Drug Development Research最新文献

{"title":"VG081821: A ZM241385-Like A2A Receptor Antagonist With Significant Improvement in Pharmacokinetics","authors":"Sanxing Sun,&nbsp;Chongbo Hu,&nbsp;Jinqi Ye,&nbsp;Tingting Pan,&nbsp;Yanfen Jin,&nbsp;Tan Qin,&nbsp;Zhengshu Chen,&nbsp;Long Zhao","doi":"10.1002/ddr.70133","DOIUrl":"10.1002/ddr.70133","url":null,"abstract":"<div>\u0000 \u0000 <p>ZM241385 is a potent, selective A_2A receptor antagonist/inverse agonist, and has been one of the most widely used tool compounds in studies exploring the role of A_2A receptors in various conditions or probing relevant biology. However, its rapid metabolism and poor pharmacokinetic properties hindered its therapeutic use. We addressed this limitation by modifying the 4-hydroxy group on its phenyl ring, which led to the invention of VG081821. It was hypothesized that the structural modification would allow VG081821 to interact with adenosine receptors in more or less the same way. As a result, VG081821 possesses similar binding affinities and antagonistic/inverse agonistic effects on the A_2A receptor. Crucially, it possesses significantly improved metabolic stability and pharmacokinetic properties. In-vitro and in-vivo studies demonstrated VG081821's lower intrinsic clearance and superior pharmacokinetic profile compared to ZM241385. Given that more and more studies indicate that blocking A_2A receptors has multiple beneficial effects, VG081821 may have the real potential to become a clinically valuable multi-indication therapeutic agent.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Target-Specific Potency and Drug-Ability Profile of Flavonoids Against Lung Cancer: An Integrative Multi-Omics Approach for Lead Identification","authors":"Ali M. Alaseem,&nbsp;Glowi Alasiri,&nbsp;Arockia Babu Marianesan,&nbsp;Thakur Gurjeet Singh,&nbsp;Prawez Alam,&nbsp;Mohammad Fareed,&nbsp;Nisha Bansal","doi":"10.1002/ddr.70131","DOIUrl":"10.1002/ddr.70131","url":null,"abstract":"<div>\u0000 \u0000 <p>Since lung cancer accounts for approximately 20% of cancer-related fatalities globally, it is one of the most common and deadly cancers, necessitating the discovery of innovative, potent, and less toxic treatment agents as imperative. Opportunistically, phytoflavonoids (PFs), a specific class of phytochemicals, display promising anticancer activity through their multimodal apoptosis-inducing properties. Based on existing evidence, the present study employs an integrative multi-omics approach to assess the target-specific binding efficacy and drug-ability outlines of PFs against lung cancer. We selected two of the most likely lung cancer targets using the core part of PFs: carbonic anhydrase IX (PDB ID: 3DAZ) and poly(A) binding protein cytoplasmic 1 (PDB ID: 3KUJ). Another two key targets, glutathione S-transferase P1 (PDB ID: 3GSS) and 17β-hydroxysteroid dehydrogenase 1 (HSD17B1, 3HB4), were also included in our study based on recent literature. The potency of 66 PFs against four targets was assessed through a molecular docking study using PyRx 0.8-AutoDock 4.2 software. PF15, PF43, PF6, and PF26 were the lead candidates. Further, physicochemical profiles through standard Lipinski rule of five parameters and toxicity and drug-ability profiles suggested that PF43 (naringenin) is the most ideal lead candidate among them. Molecular dynamics (MD) simulation studies were performed at 200 ns to observe the kinetic behaviors of CA9-PF43 and CA9-U-1014 docking complexes along with the calculated free energy through the MM/PBSA method. From both analyses, PF43 showed higher stability and lower free energy, expressing its potency over the standard drug. We also investigated the structure-activity relationship and frontier molecular orbitals to highlight the drug chemistry of lead PFs. The integrative multi-omics investigation suggested that using PF43 for lung cancer treatment could increase the chances of experimental success. Overall, the systematic computational analyses provide a platform for lead identification and pave the way for precision phytotherapy in current drug discovery.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Novel Neddylation-Related Molecular Subtypes in Non-Small Cell Lung Cancer With Implications for Prognosis and the Immune Landscape","authors":"Chuli Pan,&nbsp;Xiaofeng Yu","doi":"10.1002/ddr.70126","DOIUrl":"10.1002/ddr.70126","url":null,"abstract":"<div>\u0000 \u0000 <p>Lung cancer stands as the primary cause of fatalities contacted to cancer, with nonsmall cell lung cancer (NSCLC) comprising the bulk of these cases. Protein neddylation, a posttranslational alteration akin to ubiquitination. The study aims to identify neddylation-related genes in NSCLC and to predict molecular models hold significant promise for forecasting the prognosis of NSCLC patients. Clinical information stemmed from the Cancer Genome Atlas (TCGA) database; neddylation-related genes (NRGs) were obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Patients were clustered into two subtypes utilizing the Kmeans method. These genes were then screened using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression. A nomogram was created to predict the prognosis of NSCLC. The model was validated in independent Gene Expression Omnibus (GEO) data sets: GSE30219. We performed extensive model validations to assess the prognostic significance of the signature. The immune landscape of risk groups was characterized using Single Sample Gene Set Enrichment Analysis (ssGSEA), ESTIMATE and CIBERSORT algorithms. Subsequently, we also performed drug sensitivity evaluation. Based on the expression profiles of 26 neddylation-associated genes, we classified patients into two distinct subtypes, then identified ten neddylation-related genes that serve as prognostic biomarkers. Receiver operating characteristic (ROC) curves noted that these neddylation-related were effective in predicting patients prognosis. Furthermore, patients at high-risk have poor survival rates. Besides, high-risk group exhibited lower immune cell infiltration levels, displayed a marked divergence in the expression pattern of immune checkpoint molecules. Lastly, we identified potential drugs and evaluated the drug sensitivity for NSCLC. In conclusion, we constructed novel neddylation-related molecular subtypes and revealed their immunological characteristics that may function as prognostic biomarkers for NSCLC patients.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing Poloxamers as Antimicrobial Agents: A Comprehensive Review of Mechanisms and Applications","authors":"Sheila I. Peña Corona,&nbsp;Fabiola V. Borbolla-Jiménez,&nbsp;Lorena Duarte-Peña,&nbsp;Angélica Moreno,&nbsp;Luis E. Pérez-Caltzontzin,&nbsp;María Luisa Del Prado-Audelo,&nbsp;Alejandra Romero-Montero,&nbsp;Maykel González-Torres,&nbsp;Hernán Cortés,&nbsp;Hector Hernández-Parra,&nbsp;Javad Sharifi-Rad,&nbsp;Gerardo Leyva-Gómez","doi":"10.1002/ddr.70130","DOIUrl":"10.1002/ddr.70130","url":null,"abstract":"<div>\u0000 \u0000 <p>In the last decades, the misuse and overuse of antimicrobial medications have precipitated the appearance of antimicrobial resistance, a phenomenon associated with around 4.95 million deaths per year worldwide. Control of this resistance represents the biggest challenge for antimicrobial therapies and novel drug formulations. Poloxamers are nonionic synthetic triblock copolymers used as excipients for formulating antibiotics, mainly as emulsifying agents, gelling agents, surfactants, and humectants. It has been discovered that poloxamers may have antimicrobial activity as microbicides or micro biostatics or can also potentiate other germicide drugs' efficacy. This review aims to examine the use of poloxamers and synthesize their potential mechanisms of action as antimicrobial drugs for treating microbial infections. This review's methodology included sourcing articles from PubMed, Google Scholar, and Scopus, using specific medical subject headings terms to warranty precision and pertinence. Poloxamer action mechanisms include quorum sensing inhibition, cellular membrane disruption, bacterial biofilm inhibition, and disruptions in bacteria cell walls. Results of Molecular docking demonstrated that poloxamers could interact directly with active sites of adhesion proteins and alter their functioning. Our experimental tests showed that poloxamers 188 and 407 possess the potential to be antimicrobial agents by effectively inhibiting <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i> growth. Despite the convincing evidence, further research is required to overcome challenges related to poloxamers' bioavailability and establish effective dosing regimens for different poloxamers to warrant their use and safety as antimicrobial drugs.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flavoxanthin Binds to AGR2 to Mediate Fatty Acid Oxidation and Reinforce Anoikis in Lung Adenocarcinoma","authors":"Meiling Sheng,&nbsp;Qunzhi Wang,&nbsp;Yabo Lou,&nbsp;Yuanchao Xiao,&nbsp;Xiaoming Wu","doi":"10.1002/ddr.70129","DOIUrl":"10.1002/ddr.70129","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Traditional Chinese medicine (TCM) can not only alleviate symptoms in cancer patients and improve their life quality but also serve as an adjuvant therapy to reduce the toxic side effects of chemotherapy and radiotherapy, making it a hot topic in anti-tumor drug development in recent years. This project was designed to probe into the small molecular Chinese medicine components with targeted effects on lung adenocarcinoma (LUAD) and further reveal their mechanisms. Based on The Cancer Genome Atlas dataset analysis of anterior gradient-2 (AGR2) expression in LUAD, Autodock docking and scoring were employed to screen small molecular drugs that bound to AGR2. The gene set enrichment analysis was utilized to analyze enriched pathways of AGR2. By utilizing the cellular thermal shift assay, the binding relationship between Flavoxanthin and AGR2 was validated. The expression of AGR2, long-chain acyl-CoA synthetase (ACSL1), and carnitine palmitoyltransferase 1A was detected by reverse transcription-quantitative polymerase chain reaction. The cell counting kit-8 was leveraged to determine the half maximal inhibitory concentration (IC₅₀) and cell viability. Levels of fatty acid β-oxidation were measured, and BODIPY neutral lipid droplet staining was employed to evaluate fatty acid oxidation (FAO) intensity. The degree of anoikis was assessed by flow cytometry to detect apoptosis and western blot to detect anoikis-associated proteins. The immunohistochemistry was employed to measure the levels of Ki67 and Caspase-3. Tunel was applied to the detection of cell death. The result showed that flavoxanthin bound to highly-expressed AGR2 to reinforce anoikis in LUAD cells. Overexpression of AGR2 facilitated FAO inhibition of anoikis in LUAD. Flavoxanthin eliminated the promoting effect of AGR2 overexpression on FAO and restored the anoikis of LUAD cells. Animal experiments revealed that Flavoxanthin suppressed the malignant progression of LUAD through AGR2-mediated FAO. In conclusion, Flavoxanthin hinders FAO and boosts LUAD anoikis by targeting AGR2. These findings suggested that Flavoxanthin may be a novel option for intervention and treatment of LUAD, representing an instrumental advancement of small molecular components of TCM in modern oncology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beta-Lapachone: Effects on Proliferation, Survival, Migration, Cell Cycle, and lncRNA Modulation in Bladder Cancer Cells With Distinct TP53 Profiles","authors":"Tatiane Roquete Amparo,&nbsp;Kamila de Fátima da Anunciação,&nbsp;Tamires Cunha Almeida,&nbsp;Glenda Nicioli da Silva,&nbsp;Geraldo Célio Brandão","doi":"10.1002/ddr.70128","DOIUrl":"10.1002/ddr.70128","url":null,"abstract":"<div>\u0000 \u0000 <p>α-Lapachone (aLAP) and β-lapachone (bLAP) are noteworthy anticancer naphthoquinones. The chemoresistance observed in bladder cancer represents a global health concern, with relation to mutations in the <i>TP53</i> gene and alterations in the expression of long noncoding RNA (lncRNAs). This study evaluated the effects of aLAP and bLAP on bladder tumor cell lines with different <i>TP53</i> statuses: RT4 low-grade tumor with wild-type <i>TP53</i>), T24 and J82 (high-grade tumor with mutation in the <i>TP53</i> gene). Cytotoxicity was assessed using the MTT reduction method and cell migration by scratch assay, while clonogenic survival and cell cycle were evaluated through cell colony counting and flow cytometry, respectively. The expression of lncRNAs linked to bladder cancer and associated with tumor progression and prognosis (<i>JHDM1D-AS1</i>, <i>SBF2-AS1</i>, <i>CDT-2132N18.2</i>, and <i>RP11-363E7.4</i>) and the <i>JHDM1D</i> gene was evaluated through RT-qPCR. bLAP demonstrated greater cytotoxicity than aLAP. Its inhibitory effects on clonogenic survival, migration, and the cell cycle were observed in all cell lines and were related to the modulation of lncRNAs expression. A reduction in lncRNA <i>SBF2-AS1</i> and <i>JHDM1D</i> gene expression was observed in RT4 cells, accompanied by an increase in lncRNA <i>RP11-363E7.4</i>. Conversely, in the cells with mutated <i>TP53</i> (J82), a reduction in <i>JHDM1D-AS1</i> and <i>JHDM1D</i> was observed. The downregulation of <i>JHDM1D-AS1</i> and <i>SBF2-AS1</i>, along with the upregulation of <i>RP11-363E7.4</i>, may be associated with the observed inhibition of proliferation and cell migration following bLAP treatment. The antiproliferative effects of bLAP in bladder cancer cells are independent of <i>TP53</i> statuses, yet occur through a distinct action mechanism, with variations in lncRNAs expression.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Leishmanicidal Efficacy of Synthesized Arylidene Analogues of Glitazone","authors":"Janine Aucamp,&nbsp;Helena D. Janse van Rensburg,&nbsp;Simon S. Mnyakeni-Moleele,&nbsp;Keisuke Suganuma,&nbsp;David D. N'Da","doi":"10.1002/ddr.70125","DOIUrl":"10.1002/ddr.70125","url":null,"abstract":"<p>Diabetes is a fast-growing health issue in low- and middle-income countries, with ~80% of diabetics living in the tropics and sub-tropics. It is a deadly condition claiming the lives of millions of individuals annually, with no therapeutic treatment available to date. The management of diabetes is thus limited to symptomatic relief by glycemic control. Furthermore, the geographical overlap of diabetes and neglected tropical diseases (NTDs) is of concern, as diabetes is known to increase infection susceptibility and severity. In contrast, diabetes-infection comorbidity can negatively affect treatment responses. Leishmaniasis ranks among the top 10 NTDs. Its current therapeutic treatment relies on a handful of drugs that are marred with two main shortcomings: toxicity and reduced efficacy due to pathogenic resistance. Hence, there is a pressing need for new, effective antileishmanial therapeutics. There is evidence of rising cases of leishmaniasis-diabetes co-infection, which may require the use of dual-active therapeutics to curb them. In search of new effective antileishmanial agents with potential for dual use, we evaluated in vitro the antileishmanial and antidiabetic activities of a series of arylidenes derived from hydantoin, glitazone, and rhodanine scaffolds using phenotypic assays, some of which had previously been investigated for antidiabetic potential. Additionally, the antitrypanosomal potential of these compounds was also considered due to the taxonomic relation between <i>Leishmania</i> and <i>Trypanosoma</i> spp. and reported concerns of Chagas disease and human African trypanosomiasis-diabetes comorbidities. Three leishmanicidal early leads with submicromolar activity were uncovered, but no antitrypanosomal or dual leishmaniasis-diabetes active hits were identified.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.70125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced Taurine Transporter Expression in Lymphoblastoid Cell Lines From Alzheimer's Disease Patients Compared With Age-Matched Controls: Therapeutic Implications?","authors":"Yuval Gavriel,&nbsp;Irena Voinsky,&nbsp;Hana Klin,&nbsp;Alessio Squassina,&nbsp;David Gurwitz","doi":"10.1002/ddr.70124","DOIUrl":"10.1002/ddr.70124","url":null,"abstract":"<p>Taurine is an atypical amino acid that cannot form peptide bonds and thus does not take place in building proteins. Yet, taurine takes part in regulating many cell functions, including cell osmolarity and volume, mitochondrial function, membrane ion channels and neuronal activity, and cell survival. Taurine is synthesized by the liver, and available from consumption of meat and fish, but not plants. It has millimolar concentrations in the brain, skeletal muscle, blood, heart, retina, and other tissues. Taurine is transported from the liver (following synthesis) or the intestine (following consumption) to blood by the taurine transporter, encoded in humans by <i>SLC6A6</i>. A recent study reported that blood taurine declines dramatically in aged individuals. Several studies indicated that dietary taurine slows cognitive decline in Alzheimer's disease (AD) model mice. We therefore measured <i>SLC6A6</i> mRNA expression in human lymphoblastoid cell lines (LCLs) from AD patients and age-matched controls and observed 2.8-fold lower expression in AD LCLs (<i>p</i> = 0.0005). Additionally, glutathione peroxidase 1 (<i>GPX1</i>), a key free-radical scavenging selenoenzyme, had reduced mRNA expression in LCLs from AD patients compared with controls. Our observations suggest that reduced taurine transporter expression may contribute to AD pathogenesis and that dietary taurine might be beneficial for slowing disease progression in early-stage AD. Clinical trials with dietary taurine supplementation of individuals with mild cognitive impairment (MCI) or early-stage AD are required to assess its tentative therapeutic potential.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.70124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144581896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRPC1 and TRPC5 in Colorectal Cancer: Mechanisms, Prognostic Markers, and Therapeutic Targets","authors":"Manal A. Abbas,&nbsp;Aya Y. Al-Kabariti,&nbsp;Randa El-Rayyes,&nbsp;Razan Obeidat,&nbsp;Abd-Alrahman Al-Rayyes","doi":"10.1002/ddr.70123","DOIUrl":"10.1002/ddr.70123","url":null,"abstract":"<div>\u0000 \u0000 <p>Colorectal cancer (CRC) is one of the most frequent and deadliest cancers worldwide, ranking third in prevalence and second in cancer-related deaths. Treating CRC remains a major challenge due to several factors: many cases are diagnosed at advanced stages, variable response to treatment due to genetic differences in patients, chemotherapy resistance, and the adverse effects of existing therapies. This highlights the urgent need for early diagnostic markers and effective treatments with fewer side effects. Recent research has identified transient receptor potential canonical (TRPC) channels as key regulators in the development and progression of cancer, although their specific role in CRC is not yet fully characterized. This review summarizes TRPCs pathophysiological functions, signaling pathways, interactions with other calcium channels, and their potential use as diagnostic and prognostic tools in clinical practice. Special emphasis is given to TRPC1 and TRPC5, as they represent the most extensively studied members of the TRPC family. This review also discusses potential therapeutic approaches targeting them, offering valuable insights for further advances in CRC research.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AMPK/mTOR/ULK1 Pathway Participates in Autophagy Induction by Curcumin in Colorectal Adenoma Mouse Model","authors":"Yuge Wang,&nbsp;Moxixuan Liu,&nbsp;Xuemei Jia,&nbsp;Qian Yang,&nbsp;Yao Du","doi":"10.1002/ddr.70115","DOIUrl":"10.1002/ddr.70115","url":null,"abstract":"<p>Colorectal adenoma (CRA) represents a pathological condition characterized by the aberrant development of intestinal epithelial cells and alterations in cellular differentiation within the colorectal mucosal epithelium, posing an increased risk for malignant transformation if not adequately addressed. Curcumin has been shown to exhibit a range of therapeutic effects across various diseases, which motivated this investigation utilizing C57BL/6 mice as a model system. Methodologies including hematoxylin-eosin staining (HE), western blot analysis, RT-PCR, immunofluorescence, and electron microscopy were employed to evaluate proteins associated with the <i>AMPK/mTOR/ULK1</i> signaling pathway. The study specifically examined variations in key autophagy-related proteins such as <i>Beclin-1, LC3, P62</i>, alongside intestinal junction proteins <i>Occludin, ZO-1, and Claudin-1</i>. This study seeks to elucidate whether curcumin can influence autophagy-related mechanisms in intestinal mucosal epithelial cells affected by colorectal adenoma to achieve potential therapeutic outcomes.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 5","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}