{"title":"Antibiofilm activities of lactoferricin-related Trp- and Arg-rich antimicrobial hexapeptides against pathogenic <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i> strains.","authors":"Gopal Ramamourthy, Hans J Vogel","doi":"10.1139/bcb-2024-0183","DOIUrl":"10.1139/bcb-2024-0183","url":null,"abstract":"<p><p>Recently, several antimicrobial peptides (AMPs), varying in length from 12 to 37 residues, have been shown to act as antibiofilm agents. Here, we report a study of 23 hexapeptides modeled after four different Trp- and Arg-rich AMPs, including the RRWQWR-NH<sub>2</sub> peptide, derived from bovine lactoferrin. They were tested against the pathogenic Gram-negative <i>Pseudomonas aeruginosa</i> PAO1 strain and a Gram-positive <i>Staphylococcus aureus</i> MRSA strain. Both strains were engineered to express the green fluorescent protein (GFP) protein, and fluorescence detection was used to measure the ability of the peptides to prevent biofilm formation (minimum biofilm inhibitory concentration (MBIC)) or to cause the breakdown of established biofilms (minimum biofilm eradication concentration (MBEC)). Similar antibiofilm activities were obtained with the standard crystal violet dye assay. Most Trp- and Arg-rich hexapeptides displayed a potent antibiofilm activity against the Gram-positive <i>S. aureus</i> MRSA strain. In particular, hexapeptides with 3 Arg and 3 Trp were very effective, especially when they contained the three Trp in sequence. Somewhat unexpectedly, the antimicrobial (MIC) values correlated with the MBIC and MBEC values, which has not been seen for several other AMP/antibiofilm peptides. Our results demonstrate that short Trp- and Arg-rich peptides merit further studies as antibiofilm agents that could be deployed to address part of the antimicrobial resistance problem.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-18"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"E2F8 facilitates malignant phenotypes of muscle-invasive bladder cancer via increasing MCM7 expression.","authors":"Li-Yun Liu, Liang Tian, Ling-Huan Gao, Hai-Jun Cui, Xue-Mei Li, Yue-Hong Li","doi":"10.1139/bcb-2024-0083","DOIUrl":"10.1139/bcb-2024-0083","url":null,"abstract":"<p><p>E2F transcription factor 8 (E2F8) is an important regulator of the cell cycle. In this study, we first assessed the expression of E2F8 in bladder cancer and examined its effects in the malignant phenotypes of bladder cancer cell lines. We found that E2F8 was upregulated in bladder cancer tissues, and the increased expression was positively associated with higher clinical stage. E2F8 knockdown suppressed bladder cancer cell proliferation, accompanied by the performance of G1 phase arrest and the upregulated Cyclin D1 protein expression. The migrative and invasive capability was reduced in E2F8-depleted bladder cancer cells. Cisplatin resistance is an important cause of bladder cancer relapse. E2F8 downregulation facilitated cisplatin-induced apoptosis of bladder cancer cells. MCM7 is regulated by E2F and has been shown to participate in bladder cancer. There was a positive correlation between E2F8 and MCM7 expression in bladder cancer. We confirmed that E2F8 bound to the promoter region of MCM7 and activated MCM7 transcription. MCM7 overexpression abrogated the suppressive effects of E2F8 knockdown on malignant phenotypes of bladder cancer cells. We also demonstrated that E2F8 knockdown suppressed bladder cancer progression in vivo. In conclusion, we verify that E2F8 functioned in bladder cancer, and might exert its function via MCM7.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-14"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Karanveer S Johal, Sandra A Youssef, Samira M Ibrahim, Lina A Dizon-Mapula, Isabella R Galluzzo, Gilda Stefanelli
{"title":"Srcap loss alters H2A.Z-dependent and neuronal differentiation-related gene expression in N2A cells.","authors":"Karanveer S Johal, Sandra A Youssef, Samira M Ibrahim, Lina A Dizon-Mapula, Isabella R Galluzzo, Gilda Stefanelli","doi":"10.1139/bcb-2024-0294","DOIUrl":"10.1139/bcb-2024-0294","url":null,"abstract":"<p><p>The chromatin remodeler SRCAP plays a critical role in depositing the histone variant H2A.Z, which is essential for transcriptional regulation, chromatin accessibility, and neurodevelopmental processes. Despite its known importance, the mechanisms by which SRCAP regulates H2A.Z dynamics during neuronal differentiation remain poorly understood. Here, we investigated the impact of Srcap knockdown on H2A.Z incorporation and transcriptional regulation in N2A cells. Chromatin immunoprecipitation revealed reduced H2A.Z occupancy at activity-dependent and neurodevelopmental genes upon Srcap knockdown, confirming Srcap's role in H2A.Z deposition. Interestingly, CBP recruitment and global histone H3 acetylation were unaffected by Srcap knockdown at steady-state conditions, suggesting an H2A.Z-specific function of Srcap. We also observed that retinoic acid-induced neuronal differentiation leads to dynamic changes in H2A.Z levels at developmental loci, which are disrupted in Srcap-deficient cells. Gene expression analysis revealed altered expression of neurodevelopmental genes in the absence of Srcap, correlating with reduced H2A.Z occupancy. Together, these findings demonstrate that Srcap is essential for regulating H2A.Z dynamics and gene expression during neuronal differentiation, offering new insights into its role in chromatin remodelling and its potential involvement in neurodevelopmental disorders.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-12"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Valerie S Mayorga, Rafaella Navarro, Victor D Torres Roldan, Meritxell Urtecho, Silvia Tipe, Bea Calvert, Laura A Wright, Theresa J Ochoa
{"title":"Efficacy of lactoferrin supplementation in pediatric infections: a systematic review and meta-analysis.","authors":"Valerie S Mayorga, Rafaella Navarro, Victor D Torres Roldan, Meritxell Urtecho, Silvia Tipe, Bea Calvert, Laura A Wright, Theresa J Ochoa","doi":"10.1139/bcb-2024-0181","DOIUrl":"10.1139/bcb-2024-0181","url":null,"abstract":"<p><p>Pediatric infections account for approximately one-third of all deaths in children under 5 years globally. Lactoferrin (LF) supplementation has the potential to reduce infection-related morbidity due to its antimicrobial, anti-inflammatory, and immunoregulatory properties. We conducted a systematic review and meta-analysis of oral LF supplementation randomized controlled trials in population under 18 years old. The primary outcomes were infection-associated outcomes: late onset sepsis (LOS), diarrhea, and upper respiratory infections (URIs). We also analyzed mortality among LOS studies. Of 1594 citations identified, 25 studies met eligibility criteria, including 10 studies of LOS, 14 of diarrhea, and 8 of URI. LF supplementation was associated with fewer patients with culture-proven or probable neonatal LOS compared to placebo (odds ratio (OR): 0.60; 95% confidence interval (CI): 0.42-0.86), with fewer patients with diarrhea compared to placebo in children (OR: 0.56; 95% CI: 0.41-0.75), and no significant fewer patients with URI (OR: 0.61; 95% CI: 0.27-1.40). Before LF can be used as a public health intervention, it is necessary to refine some aspects of the design of future trials. Ideally these trials should be conducted in countries with the highest burden of infections, where the potential benefit is expected to have the largest impact.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-23"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lysosomal enzyme processing and trafficking in the social amoeba <i>Dictyostelium discoideum</i>.","authors":"Sean V Condie, William D Kim, Robert J Huber","doi":"10.1139/bcb-2025-0062","DOIUrl":"10.1139/bcb-2025-0062","url":null,"abstract":"<p><p><i>Dictyostelium discoideum</i> is a single-celled protist that undergoes multicellular development in response to nutrient deprivation. For close to a century, <i>D. discoideum</i> has been used as a model system for studying conserved cellular and developmental processes such as chemotaxis, cell adhesion, and cell differentiation. In the later decades of the 20th century, intensive research efforts examined the synthesis, trafficking, and activity of lysosomal enzymes in <i>D. discoideum</i>. Subsequent work revealed that lysosomes are essential for all stages of the <i>D. discoideum</i> life cycle and the genome encodes dozens of homologs of human lysosomal enzymes, including those associated with lysosomal storage diseases. Additionally, protocols for examining the trafficking and activity of lysosomal enzymes in <i>D. discoideum</i> are well-established. Here, we provide a comprehensive up-to-date review that summarizes our current knowledge of lysosomal enzyme processing and trafficking in <i>D. discoideum</i>, with an eye towards re-establishing <i>D. discoideum</i> as a model eukaryote for studying the functions of conserved lysosomal enzymes and the pathways that regulate their trafficking.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-11"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Inés Abad, Andrea Bellés, Ana Rodríguez-Largo, Lluís Luján, Ignacio de Blas, Dimitra Graikini, Laura Grasa, Lourdes Sánchez
{"title":"Lactoferrin modulates oxidative stress and inflammatory cytokines in a murine model of dysbiosis induced by clindamycin.","authors":"Inés Abad, Andrea Bellés, Ana Rodríguez-Largo, Lluís Luján, Ignacio de Blas, Dimitra Graikini, Laura Grasa, Lourdes Sánchez","doi":"10.1139/bcb-2024-0087","DOIUrl":"10.1139/bcb-2024-0087","url":null,"abstract":"<p><p>Antibiotics, specifically clindamycin (Clin), cause intestinal dysbiosis, reducing the microbiota with anti-inflammatory properties. Furthermore, Clin can induce alterations in the immune responses and oxidative stress. Lactoferrin, among other activities, participates in the maintenance of intestinal homeostasis and reduces dysbiosis induced by antibiotic treatment. The aim of this study was to analyze the effect of native and iron-saturated bovine LF in a murine model of dysbiosis induced by Clin. Six groups of male C57BL/6 mice were treated with saline (control), Clin, native lactoferrin (nLF), iron-saturated lactoferrin (sLF), nLF/Clin, or sLF/Clin. Oxidation caused in the intestinal cells of the ileum of animals subjected to different treatments was analyzed, focusing on lipid peroxidation and protein carbonyl content. The expression of inflammatory mediators was determined by qRT-PCR. Treatment with Clin did not modify lipid peroxidation, but significantly increased protein carbonyl levels up to almost 5-fold respect to the control, an effect that was reversed by orally administering sLF to mice. Furthermore, Clin increased the expression of interleukin-6 and TNF-α by 1- and 2-fold change, respectively. This effect was reversed by treatment with nLF and sLF, decreasing the expression to basal levels. In conclusion, this study indicates that lactoferrin can prevent some of the effects of Clin on intestinal cells and their associated immune system.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-12"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Retraction: The mechanism behind BAF60c in myocardial metabolism in rats with heart failure is through the PGC1α-PPARα-mTOR signaling pathway.","authors":"","doi":"10.1139/bcb-2025-0023","DOIUrl":"10.1139/bcb-2025-0023","url":null,"abstract":"","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":"103 ","pages":"1"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katrina V Good, Ladan Kalani, John B Vincent, Juan Ausió
{"title":"Multifaceted roles of MeCP2 in cellular regulation and phase separation: implications for neurodevelopmental disorders, depression, and oxidative stress.","authors":"Katrina V Good, Ladan Kalani, John B Vincent, Juan Ausió","doi":"10.1139/bcb-2024-0237","DOIUrl":"10.1139/bcb-2024-0237","url":null,"abstract":"<p><p>Methyl CpG binding protein 2 (MeCP2) is a chromatin-associated protein that remains enigmatic despite more than 30 years of research, primarily due to the ever-growing list of its molecular functions, and, consequently, its related pathologies. Loss of function <i>MECP2</i> mutations cause the neurodevelopmental disorder Rett syndrome (RTT); in addition, dysregulation of MeCP2 expression and/ or function are involved in numerous other pathologies, but the mechanisms of MeCP2 regulation are unclear. Advancing technologies and burgeoning mechanistic theories assist our understanding of the complexity of MeCP2 but may inadvertently cloud it if not rigorously tested. Here, rather than focus on RTT, we examine relatively underexplored aspects of MeCP2, such as its dosage homeostasis at the gene and protein levels, its controversial participation in phase separation, and its overlooked role in depression and oxidative stress. All these factors may be essential to understanding the full scope of MeCP2 function in healthy and diseased states, but are relatively infrequently studied and require further criticism. The aim of this review is to discuss the esoteric facets of MeCP2 at the molecular and pathological levels and to consider to what extent they may be necessary for general MeCP2 function.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":"103 ","pages":"1-12"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Retraction: MiR-1180 promotes cardiomyocyte cell cycle re-entry after injury through the NKIRAS2-NFκB pathway.","authors":"","doi":"10.1139/bcb-2025-0052","DOIUrl":"10.1139/bcb-2025-0052","url":null,"abstract":"","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":"103 ","pages":"1"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The potential role of AhR/NR4A1 in androgen-dependent prostate cancer: focus on TCDD-induced ferroptosis.","authors":"Xiang Chen, Yuan Yao, Guotong Gong, Tianji He, Chenjun Ma, Jingsong Yu","doi":"10.1139/bcb-2024-0155","DOIUrl":"10.1139/bcb-2024-0155","url":null,"abstract":"<p><p>Prostate cancer (PCa) is a complex disease with diverse molecular alterations. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that exhibits pleiotropic roles in PCa, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent ligand for AhR. While targeting ferroptosis is an innovative PCa therapeutic strategy, the impact of AhR on this process remains unclear. This study aimed to investigate the influence of AhR on lipid peroxidation and ferroptosis. Results showed that TCDD activated AhR, as evidenced by increased CYP1A1 expression, leading to reduced cell viability. TCDD caused mitochondria shrinkage, decreased the GSH/GSSG ratio, and elevated the MDA levels and lipid peroxidation. Interestingly, AhR knockdown reversed these effects, similar to the action of ferroptosis inhibitors. Mechanistically, TCDD suppressed nuclear receptor subfamily 4 group A member 1 (NR4A1) expression, in part due to AhR activation. This suppression subsequently led to a reduction in the expression of the NR4A1 downstream target stearoyl-CoA desaturase 1 (SCD1). NR4A1 overexpression counteracted the effects of TCDD. In vivo, TCDD activated AhR, downregulated NR4A1 and SCD1 expression, induced mitochondria shrinkage, and increased the MDA and 4-hydroxynonenal (4-HNE) levels. In summary, TCDD promotes ferroptosis in androgen-dependent PCa via inhibiting the NR4A1/SCD1 axis, in part dependent on AhR activation.</p>","PeriodicalId":8775,"journal":{"name":"Biochemistry and Cell Biology","volume":" ","pages":"1-11"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}