factor 15 (GDF15), a biomarker commonly used in clinical studies, exhibits protective effects on the myocardium. Therefore, the focus of the present study is to determine the mechanism by which GDF15 protects cardiac function in HFpEF.</p><p><strong>Methods: </strong>We conducted functional enrichment analysis and protein-protein interaction network analysis on genes highly expressed in HFpEF but lowly expressed in normal samples. We established an HFpEF rat model by feeding the rats with a high-fat diet and administering N-omega-nitro-l-arginine-methyl ester (L-NAME) in their drinking water and silenced GDF15 by tail vein injection of lentivirus (L3110). After 12 weeks of feeding, echocardiographic examinations were performed. Following euthanasia of the rats, blood and heart tissue samples were collected. Heart tissue sections were stained using Masson's trichrome and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining methods. Western blot (WB) analysis was employed to determine the concentrations of relevant proteins.</p><p><strong>Results: </strong>The echocardiographic results showed that compared with the HFpEF + MOCK group, the HFpEF+silencing GDF15 (siGDF15) group exhibited more severe cardiac dysfunction, with significant decreases in ejection fraction (<i>p</i> < 0.05) and E/A ratio (<i>p</i> < 0.001). WB results demonstrated that, compared with the HFpEF + MOCK group, the HFpEF+siGDF15 group exhibited increased expression of cardiac fibrosis-associated proteins, including collagen I (<i>p</i> < 0.01), collagen III (<i>p</i> < 0.01), and α-smooth muscle actin (α-SMA) (<i>p</i> < 0.01). Additionally, oxidative stress-associated biomarkers such as myeloperoxidase (MPO) (<i>p</i> < 0.01) and oxidized low-density lipoprotein (ox-LDL) (<i>p</i> < 0.01), inflammation-associated biomarkers, including interleukin-1 beta (IL-1β) (<i>p</i> < 0.01), interleukin-6 (IL-6) (<i>p</i> < 0.01), interleukin-8 (IL-8) (<i>p</i> < 0.01), and tumor necrosis factor α (TNFα) (<i>p</i> < 0.01), and apoptosis-associated biomarkers like cleaved caspase-3 (<i>p</i> < 0.01) and BCL2-associated X (BAX) (<i>p</i> < 0.01) were also upregulated in HFpEF+siGDF15 group.</p><p><strong>Conclusions: </strong>Our research indicates that GDF15 preserves cardiac function by inhibiting myocardial fibrosis, reducing myocardial cell oxidative stress, alleviating cardiac inflammation, and suppressing myocardial cell apoptosis.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 2","pages":"26857"},"PeriodicalIF":3.3,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Potential Mechanism and the Role of Antioxidants in Mitigating Oxidative Stress in Alzheimer's Disease.","authors":"Rayees Ahmad Naik, Mehak Naseer Mir, Ishfaq Ahmad Malik, Rima Bhardwaj, Fahad M Alshabrmi, Mahmoud Abdulrahman Mahmoud, Majid Alhomrani, Abdulhakeem S Alamri, Walaa F Alsanie, Ahmed Hjazi, Tanmoy Ghatak, Burkhard Poeggeler, Mahendra P Singh, Gopenath Ts, Sandeep Kumar Singh","doi":"10.31083/FBL25551","DOIUrl":"10.31083/FBL25551","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most prevalent cause of dementia and a significant contributor to health issues and mortality among older individuals. This condition involves a progressive deterioration in cognitive function and the onset of dementia. Recent advancements suggest that the development of AD is more intricate than its underlying brain abnormalities alone. In addition, Alzheimer's disease, metabolic syndrome, and oxidative stress are all intricately linked to one another. Increased concentrations of circulating lipids and disturbances in glucose homeostasis contribute to the intensification of lipid oxidation, leading to a gradual depletion of the body's antioxidant defenses. This heightened oxidative metabolism adversely impacts cell integrity, resulting in neuronal damage. Pathways commonly acknowledged as contributors to AD pathogenesis include alterations in synaptic plasticity, disorganization of neurons, and cell death. Abnormal metabolism of some membrane proteins is thought to cause the creation of amyloid (Aβ) oligomers, which are extremely hazardous to neurotransmission pathways, especially those involving acetylcholine. The interaction between Aβ oligomers and these neurotransmitter systems is thought to induce cellular dysfunction, an imbalance in neurotransmitter signaling, and, ultimately, the manifestation of neurological symptoms. Antioxidants have a significant impact on human health since they may improve the aging process by combating free radicals. Neurodegenerative diseases are currently incurable; however, they may be effectively managed. An appealing alternative is the utilization of natural antioxidants, such as polyphenols, through diet or dietary supplements, which offer numerous advantages. Within this framework, we have extensively examined the importance of oxidative stress in the advancement of Alzheimer's disease, as well as the potential influence of antioxidants in mitigating its effects.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 2","pages":"25551"},"PeriodicalIF":3.3,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Pathophysiology to Treatment: The Role of Ferroptosis in PCOS.","authors":"Jie An, Qin Zhou, Xiaojing Guo, Congya Xu, XiaoFang Jia, Zhenzhen Cao, Qibin Lu","doi":"10.31083/FBL25586","DOIUrl":"10.31083/FBL25586","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a prevalent gynecological endocrine and metabolic disorder in women, with an incidence rate of 10-13%. The etiology of PCOS is multifaceted, involving genetic predisposition, environmental influences, lifestyle factors, and endocrine metabolic dysregulation. Iron, a critical mineral, not only plays a role in regulating female physiological functions and the progression of PCOS but also requires careful management to avoid deficiency. However, excess iron can trigger ferroptosis, a form of nonapoptotic cell death characterized by the accumulation of lipid peroxides. While numerous studies have explored ferroptosis in patients with PCOS and animal models, the precise mechanisms and therapeutic implications remain inadequately understood. This review seeks to elucidate the pathophysiology of PCOS and the contributory factors of ferroptosis. Additionally, we examine the diverse manifestations of ferroptosis in PCOS and evaluate its role. Furthermore, we introduce ferroptosis-related traditional Chinese medicines that may enhance the understanding of PCOS pathogenesis and aid in the development of targeted therapies for ferroptosis in PCOS.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 2","pages":"25586"},"PeriodicalIF":3.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HSPB1 Orchestrates the Inflammation-Associated Transcriptome Profile of Atherosclerosis in HUVECs.","authors":"Gang Zhao, Li Zhao, Yulin Miao, Lei Yang, Lizhen Huang, Zhipeng Hu","doi":"10.31083/FBL36306","DOIUrl":"10.31083/FBL36306","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis (AS), with a profound inflammatory response, is the basis of cardiovascular diseases. Previous reports showed that heat shock protein family B member 1 (HSPB1) has a protective effect against AS, but the specific mechanism is still unclear. In this study, we aim to explore the functions and downstream targets of HSPB1 in human umbilical vein endothelial cells (HUVECs).</p><p><strong>Methods: </strong>Expression of the <i>HSPB1</i> gene was knocked down in HUVECs. Cellular phenotype was then assessed and transcriptome data (RNA-seq) was analyzed to identify the potential targets regulated by HSPB1. Moreover, RNA-seq data for human fibroatheroma (GSE104140) from the gene expression omnibus (GEO) database was re-analyzed to verify the targets of HSPB1 in AS.</p><p><strong>Results: </strong>Silencing of HSPB1 significantly reduced apoptosis (<i>p</i> < 0.0001) and increased the proliferation (<i>p</i> < 0.05) of HUVECs. The 608 differentially expressed genes (DEGs) were identified after HSPB1 knockdown, including 423 upregulated genes. DEGs, including <i>CXCL1</i>, <i>CXCL8</i>, <i>CXCL2</i>, <i>TRIB3</i>, <i>GAS5</i>, <i>SELE</i>, and <i>TNIP1</i>, were enriched in inflammatory and immune response pathways. HSPB1 was also shown to affect alternative splicing patterns of hundreds of genes, especially those enriched in apoptotic processes, including <i>ACIN1</i>, <i>IFI27</i>, <i>PAK4</i>, <i>UBE2D3</i>, and <i>FIS1</i>. An overlapping gene set was found between the HSPB1-regulated and AS-induced transcriptome. This included 171 DEGs and 250 alternatively spliced genes that were also enriched in inflammatory/immune response- and apoptosis-associated pathways, respectively.</p><p><strong>Conclusion: </strong>In summary, HSPB1 knockdown modulates the proliferation and apoptosis of HUVECs by regulating RNA levels and alternative splicing patterns. HSPB1 plays an important role in AS pathogenesis by modulating the inflammatory and immune response. This study provides novel insights for the investigation of future AS therapeutic strategies.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 2","pages":"36306"},"PeriodicalIF":3.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>RANBP1</i> Regulates <i>NOTCH3</i>-Mediated Autophagy in High Glucose-Induced Vascular Smooth Muscle Cells.","authors":"Zhong-Jiao Xu, Jian Xu, Wen-Jing Lei, Xiang Wang, Qi-Lin Zou, Lin-Chun Lv, Chong Liu, Wu-Ming Hu, Yi-Jia Xiang, Jia-Yi Shen, Tie-Min Wei, Chun-Lai Zeng","doi":"10.31083/FBL26850","DOIUrl":"10.31083/FBL26850","url":null,"abstract":"<p><strong>Background: </strong>Vascular smooth muscle cells(VSMCs) phenotypic switching under hyperglycemic conditions accelerates atherosclerotic progression. Notch receptor 3(NOTCH3), a critical stabilizer of VSMC homeostasis implicated in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) pathogenesis, ensures vascular integrity; however, its interplay with RAN Binding Protein 1(<i>RANBP1</i>) during pathological hyperglycemia remains uncharacterized. We hypothesize that hyperglycemia-induced autophagic dysregulation is mechanistically governed by theNotch receptor 3 (<i>NOTCH3</i>)/<i>RANBP1</i> axis, proliferative capacity, and apoptotic signaling in high glucose (HG)-stimulated VSMCs. The aim of this study was to elucidate the regulatory mechanisms of autophagy in VSMCs under HG conditions, with a focus on the <i>NOTCH3</i>/<i>RANBP1</i> axis and its implications for vascular health.</p><p><strong>Methods: </strong>Bioinformatics analysis was performed on <i>NOTCH3</i> sequencing data, including weighted gene co-expression network analysis (WGCNA), screening of differentially expressed genes (DEGs), and construction of a protein-protein interaction (PPI) network, to identify the key gene, RANBP1. In vitro experiments, including cell counting kit-8 (CCK-8) assays, quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting (WB), and flow cytometry, were conducted to examine the effects of <i>NOTCH3</i> knockdown combined with <i>RANBP1</i> overexpression on glucose-induced autophagy marker expression and cell viability in VSMCs.</p><p><strong>Results: </strong><i>NOTCH3</i> knockdown suppressed VSMC proliferation and induced apoptosis, and the cell cycle was stopped at the S phase. Analysis of VSMC sequencing data revealed 38 overlapping genes between the turquoise module and DEGs, 11 (<i>HPF1</i>, <i>RANBP1</i>, <i>CRNKL1</i>, <i>LGALS3</i>, <i>RDX</i>, <i>ECM1</i>, <i>CXCL5</i>, <i>PA2G4</i>, <i>CENPS</i>, <i>ZNF830</i>, and <i>HIST1H4L</i>) of which were significantly underexpressed in VSMC samples with si-<i>NOTCH3</i>. In a dose-dependent manner, HG therapy altered the expression of autophagy-related markers, upregulated <i>NOTCH3</i>, and downregulated phosphorylated mammalian target of rapamycin (p-mTOR). Downregulation of <i>NOTCH3</i> aggravated the effects of HG on cell viability and autophagy, whereas overexpression of <i>RANBP1</i> reversed these effects, suggesting an offsetting effect on HG-induced autophagy.</p><p><strong>Conclusion: </strong>On the basis of sequencing technology, bioinformatics analysis and cell experiments, we conclude that the <i>RANBP1</i>/<i>NOTCH3</i> axis is essential for the control of autophagy and survival of VSMCs under hyperglycemic stress and could provide new insight for the clinical treatment of VSMC-related diseases.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 2","pages":"26850"},"PeriodicalIF":3.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the <i>AURKB</i>-<i>MAD2L2</i> Axis Disrupts the DNA Damage Response and Glycolysis to Inhibit Colorectal Cancer Progression.","authors":"Shengjie Li, Jiayou Ye, Kaifeng Yang, Chengfan Xu, Zhixiang Qin, Yiyang Xue, Lanjian Yu, Tianyu Zhou, Ziming Yin, Bin Sun, Jun Xu","doi":"10.31083/FBL26532","DOIUrl":"10.31083/FBL26532","url":null,"abstract":"<p><strong>Background: </strong>Dysregulated metabolic pathways, including glycolysis and a compromised DNA damage response (DDR), are linked to the progression of colorectal cancer (CRC). The mitotic arrest deficient-like 2 (<i>MAD2L2</i>) and aurora kinase B (<i>AURKB</i>) genes play roles in cell cycle regulation and the DDR, making them potential targets for CRC therapy.</p><p><strong>Methods: </strong>Differential expression analysis was performed using The Cancer Genome Atlas-Colon Adenocarcinoma (TCGA-COAD) and GSE47074 datasets. A predictive model was established, and gene expression levels were further analyzed. The Gene Expression Profiling Interaction Analysis database and co-immunoprecipitation experiments assessed the correlation between AURKB and MAD2L2. Knockdown experiments in CRC cell lines further investigated the role of <i>AURKB</i>, followed by analyses of cell behavior, oxidative stress, glycolysis, DDR, and interaction with <i>MAD2L2</i>.</p><p><strong>Results: </strong>The risk model identified six prognostic genes (BUB1 mitotic checkpoint serine/threonine kinase B (<i>BUB1B</i>), <i>AURKB</i>, aurora kinase A (<i>AURKA</i>), exonuclease 1 (<i>EXO1</i>), topoisomerase II alpha (<i>TOP2A</i>), cyclin A2 (<i>CCNA2</i>)) associated with CRC, which were significantly expressed in tumor samples from the TCGA-COAD and GSE47074 datasets. <i>In vitro</i> assays confirmed that <i>AURKB</i> knockdown inhibited CRC cell behavior, induced G1 cell cycle arrest, and increased oxidative stress and apoptosis. <i>AURKB</i> knockdown also impaired glycolysis, reducing lactate production, glucose uptake, and ATP levels. Overexpression of <i>MAD2L2</i> partially reversed these effects, restored glycolytic activity, and mitigated the cell cycle arrest and DDR caused by <i>AURKB</i> knockdown.</p><p><strong>Conclusion: </strong><i>AURKB</i> regulates CRC progression by modulating glycolysis and DDR pathways. Targeting the <i>AURKB</i>-<i>MAD2L2</i> axis offers a promising therapeutic strategy for disrupting fundamental metabolic and DNA repair mechanisms in CRC.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 2","pages":"26532"},"PeriodicalIF":3.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polarized Tissue-Derived Macrophages Display Enhanced M2d Phenotype after Prolonged Stimulation with Adenosine A_2A Receptor Agonist in the Presence of LPS.","authors":"Julia Barilo, Mariane Ratsimor, Agnes Chan, Hannah Hembruff, Sam Basta","doi":"10.31083/FBL27638","DOIUrl":"10.31083/FBL27638","url":null,"abstract":"<p><strong>Background: </strong>Macrophages (Mφ) are innate immune cells known for their different activation phenotypes, classically described as falling within two broad categories, M1 and M2. The latter were originally described as alternatively activated M2 cells to differentiate them from classically activated M1 cells. M2 cells were later classified into M2a (interleukin (IL)-4), M2b (immune complex), M2c (IL-10) and M2d (5-(N-ethylcarboxamido) adenosine (NECA) + lipopolysaccharide (LPS)) based on their inducing stimuli. Considering the established role of M2d/tumour-associated macrophage (TAM) cells within cancer initiation and proliferation, expanding on the knowledge of M2d characteristics can provide fundamental information for Mφ targeted immunotherapy. The precise characterization of M2d cells derived from tissues has not been described in detail.</p><p><strong>Methods: </strong>Our study focused on spleen-derived macrophages (SpM), which were also compared to bone marrow-derived macrophages (BMDMs).</p><p><strong>Results: </strong>By investigating different conditions for M2d-specific stimulation and employing various assays including functional tests, we show how Mφ M2d (NECA + LPS) polarization can be affected by prolonged culture conditions to induce a phenotype that was clearly different from M2a cells.</p><p><strong>Conclusion: </strong>This work offers new insights into the properties of primary M2d Mφ following extended stimulation with LPS and NECA.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 2","pages":"27638"},"PeriodicalIF":3.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncovering Sex-Related Differences in Skin Macrophage Polarization During Wound Healing in Diabetic Mice.","authors":"Coco X Huang, Elisha Siwan, Callum J Baker, Zhuoran Wei, Diana Shinko, Helen M McGuire, Stephen M Twigg, Danqing Min","doi":"10.31083/FBL27113","DOIUrl":"10.31083/FBL27113","url":null,"abstract":"<p><strong>Background: </strong>Chronic wounds, such as diabetes-related foot ulcers, arise from delayed wound healing and create significant health and economic burdens. Macrophages regulate healing by shifting between pro- and anti-inflammatory phenotypes, known as macrophage polarization. Sex and diabetes can impair wound healing, but their influence on macrophage phenotype in skin tissue during wound healing remains unclear, which was investigated in this study using a novel two-sex diabetic mouse model.</p><p><strong>Methods: </strong>Diabetes was induced in male and female C57BL/6J mice using low-dose streptozotocin injections and high-fat diet feeding, with chow-fed mice as controls. After 18 weeks, each mouse received four circular full-thickness dorsal skin wounds. The macrophage phenotypes in wounded skin tissues at Day 0 and Day 10 post-wounding were analyzed using mass cytometry with manual gating and automated computational clustering.</p><p><strong>Results: </strong>Male diabetic mice exhibited more severe hyperglycemia and insulin resistance compared to females. Although diabetic mice did not display delayed wound healing, male mice had a greater proportion of total macrophages than females, especially a higher proportion of pro-inflammatory matrix metalloproteinase-9 (MMP-9)+ macrophages and a lower proportion of anti-inflammatory adiponectin receptor 1 (AdipoR1)+ macrophages in male diabetic mice compared to females, indicating an imbalanced polarization towards a pro-inflammatory phenotype that could result in poorer wound healing. Interestingly, computational clustering identified a new pro-inflammatory, pro-healing phenotype (Ly6C+AdipoR1+CD163-CD206-) more abundant in females than males, suggesting this phenotype may play a role in the transition from the inflammatory to the proliferative stage of wound healing.</p><p><strong>Conclusions: </strong>This study demonstrated a significant sex-based difference in macrophage populations, with male diabetic mice showing a pro-inflammatory bias that may impair wound healing, while a unique pro-inflammatory, pro-healing macrophage population more abundant in females could facilitate recovery. Further research is needed to investigate the role of these newly identified phenotypes in regulating impaired wound healing.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 2","pages":"27113"},"PeriodicalIF":3.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacteria- and Phage-Derived Proteins in Phage Infection.","authors":"Olga I Guliy, Stella S Evstigneeva","doi":"10.31083/FBL24478","DOIUrl":"10.31083/FBL24478","url":null,"abstract":"<p><p>Phages have exerted severe evolutionary pressure on prokaryotes over billions of years, resulting in major rearrangements. Without every enzyme involved in the phage-bacterium interaction being examined; bacteriophages cannot be used in practical applications. Numerous studies conducted in the past few years have uncovered a huge variety of bacterial antiphage defense systems; nevertheless, the mechanisms of most of these systems are not fully understood. Understanding the interactions between bacteriophage and bacterial proteins is important for efficient host cell infection. Phage proteins involved in these bacteriophage-host interactions often arise immediately after infection. Here, we review the main groups of phage enzymes involved in the first stage of viral infection and responsible for the degradation of the bacterial membrane. These include polysaccharide depolymerases (endosialidases, endorhamnosidases, alginate lyases, and hyaluronate lyases), and peptidoglycan hydrolases (ectolysins and endolysins). Host target proteins are inhibited, activated, or functionally redirected by the phage protein. These interactions determine the phage infection of bacteria. Proteins of interest are holins, endolysins, and spanins, which are responsible for the release of progeny during the phage lytic cycle. This review describes the main bacterial and phage enzymes involved in phage infection and analyzes the therapeutic potential of bacteriophage-derived proteins.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 2","pages":"24478"},"PeriodicalIF":3.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Ferroptosis: Acteoside as a Neuroprotective Agent in Salsolinol-Induced Parkinson's Disease Models.","authors":"Hongquan Wang, Shuang Wu, Qiang Li, Huiyan Sun, Yumin Wang","doi":"10.31083/FBL26679","DOIUrl":"10.31083/FBL26679","url":null,"abstract":"<p><strong>Background: </strong>Salsolinol (SAL) is a dopamine metabolite and endogenous neurotoxin that exerts neurotoxicity to dopaminergic neurons and is involved in the genesis of Parkinson's disease (PD). However, the machinery underlying SAL-induced neurotoxicity in PD is still being elucidated.</p><p><strong>Methods: </strong>In the present study, we first used RNA-seq and KEGG analysis to examine differentially expressed genes in SAL-challenged SH-SY5Y cells. PD animal models were established and treated with acteoside. Cell viability assays, lipid peroxidation assessments (malondialdehyde [MDA] and 4-Hydroxynonenal [4-HNE]), immunoblot, and transmission electron microscopy were used to confirm acteoside-mediated inhibition of ferroptosis and its neuroprotective effect on dopaminergic (DA) neurons.</p><p><strong>Results: </strong>We found that ferroptosis-related pathway was enriched by SAL. SAL inducing ferroptosis through upregulating long-chain acyl-CoA synthetase family member 4 (ACSL4) in SH-SY5Y cells, which neurotoxic effect was reversed by ferroptosis inhibitors ferrostatin-1 (Fer-1) and deferoxamine (DFO). Acteoside, a phenylethanoid glycoside of plant origin with a neuroprotective effect, attenuates SAL-induced neurotoxicity by inhibiting ferroptosis in <i>in vitro</i> and <i>in vivo</i> PD models through downregulating ACSL4.</p><p><strong>Conclusions: </strong>The present study revealed a novel molecular mechanism underlying SAL-induced neurotoxicity via induction of ferroptosis in PD, and uncovered a new pharmacological effect against PD through inhibiting ferroptosis. This study highlights SAL-induced neurotoxicity via ferroptosis as a potential therapeutic target in PD.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 2","pages":"26679"},"PeriodicalIF":3.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}