Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Enhanced Cytotoxic Effects of Docetaxel-Loaded Solid Lipid Nanoparticles (SLN-DTX) on Gastric Adenocarcinoma In Vitro","authors":"Laís Vaz-Costa,&nbsp;Marina Arantes Radicchi,&nbsp;Caterynne Melo Kauffmann,&nbsp;Guilherme Sirimarco de Souza Silveira Tonelli,&nbsp;Igor Oliveira Santos,&nbsp;Kelly Grace Magalhães,&nbsp;Sônia Nair Báo","doi":"10.1002/jbt.70456","DOIUrl":"https://doi.org/10.1002/jbt.70456","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Gastric cancer is one of the leading causes of mortality worldwide. Despite recent advances in cancer therapy, there has been little change in cure and survival rates in patients suffering from gastric cancer. The use of conventional chemotherapeutic agents such as docetaxel is limited by some disadvantages such as alopecia and hematotoxicity. This study focused on the antitumor effects of solid lipid nanoparticles loaded with docetaxel (SLN-DTX) on gastric adenocarcinoma cells. SLN-DTX showed cytotoxicity against cancer cells (AGS), demonstrating an IC50 value lower than the concentration of free DTX after 24 h of treatment, evidencing the efficiency of nanoparticles. Morphological analysis revealed structural alterations, including cell rounding and reduced cytoplasmic projections posttreatment. SLN-DTX and DTX induced damage to microtubules, binding proteins, and core fragmentation, impairing cell adhesion and proliferation. They also showed changes in analyses involving cellular organelles (mitochondria and lysosomes) and cellular metabolism. SLN-BLANK did not show significant toxicity in the AGS tumor lineage in any assays, behaving similarly to the untreated control. Association of docetaxel with solid lipid nanoparticles (SLN-DTX) demonstrates significant efficiency in inducing cytotoxic effects in gastric adenocarcinoma cells, since this formulation exhibited potent antitumor activity. Treatment with nanostructured docetaxel caused morphological and metabolic changes in addition to altering the release of molecules relevant to tumor progression. These findings support the potential use of SLN-DTX as a promising drug delivery system, offering an innovative and effective approach for gastric cancer treatment while potentially reducing the side effects associated with conventional therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70456","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Crosstalk Between Protective and Detrimental Interleukin (IL)-1 Family of Cytokines in Alzheimer's Disease","authors":"Tingting Liu,&nbsp;Xiaoyu Li","doi":"10.1002/jbt.70460","DOIUrl":"https://doi.org/10.1002/jbt.70460","url":null,"abstract":"<div>\u0000 \u0000 <p>Alzheimer's disease (AD) is a long-term, progressive, degenerative disorder. One of the most important pathological characteristics of AD is the deposition of β-amyliod (Aβ) peptide, which initiates a spectrum of cerebral neuroinflammation. Vascular changes also play an important role in the pathophysiology of the disease. Cytokines, secreted by immune cells, can facilitate cell-to-cell signaling and influence the functions of the central nervous system (CNS). These important mediators of the immune system, which are known to orchestrate various molecular and cellular mechanisms in both physiological and pathological situations, can be upregulated or downregulated, leading to a complex crosstalk with numerous receptors mediating pro-inflammatory and/or anti-inflammatory actions. In particular, the interleukin (IL)-1 family of cytokines has been implicated to significantly correlate with AD pathogenesis among other cytokines in the CNS. The IL-1 family of cytokines is essential in both the innate and adaptive immune responses. This pleiotropic family of cytokines includes IL-1α, IL-1β, IL-1 receptor antagonist (RA), IL-18, IL-33, IL-36α, IL-36β, IL-36γ, IL-36RA, IL-37, and IL-38. Recent studies have demonstrated that the upregulation of pro-inflammatory cytokines, such as IL-1α and IL-1β, or the downregulation of anti-inflammatory mediators, exerts multifaceted influences on both neurodegeneration and neuroprotection. The lack of effective treatment for AD necessitates the search for new drugs that target several processes in the disease's pathology. This review aims to give a comprehensive overview of the emerging roles of the IL-1 family of cytokines in AD pathology and to explain their perspectives on introducing novel strategies for effective therapeutic/neuropsychiatric management of AD in clinical settings by discussing both the pathogenic and protective roles of these cytokines.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective ERα Attenuates Hypothalamic ER Stress and Regulates Energy Homeostasis in Ovariectomized Mice Fed With High-Fat Diet","authors":"Amr Ali Mohamed Abdelgawwad El-Sehrawy,&nbsp; Amirhosseinjaberi,&nbsp;Ehsan Zandi,&nbsp;Farzaneh Yazdi,&nbsp;Setarehsadat Rafiei,&nbsp;Ibrokhim Sapaev,&nbsp;Sepideh KarkonShayan,&nbsp;Payam Ali Khiavi,&nbsp;Pouria Salajegheh,&nbsp;Melina Shadi,&nbsp;Reza Akhavan-Sigari","doi":"10.1002/jbt.70446","DOIUrl":"https://doi.org/10.1002/jbt.70446","url":null,"abstract":"<div>\u0000 \u0000 <p>Obesity is often caused by an imbalance between energy intake and expenditure, with the hypothalamus essential in maintaining this balance, and any impairment in its function can contribute to obesity. Estrogen receptor alpha (ERα) plays a significant role in controlling body weight by influencing energy intake. However, the specific processes through which ERα exerts its anorexigenic effects remain insufficiently understood. This study investigates the impact of targeted ERα activation on endoplasmic reticulum (ER) stress in the hypothalamus of mice suffering from obesity induced by a high-fat diet (HFD). The animals were divided into two primary groups: ovarian-intact (Sham) and ovariectomized (OVX) mice, both of which were fed an HFD for 12 weeks. At the end, the OVX mice were further divided into two groups: OVX-HFD and OVX-HFD-PPT (ERα agonist). The findings showed that ovariectomy led to weight gain and increased energy intake in HFD mice, which were accompanied by increased levels of orexigenic neuropeptide Y (NPY) and ER-stress and decreased levels of anorexigenic α-melanocyte-stimulating hormone (α-MSH) and leptin signaling in the hypothalamus. In contrast, treatment with PPT significantly attenuated these effects, leading to reduced body weight and energy intake. Mechanistically, PPT treatment decreased the level of NPY and increased α-MSH in the hypothalamus. Furthermore, PPT treatment reduced hypothalamic ER stress markers, such as GRP78 and ATF6, and enhanced leptin signaling by increasing the phosphorylation of JAK2 and STAT3. We conclude that ERα activation may reduce hypothalamic ER stress and improve leptin sensitivity, thereby regulating energy intake and body weight.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynorphin A Impairs Mitochondrial Biogenesis in Osteosarcoma Cells by Increasing SP-1","authors":"Yaxiong Dai,&nbsp;Jian Zhang,&nbsp;Yingzhen Peng,&nbsp;Lingyan Hu","doi":"10.1002/jbt.70451","DOIUrl":"https://doi.org/10.1002/jbt.70451","url":null,"abstract":"<div>\u0000 \u0000 <p>Mitochondria are vital for energy generation, apoptosis control, and cellular metabolism. As a result, they represent an attractive therapeutic target in cancer treatment, particularly osteosarcoma (OS). Despite evidence indicating that Dynorphin A exhibits anti—tumor characteristics via multiple mechanisms, its influence on the physiology of osteosarcoma (OS) has not been thoroughly investigated. In this study, we explore the impacts of Dynorphin A on mitochondrial function and biogenesis within human OS U2OS cells. Human osteosarcoma (U2OS) cells were treated with Dynorphin A at varying concentrations for 48 h. Cell viability and cytotoxicity were assessed using the Cell Counting Kit-8 (CCK-8) and LDH assay, respectively. Mitochondrial function was evaluated by measuring complex IV activity, oxygen consumption rate (OCR), and ATP production, while mitochondrial biogenesis was analyzed by determining the mtDNA/nDNA ratio, mitochondrial protein expression (NDUFB8 and MTCO₂), and mitochondrial mass (MitoTracker Red staining). The expression of key mitochondrial regulators (PGC-1α, Nrf1, TFAM) and SP-1 was quantified using real-time RT-PCR and Western blot analysis. Our findings reveal that Dynorphin A notably decreases cell viability and enhances the release of lactate dehydrogenase (LDH)., indicating cytotoxicity. It also impaired mitochondrial function, as evidenced by a decrease in complex IV activity, oxygen consumption, and ATP production. Additionally, Dynorphin A suppressed mitochondrial biogenesis, shown by a reduced mtDNA/nDNA ratio, lower expression of mitochondrial proteins (NDUFB8 and MTCO2), and decreased mitochondrial mass. Furthermore, Dynorphin A downregulated key mitochondrial regulators, including PGC-1α, Nrf1, and TFAM. Notably, Dynorphin A also upregulated SP-1 expression, and silencing SP-1 reversed its effects on mitochondrial function and biogenesis. These findings suggest that Dynorphin A exerts antitumor effects by disrupting mitochondrial function and biogenesis in OS cells.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of C57BL/6 Sub-Strain on the Innate Immune Response and Liver Recovery Following Acetaminophen-Induced Liver Injury","authors":"Giselle Sanchez-Guerrero,&nbsp;Diego K. Chavez,&nbsp;Hartmut Jaeschke,&nbsp;Anup Ramachandran","doi":"10.1002/jbt.70448","DOIUrl":"https://doi.org/10.1002/jbt.70448","url":null,"abstract":"<div>\u0000 \u0000 <p>Acetaminophen (APAP) overdose is a leading cause of acute liver failure, and the inadequacy of the current antidote N-acetylcysteine motivates the search for newer therapeutic interventions. This is facilitated by the replication of human pathophysiology by the mouse model, with the C57BL/6 strain being most used. While variations in susceptibility to liver injury between the C57BL/6(J) and (N) substrains are well recognized, substrain influence on the innate immune response and regenerative outcomes which influence development of acute liver failure are unknown. We compared these aspects temporally between 6J and 6N mice following a 300 mg/kg APAP overdose. Consistent with prior findings, 6N mice exhibited higher liver injury compared to 6J mice. Neutrophil and macrophage infiltration followed similar patterns, but with different temporal dynamics, with 6J mice showing a rapid but transient response, while 6N mice exhibited delayed and prolonged immune activity. Importantly, these immune dynamics were accompanied by delayed regeneration and sustained p21 expression, indicating impaired regeneration in 6N mice. Taken together, both substrains displayed broadly similar immune behavior in terms of cytokine expression and cell recruitment patterns, with the delayed immune resolution and regeneration observed in 6N mice being reflective of the extent of injury rather than intrinsic differences in immune function. Thus, our study emphasizes the need to evaluate multiple time points to fully capture the evolving nature of liver injury and recovery during APAP hepatotoxicity. It also underscores the importance of clearly considering and reporting mouse substrain and vendor, as these factors can significantly shape experimental outcomes and may explain discrepancies between studies using this clinically relevant model.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circ_Slc7a11 Aggravates Intestinal Mucosa Barrier Damage by Regulating SIRT1 Acetylation Through miR-624-5p","authors":"Wenqiang Yuan,&nbsp;Fang Yan,&nbsp;Shimin Wu,&nbsp;Yunhan Yang,&nbsp;Pengshuang Shi,&nbsp;Liuchan Yang,&nbsp;Dejun Cui","doi":"10.1002/jbt.70418","DOIUrl":"https://doi.org/10.1002/jbt.70418","url":null,"abstract":"<div>\u0000 \u0000 <p>SIRT1 plays a crucial role in the production of reactive oxygen species (ROS) and ischemia/reperfusion (I/R), yet the upstream mechanisms that directly regulate SIRT1 expression during intestinal I/R remain unclear. Recent studies have shown that noncoding RNAs, such as circular RNAs (circRNAs), are important players in physiological and pathological processes based on their multiple regulatory roles in gene expression. This study aimed to elucidate the role of SIRT1 in intestinal mucosa barrier damage and to investigate the regulation of SIRT1 by circRNA sponges. Third-degree burn mouse model was used. Before third-degree burn, mice were injected with miR-624-5pagomir or Circ_Slc7a11 siRNA intravenously. In addition, hypoxia reoxidation (H/R) was performed in vitro on Caco-2 cells to mimic an in vivo model of intestinal mucosa barrier damage. In vitro, SIRT1 deficiency significantly reduced H/R-induced ROS overproduction and acetylation levels by decreasing mitochondrial superoxide anion (O²⁻) levels, inhibiting NADPH oxidase activity, and enhancing antioxidant enzyme expression. miR-624-5p was pinpointed as a direct regulator of SIRT1 expression. The circRNA transcribed from the Slc7a11 gene, called Circ_Slc7a11, regulated SIRT1 expression as a sponge of miR-624-5p. Circ_Slc7a11 silencing or miR-624-5p overexpression downregulated SIRT1 expression, and reduced oxidative stress and acetylation levels to alleviate intestinal mucosa barrier damage. Elevated Circ_Slc7a11 and decreased miR-624-5p levels were observed in mice with intestinal I/R. Our results reveal the key role of Circ_Slc7a11/miR-624-5p/SIRT1 signaling pathway in regulating oxidative stress and acetylation in intestinal mucosa barrier damage.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, Biological Evaluation and Molecular Docking of Novel Sulfonamide Derivatives as Dual Inhibitors of Carbonic Anhydrase Isoenzymes I/II and Acetylcholinesterase","authors":"Sevgili Mammadova,&nbsp;Yeliz Demir,&nbsp;Zubeyda Israfilova,&nbsp;Lala Zeynalova,&nbsp;Nazar Nazarov,&nbsp;Afsun Sujayev,&nbsp;Nina Ladokhina,&nbsp;Dušan Dimić,&nbsp;Ilhami Gülçin","doi":"10.1002/jbt.70452","DOIUrl":"https://doi.org/10.1002/jbt.70452","url":null,"abstract":"<div>\u0000 \u0000 <p>In this study, a novel series of multifunctional sulfonamide-based compounds (<b>1–9</b>) incorporating aziridine, dithiocarbamate, thiocyanate, and benzo[d]thiazole fragments were synthesized through nucleophilic substitution reactions using N-2,3-dichloropropylbenzenesulfonamide as the key intermediate. The chemical structures of the synthesized compounds were elucidated by spectroscopic techniques including ¹H NMR, ¹³C NMR, and elemental analysis. The inhibitory potentials of the synthesized compounds were assessed against three key enzymes: human carbonic anhydrase isoforms I and II (hCA I and hCA II) and acetylcholinesterase (AChE). Among the synthesized derivatives, compound <b>3</b> demonstrated the highest inhibitory effect against hCA I with an K_i of 49.45 ±  9.13 nM, exhibiting approximately 4.8-fold stronger inhibition than acetazolamide (AZA). Similarly, compound <b>9</b> was the most potent inhibitor of hCA II (K_i: 36.77 ±  8.21 nM), being 5.1-fold more effective than AZA. In the AChE inhibition assay, both compounds <b>3</b> and <b>2</b> showed superior activity over the reference drug tacrine (TAC), with K_i values of 148.67  ±  78.78 nM and 151.21  ±  11.78 nM, respectively, corresponding to 2.17-fold and 2.13-fold greater potency than TAC. The molecular docking studies were performed to examine the interactions between most potent compounds and proteins. These results emphasize the importance of present structural motifs for the various interactions. These findings support the rational design of multifunctional sulfonamides as promising scaffolds for the development of potent enzyme inhibitors targeting both CA and AChE-related pathologies.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Common Food Additives Inhibit Carbonic Anhydrase Activity","authors":"Ayça Aktaş Karaçelik,&nbsp;Murat Küçük,&nbsp;Semra Alkan Türkuçar,&nbsp;Şükrü Beydemir","doi":"10.1002/jbt.70444","DOIUrl":"https://doi.org/10.1002/jbt.70444","url":null,"abstract":"<p>Few studies about the effects of food additives on human enzymes exist. The effects of 20 food additives (12 colorants, 2 antioxidants, 3 sweeteners, 2 preservatives, and 1 acidity regulator) on bovine carbonic anhydrase (bCA) and especially human isoenzymes hCAI and hCAII isoenzyme, a highly vital enzyme, were studied for the first time. All the additives showed inhibition on human CA isoenzymes with IC₅₀ values in 5-5998 μM range. The higher inhibitions were detected in the colorants, Erythrosine B showing the highest inhibition (IC_50(bCA): 11 μM, IC_50(hCAI): 19 μM and IC_50(hCAII): 5 μM) at levels comparable with standard CA inhibitor sulfanilamide, while sweeteners showed low inhibition. BHT, a synthetic antioxidant, had higher inhibition compared to ascorbic acid. According to ADMET results, when the pharmacokinetic properties of the additives are considered, the only molecule with high gastrointestinal absorption is curcumin. The findings suggest that the health concerns caused by excessive consumption of foods containing additives may be related to CA inhibition. Food additive alternatives with no/lower CA inhibition should be sought for. Besides, Erythrosine B derivatives deserve investigation for new CA inhibitors.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70444","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ROCK-Mediated Actin Remodeling Contributes to the Reduced Proliferation and Migration of bEnd.3 Endothelial Cells Treated With Florfenicol","authors":"Dongfang Hu,&nbsp;Zihui Shen,&nbsp;Xueke Hou,&nbsp;Zhishuai Wan,&nbsp;Xiaoyu Guo,&nbsp;Lingli Chen,&nbsp;Zhihong Yin,&nbsp;Hongmei Ning,&nbsp;Yaming Ge","doi":"10.1002/jbt.70453","DOIUrl":"https://doi.org/10.1002/jbt.70453","url":null,"abstract":"<div>\u0000 \u0000 <p>Florfenicol (FLO), a widely used antibiotic, can cause early embryonic death and impaired angiogenesis. However, the mechanism by which FLO inhibits angiogenesis and its role in FLO-induced embryonic toxicity are not yet fully understood. This study aimed to investigate the effect of FLO on the proliferation and migration of mouse bEnd.3 endothelial cells (bECs) and the underlying mechanism, given the crucial role of endothelial cells in angiogenesis. The results showed that FLO treatment at 7.5–15 μg/mL significantly inhibited proliferation and migration in a time-dependent manner, with stronger effects observed after 48 h compared to 24 h. RNA sequencing analysis identified 1351 genes differentially expressed in response to FLO. Functional analysis indicated that FLO disrupted ATP metabolism, angiogenesis, vasculature development, and actin filament organization. The F-actin cytoskeleton remodeling was morphologically confirmed, and activation of the ROCK/Cofilin signaling pathway was detected. Subsequent experiments demonstrated that pharmacological inhibition of the pathway normalized cytoskeletal rearrangement and promoted angiogenesis, as evidenced by enhanced wound closure and increased cell viability. Our results demonstrated that ROCK-mediated F-actin remodeling plays a crucial role in the FLO-induced inhibition of proliferation and migration in bECs. These findings may explain why FLO inhibited angiogenesis. However, further investigations are necessary to validate our findings in in vivo experiments.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of the Wiskott–Aldrich Syndrome Protein Family in Cancer Development, Invasion, and Metastasis","authors":"Yi Tian,&nbsp;Huiying Li,&nbsp;Dandi Li,&nbsp;Miao Jin","doi":"10.1002/jbt.70435","DOIUrl":"https://doi.org/10.1002/jbt.70435","url":null,"abstract":"<div>\u0000 \u0000 <p>Emerging evidence indicates that cancer metastasis is governed by distinct genetic mechanisms that operate independently of those regulating carcinogenesis and cancer proliferation. The Wiskott–Aldrich syndrome protein (WASP) family members significantly contribute to the regulation of actin cytoskeleton (AC) dynamics and cancer cell invasion and metastasis. Recent research has demonstrated that WASP and its homolog, the WASP family verprolin-homologous protein (WAVE), function as a master regulator and a key scaffolding protein, bringing together the various components of metastatic signaling complexes, thereby facilitating the development of solid tumors. The occurrence and progression of aggressive hematologic neoplasia can also be affected by WASP mutations. Recent research reveals that WASPs and WAVEs can act as either suppressors or enhancers of cancer malignancy, depending on the clinical or preclinical scenarios. WASPs and WAVEs' dual roles in cancer possibly originate from their diverse involvement in cell biology, which might be a novel approach to developing anticancer drugs. Therefore, this review aims to examine the role of the WASP family in cancer progression by focusing on their signaling network and molecular processes in both solid and hematological malignancies.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}