Current molecular medicine最新文献

{"title":"Revisiting Macrophage Plasticity: From M1/M2 Polarization to Immune Modulation in Cancer Therapy.","authors":"Rasheka Mathur, Yasmin Bano, Anshika Gupta, Sakshi Chauhan, Prince Sharma, Dhananjay Dhar Dwivedi, Rohini Saha, Pramod Kumar, Dinesh Kumar Singhal","doi":"10.2174/0115665240455864260508060735","DOIUrl":"https://doi.org/10.2174/0115665240455864260508060735","url":null,"abstract":"<p><p>Macrophages play a key role in organizing the immune system's response to different types of infections. Their remarkable plasticity enables them to develop and polarize into M1 (tumor-suppressing) and M2 (tumor-promoting) macrophages, in addition to Tumor-Associated Macrophages (TAMs). This thorough review examines how distinct signaling inducers affect macrophage polarization and behavior across various cancer types, including breast, lung, hepatocellular, prostate, and cervical cancers. In colorectal cancer, however, they have the opposite effect and are thought to help keep the tumor microenvironment immunosuppressive. This review also emphasizes how natural and synthetic modulators can prevent tumor growth by altering macrophage function or polarization. These innate immune cells are not only important in cancer but also play a crucial role in autoimmune diseases, allergic responses, and metabolic disorders. Learning about macrophage polarization will help scientists develop drugs that target TAMs, thereby helping tumors shrink.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891189","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":"The Role and Mechanism of AMPK Pathway Activation by NUDT1 in Oral Squamous Cell Carcinoma.","authors":"Haobing Guo, Changsheng Sun, Lili Lu, Bowen Zhao, Yacui Hao, Yihan Gao, Songlin Piao","doi":"10.2174/0115665240483602260824042655","DOIUrl":"https://doi.org/10.2174/0115665240483602260824042655","url":null,"abstract":"<p><strong>Introduction: </strong>This research aimed to investigate the effects of Nudix Hydrolase 1 (NUDT1) on Oral Squamous Cell Carcinoma (OSCC) cells, along with its relationship with the AMP-activated Protein Kinase (AMPK) signaling pathway.</p><p><strong>Methods: </strong>Immunohistochemical methods, Western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to assess the levels of NUDT1 expression in these OSCC tissues and normal tissues. The prognosis of all patients was followed up. The Kaplan‒Meier method was used to analyze the survival rate. Scratch, CCK8, and apoptosis assays were used to analyze the impact of NUDT1 downregulation on cell migration, proliferation, and apoptosis. Western blotting was used to assess AMPK activation after the downregulation of NUDT1.</p><p><strong>Results and discussion: </strong>NUDT1 expression was substantially elevated in OSCC tissues and strongly correlated with pathological grade and tumor stage. All patients with high NUDT1 expression had lower Overall Survival (OS) (P = 0.0259) and Disease-Specific Survival (DSS) (P = 0.0129) rates than patients with low NUDT1 expression (P ＜ 0.05). In addition, the expression of NUDT1 was also greater in both CAL27 and HN30 OSCC cells than in normal cells. Downregulation of NUDT1 expression inhibits the migration and proliferation of Oral Squamous Cell Carcinoma (OSCC) cells and promotes their apoptosis. Furthermore, inhibition of NUDT1 also increased p-AMPK expression.</p><p><strong>Conclusion: </strong>This investigation thoroughly revealed the significance of NUDT1 in OSCC. NUDT1 plays an important role in the proliferation, migration, and apoptosis of OSCC cells and affects the AMPK signaling pathway.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891212","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":"Targeting Klotho Signaling for Neuroprotection in Huntington's Disease: A Comprehensive Review.","authors":"Shikha Singh, Avnesh Kumar, Falguni Goel, Rupesh Kumar Pandey, Lubhan Singh, Dharmendra Kumar, Pramod Kumar Sharma","doi":"10.2174/0115665240475078260817103116","DOIUrl":"https://doi.org/10.2174/0115665240475078260817103116","url":null,"abstract":"<p><strong>Introduction: </strong>HD is a hereditary neurodegenerative disease caused by the amplification of the CAG trinucleotide repeat in the HTT gene, leading to a Mutant Huntingtin (mHTT) protein that dysregulates transcription, promotes protein aggregation, induces neuroinflammation, and impairs mitochondrial function. Motor dysfunction, cognitive decline, and mental disorders are manifestations of these biochemical abnormalities. Effective disease-modifying treatments are still limited, even with recent improvements. This review investigates the increasing relevance of Klotho, an anti-aging protein with neuroprotective, antioxidant, and anti-inflammatory characteristics, as a possible therapeutic target in Huntington disease.</p><p><strong>Methods: </strong>We did a comprehensive literature search across PubMed, Scopus, and Web of Science databases. Klotho's molecular functions in neural protection, energy metabolism, oxidative stress reduction, and anti-inflammatory signalling were investigated in the context of HD pathogenesis.</p><p><strong>Results: </strong>Klotho appears to influence critical neurodegenerative processes involved in HD. It inhibits NF-κB and NLRP3 inflammasome activity, stimulates antioxidant enzyme expression (SOD, catalase), promotes GluN2B-NMDA receptor-mediated synaptic plasticity, and increases astrocytic aerobic glycolysis via FGFR1-ERK signaling. These functions may mitigate mHTT- induced neuronal damage. Pharmacologic treatments (e.g., PPAR-γ agonists), vitamin D, and lifestyle interventions can all modulate klotho expression.</p><p><strong>Discussion: </strong>Klotho exhibits neuroprotective effects in Huntington's disease by reducing NF-κB/NLRP3- mediated inflammation, strengthening antioxidant defenses, promoting GluN2B-NMDA- dependent synaptic plasticity, and improving astrocytic metabolic support via FGFR1-ERK signaling. One intriguing treatment approach for mutant huntingtin-induced neurotoxicity is the modification of klotho expression.</p><p><strong>Conclusion: </strong>Klotho is a promising neurochemical modulator with disease-modifying properties in HD. Its multifunctional protective activities are consistent with important pathological markers of HD, necessitating more preclinical and clinical studies to confirm its translational value.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886222","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":"Exploring the Therapeutic Potential of Bioactive Peptides in Modulating Tau Protein Interactions via the PI3K/Akt Pathway in Neurodegenerative Diseases.","authors":"Kuldeep Singh, Shiv Narayan, Pranshul Sethi, Divya Jain, Jeetendra Kumar Gupta, Mukesh Chandra Sharma, Aman Shrivastava","doi":"10.2174/0115665240423631251207115337","DOIUrl":"https://doi.org/10.2174/0115665240423631251207115337","url":null,"abstract":"<p><p>Neurodegenerative Diseases (NDs) represent a growing global health challenge, characterized by progressive neuronal loss and cognitive decline. Central to these disorders are tauopathies, characterized by abnormal aggregation and hyperphosphorylation of tau proteins, leading to synaptic dysfunction and neuronal degeneration. Among the many intracellular signaling pathways implicated in these processes, the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway plays a pivotal role in neuronal survival, synaptic plasticity, and tau phosphorylation regulation. Dysregulation of this pathway exacerbates oxidative stress, inflammation, and excitotoxic injury, thereby accelerating neurodegeneration. Recent research has highlighted the therapeutic potential of bioactive peptides in modulating tau pathology by targeting the PI3K/Akt cascade. These peptides, derived from natural food sources, marine organisms, and microbial fermentation, exhibit neuroprotective effects through multiple mechanisms, including inhibition of tau aggregation, suppression of proinflammatory mediators, enhancement of antioxidant defenses, and modulation of gut microbiota. Evidence from preclinical studies demonstrates that peptides such as curcumin-derived analogs, resveratrol, and glucagon-like peptide-1 analogs reduce tau phosphorylation and restore neuronal integrity. Furthermore, their ability to interact with signaling molecules such as GSK-3β underscores their promise as disease-modifying agents. Despite these advances, challenges remain, including low bioavailability, rapid metabolism, and limited capacity to cross the blood-brain barrier. Emerging nanotechnology-based delivery systems may overcome these barriers, enhancing peptide stability and therapeutic efficacy. This review summarizes current insights into the molecular interactions between bioactive peptides and tau proteins via the PI3K/Akt pathway and highlights their potential as innovative therapeutic agents for neurodegenerative diseases.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808378","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":"DNA-binding Protein A Inhibitor Improves Cardiac Function After Acute Myocardial Infarction by the Platelet-derived Growth FactorMitogen-activated Protein Kinase-DNA-binding Protein A Signaling Pathway.","authors":"Wu Wang, Jian Wang, Cheng-Ying Yan, Ji-Yu Yang, Fang Gong, Tian-Zhen Wang, De-Kuan Tian","doi":"10.2174/0115665240410376251207172550","DOIUrl":"https://doi.org/10.2174/0115665240410376251207172550","url":null,"abstract":"<p><strong>Introduction: </strong>The present study investigates the regulatory role and underlying mechanisms of DbpA in cardiac function following acute myocardial infarction (AMI).</p><p><strong>Methods: </strong>In Vitro Studies: Primary rat cardiomyocytes and vascular smooth muscle cells (VSMCs) were isolated and characterized using established protocols. Flow cytometry quantitatively assessed apoptosis rates and cell cycle distribution following modulation of the PDGF-MAPK-DbpA pathway. Western blot analysis evaluated the expression levels of pathway components (PDGF, MAPK, DbpA).</p><p><strong>In vivo studies: </strong>An AMI rat model was established through coronary artery ligation. Following pharmacological inhibition of PDGF and MAPK signaling, we assessed cardiac remodeling indices, cardiac function parameters, histopathology, cardiomyocyte apoptosis, and pathway protein expression (PDGF, MAPK, DbpA).</p><p><strong>Results: </strong>In Vitro Studies: Compared with hypoxia-treated controls, both PDGFinhibitor and MAPK-inhibitor treatments resulted in a significant reduction in apoptosis of cardiomyocytes and VSMCs, markedly promoted cellular proliferation, and downregulated protein expression of PDGF, MAPK, and DbpA pathway components.</p><p><strong>In vivo studies: </strong>Relative to ischemia-reperfusion controls, PDGF-inhibitor, MAPKinhibitor, and DbpA-inhibitor interventions consistently yielded improved cardiac functional parameters, reduced myocardial necrosis, and significantly suppressed PDGF, MAPK, and DbpA protein expression.</p><p><strong>Discussion: </strong>DbpA serves as a pivotal regulator in the PDGF-MAPK-DbpA axis, modulating both acute pathological processes and long-term outcomes following myocardial infarction.</p><p><strong>Conclusion: </strong>This study demonstrates that the DbpA inhibitor exerts cardioprotective effects by suppressing cellular apoptosis, promoting proliferation, reducing the heart weight/body weight ratio and left ventricular mass index, limiting necrotic areas, enhancing cardiac functional parameters, and improving myocardial tissue architecture. These beneficial effects are mediated through modulation of the PDGFMAPK-DbpA signaling pathway. Our findings suggest that DbpA represents a promising therapeutic target for preserving cardiac function after AMI and a potential candidate molecule for myocardial protection in acute myocardial infarction.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808398","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":"Circulating Drivers of Pathophysiology in Post-COVID-19 Sequelae.","authors":"Muhammad Abdullah, Anam Naz, Javed Anver Qureshi, Amjed Ali, Muhammad Usman, Ammarah Hasnain, Ayesha Obaid, Ahsan Sattar Sheikh, Leah R Reznikov, Xiao Zhang, Tahir Maqbool","doi":"10.2174/0115665240471871260516074155","DOIUrl":"https://doi.org/10.2174/0115665240471871260516074155","url":null,"abstract":"<p><strong>Introduction: </strong>According to the WHO, post-COVID-19 sequelae impose an increased burden of illness and comorbidities among survivors. The present study evaluated systemic clinical complications associated with the dysregulation of circulatory cytokines in post-COVID-19 patients and compared them with those of healthy controls.</p><p><strong>Methods: </strong>This cross-sectional study included 147 participants divided into symptomatic post-COVID-19, asymptomatic post-COVID-19, and healthy control groups. After obtaining informed consent, peripheral blood samples were collected and analyzed using ELISA and RT-qPCR. Circulating levels of pro-inflammatory (IL-6, IL1β, TNFα) and anti-inflammatory cytokine IL-10 were measured in relation to clinical sequelae.</p><p><strong>Results: </strong>Common symptoms were fatigue (48%), headache (48%), anxiety (64%), general weakness (70%), muscle pain (70%), joint pain (54%), chest pain (32%), dyspnea (36%), and post-activity tachypnea (40%) among post COVID-19 individulas. A higher prevalence of post-COVID-19 sequelae was observed in females aged >40 years and in those with a post-COVID-19 duration of <30 months. ELISA showed higher levels of IL-6, TNF-α, and IL-10 in post-COVID-19 patients than in controls (p < 0.01). RT-qPCR revealed upregulation of IL-6, TNF-α, IL-1β, and IL-10 mRNA, which correlated with post-COVID-19 sequelae (p < 0.01).</p><p><strong>Discussion: </strong>Older age and shorter duration of post-COVID-19 are associated with more symptom burden, implying incomplete immune recovery during early convalescence. Elevated IL-6, IL-1β, TNF-α, and IL-10 levels indicate persistent immune dysregulation, supporting the view that post-COVID-19 is a chronic inflammatory state with clinical effects.</p><p><strong>Conclusion: </strong>IL-6, TNFα, IL-1β, and IL-10 are dysregulated in post-COVID-19 systemic sequelae, and longitudinal studies are necessary to better understand and potentially reduce this dysregulation in post-COVID-19.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808383","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":"The Impact of Microbial Toxins on NRF2 Signaling, Focusing on Stem Cells: Mechanisms and Therapeutic Potential.","authors":"Maryam Darvish, Raheleh Halabian, Reza Kachuei","doi":"10.2174/0115665240446312260723111837","DOIUrl":"10.2174/0115665240446312260723111837","url":null,"abstract":"<p><strong>Introduction: </strong>NF-E2-related factor 2 (NRF2) is a key transcription factor that regulates antioxidant response element (ARE)-driven genes, protecting cells from oxidative damage. Microbial toxins, through mechanisms, such as oxidative stress induction, can activate or inhibit NRF2 signaling. In stem cells, which are highly sensitive to redox imbalance, NRF2 maintains cellular homeostasis while regulating proliferation, differentiation, and metabolism. However, persistent or dysregulated NRF2 activation by toxins may impair differentiation and promote pathological metabolic reprogramming. This review examines how microbial toxins modulate NRF2 signaling, with a focus on stem cells and therapeutic perspectives.</p><p><strong>Methods: </strong>A structured literature review was performed using predefined search terms across major biomedical databases to identify studies investigating microbial toxin- mediated modulation of NRF2 signaling in stem cells. Study selection followed explicit inclusion and exclusion criteria based on stem cell subtype, toxin origin and exposure model, and NRF2-related mechanistic outcomes, including redox regulation. Eligible studies were screened to minimize selection bias and evaluated for methodological quality and relevance, with evidence systematically synthesized to justify stem cell- specific conclusions and therapeutic implications.</p><p><strong>Results: </strong>The protective effects of NRF2 in stem cell biology, while essential for maintaining redox homeostasis and genomic integrity under physiological stress, are highly context-dependent and may shift toward pathological outcomes under chronic or dysregulated activation. NRF2 activation can increase antioxidant defenses, improve bacterial clearance, and promote the resolution of inflammation.</p><p><strong>Discussion: </strong>The NRF2-activating consequences can provide avenues for adjunctive therapy in microbial infections. Moreover, the therapeutic potential of stem cell-based strategies combined with NRF2-targeted interventions is considerable for mitigating microbial toxin-induced damage and enhancing tissue regeneration.</p><p><strong>Conclusions: </strong>Modulating NRF2 activity under microbial toxin exposure is essential to restore redox balance and preserve stem cell function. Future studies should clarify the molecular mechanisms underlying NRF2-targeted interventions to mitigate toxininduced stem cell dysfunction.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808338","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":"Expression Status of ABCC1, an ABC Transporter, as a Potential Biomarker of Disease-Free Survival and Chemotherapy Response in Colon Adenocarcinoma Patients.","authors":"Mukhtiar Ahmad, Samina Ejaz, Iqra Abdullah","doi":"10.2174/0115665240346974251012185121","DOIUrl":"10.2174/0115665240346974251012185121","url":null,"abstract":"<p><strong>Introduction: </strong>The worldwide increasing incidence of colon adenocarcinoma (COAD) due to a lack of early diagnostic biomarkers and drug resistance makes it essential to identify new diagnostic, prognostic, and drug-resistance biomarkers of COAD. ABC transporters are the key players that confer resistance against chemotherapeutic drugs. This study was initiated to explore the diagnostic, prognostic, and therapeutic role of ABCC1 expression in COAD patients.</p><p><strong>Methods: </strong>The cBioPortal database was used to extract the ABCC1 mutation data. Extensive bioinformatics tools were employed to predict the functional impact of mutations. UALCAN was employed to conduct ABCC1 expression, methylation, and overall survival analysis in COAD. Further, pan-cancer analysis was also performed by UALCAN. The correlation of ABCC1 methylation and mutations with overall survival was performed using the OncoDB database. The KM plotter was used for disease-free survival analysis of ABCC1. Meta-survival analysis was conducted using GENT2. The CCLE and GDSC databases were utilized for drug sensitivity analysis of ABCC1 expression in COAD and other cancers.</p><p><strong>Results: </strong>Mutation analysis revealed that ABCC1 harbors damaging and pathogenic mutations in COAD with a frequency of 6%. The expression analysis showed the upregulation of ABCC1 at both transcriptomic and proteomic levels. The ABCC1 promoter was detected to be hypomethylated in COAD patients. Overall survival analysis of ABCC1 expression, methylation, and mutation level showed no significant association with survival in COAD patients. However, disease-free survival analysis showed a significant correlation with ABCC1 expression. Lastly, the drug sensitivity analysis depicted a significant association of ABCC1 expression with reduced drug sensitivity in various cancers.</p><p><strong>Discussion: </strong>The high expression of ABCC1 suggested its role in COAD and highlighted its significance as a therapeutic target.</p><p><strong>Conclusion: </strong>The findings suggested that ABCC1 can be employed as a diagnostic and therapeutic biomarker of COAD and can be used as an indicator of disease-free survival. However, no prognostic potential of ABCC1 in COAD was identified, predicting it as a poor prognostic biomarker of COAD.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705649","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":"Transforming Growth Factor Beta-1 Alleviates Neurodegeneration by Regulating Aβ42 and VDAC1 Expression in the Temporal Lobe and Cerebellum in an Alzheimer's Disease-Like Model.","authors":"Samet Kara, Sema Özandaç, Leman Sencar, Kübra Akillioglu, Sait Polat","doi":"10.2174/0115665240501722260724103809","DOIUrl":"https://doi.org/10.2174/0115665240501722260724103809","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's Disease (AD) has a critical pathology that causes neurodegeneration and mitochondrial dysfunctions via the amyloid deposition. The temporal lobe plays a role in converting sensory input into derived meanings for appropriate processing of visual memory, language comprehension, and emotional association. The cerebellum plays a critical role in the control of motor systems, cognitive, and emotional functions. Aβ42 accumulates between nerve cells in the brain, disrupting synaptic functions and negatively affecting memory and other cognitive functions. VDAC1 is a protein located in the cell membrane that facilitates energy transport to the mitochondria. TGF-β1 is a cytokine that plays a role in many biological functions, including cell growth, differentiation, and tissue repair.</p><p><strong>Objective: </strong>The aim of the study was to investigate the effect of TGF-β1 on scopolamine-induced neurodegeneration of the temporal lobe and cerebellum in experimental AD.</p><p><strong>Methods and results: </strong>The evaluation showed that, according to light and electron microscopic results, edema areas, cytoplasmic vacuolization, and cellular damage were increased in the scopolamine group, while these changes were significantly reduced in the treatment group. According to immunohistochemical findings, the expression levels of Aβ42 and VDAC1 were significantly higher in the scopolamine group than in the control and TGF-β1 groups, while in the treatment group, a low expression was observed compared to the scopolamine group.</p><p><strong>Conclusion: </strong>When all these results are considered together, it has been concluded that TGF-β1 application may regulate the expression of Aβ42 and VDAC1 in critical control centers such as the temporal lobe and cerebellum in a Scopolamin-induced neurodegeneration model, potentially alleviating cellular damage.</p><p><strong>Discussion: </strong>Previous studies have reported that TGF-β1 exerts both antineurodegenerative and neuroprotective effects. In our study, evaluation of the effects of TGF-β1 demonstrated beneficial effects on both mitochondrial damage and amyloid accumulation. Nevertheless, further detailed investigations of these effects may provide valuable insights for future studies.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705602","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":"Exploratory Study on the Role of ILK in the Biological Behavior of Ameloblastoma.","authors":"Ling Bi, Jin Wang, Bo Wang, Jinyan Huang, Huiyong Zhu, Dong Wei","doi":"10.2174/0115665240518837260723105244","DOIUrl":"https://doi.org/10.2174/0115665240518837260723105244","url":null,"abstract":"<p><strong>Introduction: </strong>Ameloblastoma (AM) is a jaw tumor characterized by local invasiveness and a high recurrence rate. Integrin-linked Kinase (ILK) is an important signaling effector proposed as a promising target for cancer therapy. However, its specific role in AM remains poorly understood. This study aimed to investigate the role of ILK in the biological behavior of AM.</p><p><strong>Methods: </strong>ILK expression in AM was examined by Immunohistochemistry (IHC). The GSE132472 dataset from the Gene Expression Omnibus (GEO) database was used to analyze microarray data from AM patient tissues. Gene sets and pathways associated with ILK, as well as differentially expressed genes enriched in AM, were identified. The effects of the ILK inhibitor Cpd22 on AM cell proliferation, adhesion, and migration were assessed.</p><p><strong>Results: </strong>AM tissues exhibited elevated ILK and integrin β1 expression and decreased E-cadherin expression, along with a trend towards the upregulation of ILK at the transcriptional level. Gene sets directly or indirectly related to ILK, including EMT, Extracellular Matrix (ECM) organization, integrin signaling, and focal adhesion, were closely associated with AM, while the PI3K-Akt signaling pathway was the most significantly upregulated in AM. Differentially expressed genes enriched in these pathways were involved in cell proliferation, adhesion, migration, and cytoskeletal regulation. In vitro experiments showed that Cpd22 significantly inhibited the adhesion and migration of AM cells.</p><p><strong>Discussion: </strong>The study's findings reveal an inverse correlation between ILK and Ecadherin expression intensity in AM, consistent with observations in other malignancies. ILK may contribute to AM pathogenesis through coordinated interactions with focal adhesions, integrins, and the ECM. It is also involved in AM cell adhesion and migration without affecting proliferation and may also participate in Akt phosphorylation and cytoskeletal regulation in AM cells.</p><p><strong>Conclusion: </strong>The study's findings indicate that ILK plays a role in modulating the biological behavior of AM.</p>","PeriodicalId":10873,"journal":{"name":"Current molecular medicine","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148600018","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}