Inorganic Nanoparticles and Blood-Brain Barrier Modulation: Advancing Targeted Neurological Therapies

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 287, P. 117357 - 117357

Published: Feb. 5, 2025

Language: Английский

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Human endometrial stem cell-derived small extracellular vesicles enhance neurite outgrowth and peripheral nerve regeneration through activating the PI3K/AKT signaling pathway

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 3, 2025

Nowadays, extracellular vesicles (EVs) such as exosomes participate in cell-cell communication and gain attention a new approach for cell-free therapies. Recently, various studies have demonstrated the therapeutic ability of exosomes, while biological effect human endometrial stem cell (hEnSC)-derived small EVs is still unclear. Herein, we obtained from hEnSC indicated that these activate vital signaling pathway progress neurite outgrowth PC-12 lines. For this purpose, hEnSC-derived were extracted by ultracentrifuge characterized DLS, SEM, TEM, western blot. Also, dil-staining was done to determine penetration into PC12 cells. The MTT assay, scratch blot assay applied cells exposed different concentrations (0, 50, 100, 150 µg/ml). Our results significantly increased outgrowth, proliferation, migration dose-dependent manner. Moreover, analysis blots showed expression PI3k/AKT study can enhance proliferation promote neural activating pathway. Accordingly, became an effective strategy Altogether, positive effects make efficient regenerative medicine, especially cure injury.

Language: Английский

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Pharmacological, computational, and mechanistic insights into triptolide’s role in targeting drug-resistant cancers

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 25, 2025

Language: Английский

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CDCA genes as prognostic and therapeutic targets in Colon adenocarcinoma

Hereditas, Journal Year: 2025, Volume and Issue: 162(1)

Published: Feb. 10, 2025

Abstract Objectives The study investigates the role of Cell Division Cycle Associated (CDCA) genes in colorectal cancer (COAD) by analyzing their differential expression, epigenetic alterations, prognostic significance, and functional associations. Methodology This employed a detailed silico vitro experiments-based methodology. Results RT-qPCR assays reveal significantly elevated mRNA levels CDCA2, CDCA3, CDCA4, CDCA5, CDCA7, CDCA8 COAD cell lines compared to controls. Bisulfite sequencing indicates reduced promoter methylation CDCA gene promoters lines, suggesting an regulatory mechanism. Analysis large TCGA datasets confirms increased expression tissues. Survival analysis using cSurvival database demonstrates negative correlations between patient overall survival. Additionally, Lasso regression-based models predict survival outcomes patients. Investigating immune modulation, inversely correlates with infiltration modulators. miRNA-mRNA network identifies miRNAs targeting genes, validated showing up-regulation has-mir-10a-5p has-mir-20a-5p Drug sensitivity suggests resistance specific drugs patients expression. Furthermore, crucial states COAD, including “angiogenesis, apoptosis, differentiation, hypoxia, inflammation, metastasis.” Additional experiments revealed that CDCA2 CDCA3 knockdown SW480 SW629 cells proliferation colony formation while enhancing migration. Conclusion Overall, elucidates multifaceted progression, providing insights into potential diagnostic, prognostic, therapeutic implications.

Language: Английский

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Exploring MAP3K genes in gastric cancer: biomarkers, tumor microenvironment dynamics, and chemotherapy resistance

Hereditas, Journal Year: 2025, Volume and Issue: 162(1)

Published: Feb. 3, 2025

Gastric cancer (GC) presents a significant global health burden, necessitating deeper understanding of its molecular underpinnings for improved diagnostics and therapeutics. In this study, we investigated the expression profiles clinical implications MAP3K genes in GC using silico vitro experiments. Utilizing RT-qPCR analysis, observed up-regulation MAP3K1, MAP3K4, MAP3K5, MAP3K6, MAP3K7, MAP3K8, MAP3K9, MAP3K10 cell lines, while MAP3K2, MAP3K3, MAP3K11, MAP3K12, MAP3K13, MAP3K14, MAP3K15 exhibited down-regulation. Prognostic evaluation revealed that elevated was associated with shorter overall survival (OS), emphasizing their significance. Furthermore, diagnostic potential demonstrated through robust Receiver operating characteristics (ROC) curve indicating strong discriminatory power these distinguishing patients. Proteomic analysis further confirmed higher GC. Methylation profiling supported idea promoter hypomethylation up-regulation. Single-cell functional elucidated involvement shaping tumor microenvironment. miRNA-mRNA network intricate regulatory mechanisms, hsa-mir-200b-3p emerging as key regulator. Finally, MAP3K1 knockdown has shown impacts on cellular behavior BGC823 cells. This comprehensive assessment provides valuable insights into role GC, offering avenues research therapeutic exploration.

Language: Английский

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Harnessing the FOXO-SIRT1 axis: insights into cellular stress, metabolism, and aging

Biogerontology, Journal Year: 2025, Volume and Issue: 26(2)

Published: Feb. 26, 2025

Language: Английский

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Designing novel cabozantinib analogues as p-glycoprotein inhibitors to target cancer cell resistance using molecular docking study, ADMET screening, bioisosteric approach, and molecular dynamics simulations

Frontiers in Chemistry, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 27, 2025

One of the foremost contributors to mortality worldwide is cancer. Chemotherapy remains principal strategy for cancer treatment. A significant factor leading failure chemotherapy phenomenon multidrug resistance (MDR) in cells. The primary instigator MDR over expression P-glycoprotein (P-gp), a protein that imparts and facilitates ATP-dependent efflux various anticancer agents. Numerous efforts have been made inhibit P-gp function with aim restoring effectiveness due its broad specificity. main objective has create compounds either serve as direct inhibitors or interact therapies modulate transport. Despite substantial vitro achievements, there are currently no approved drugs available can effectively "block" mediated resistance. Cabozantinib (CBZ), multi-kinase inhibitor, utilized treatment carcinomas. CBZ shown activity, thereby reversing MDR. Consequently, emerged critical target research anti-cancer therapies. purpose this study was computationally identify new andsafer analogues using bioisosteric approach, focusing on improved pharmacokinetic properties andreduced toxicity. physicochemical, medicinal, ADMET profiles generated were computed ADMETLab 3.0 server. We also predicted drug likeness (DL) score (DS) analogues. molecular docking studies screened against (PDB ID: 3G5U) conducted AutoDock Vina flowing by BIOVIA Discovery Studio visualizing interactions.Molecular dynamics (MD) simulation docked ligands done Schrödinger suite. scores CBZ01, CBZ06, CBZ11, CBZ13, CBZ25, CBZ34, CBZ38 ranged from -8.0 -6.4 kcal/mol 3G5U). suite, revealing these complexesmaintained stability throughout 100 ns simulation. An integrated computational approach combining docking, calculations, MD simulations highlights promise CBZ01 CBZ13 candidates development potential agents cancers.

Language: Английский

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From protein to immunology: comprehensive insights into Marburg virus vaccines, mechanism, and application

Archives of Microbiology, Journal Year: 2025, Volume and Issue: 207(4)

Published: March 1, 2025

Language: Английский

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4-Phenylthiazol-1,2,3-triazole derivatives as new potential α-glucosidase and α-amylase inhibitors

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: unknown, P. 141919 - 141919

Published: March 1, 2025

Language: Английский

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Integrative bioinformatics analysis of high-throughput sequencing and in vitro functional analysis leads to uncovering key hub genes in esophageal squamous cell carcinoma

Hereditas, Journal Year: 2025, Volume and Issue: 162(1)

Published: March 14, 2025

Abstract Background Esophageal squamous cell carcinoma (ESCA) is a type of cancer that starts in the cells lining esophagus, tube connecting throat to stomach. It known for its aggressive nature and poor prognosis. Understanding key factors drive this crucial developing better diagnostic tools treatments. Methods Gene expression profiles ESCA were analyzed using Expression Omnibus (GEO) datasets (GSE23400, GSE29001, GSE92396, GSE1420) from GEO database. Differentially expressed genes (DEGs) identified limma package, protein-protein interaction (PPI) network was constructed STRING Hub based on degree method. Further validation performed through reverse transcription quantitative PCR (RT-qPCR), mutational copy number variation (CNV) analysis via cBioPortal database, promoter methylation OncoDB GSCA databases, survival analysis, immune infiltration functional assays, including knockdown genes. Results We four hub genes, COL3A1, COL4A1, COL5A2, CXCL8 play significant roles ESCA. These highly tissues lines, with levels significantly (p-value < 0.001) elevated compared normal controls. Receiver operating characteristic (ROC) curve revealed exceptional performance all area under (AUC) values 1.0, indicating perfect sensitivity specificity distinguishing Mutational COL3A1 altered 67% samples, primarily missense mutations, while COL5A2 exhibited alterations 50% splice site mutations. Additionally, gene amplification patterns observed further validating their oncogenic potential progression. A 0.05) hypomethylation detected these suggesting regulatory role expression. Functional assays demonstrated knocking down COL4A1 led decreased proliferation, colony formation, migration, critical tumor involved pathways related extracellular matrix system modulation. Conclusion are development progression, particularly remodeling matrix, modulating system, promoting metastasis. findings suggest could serve as biomarkers diagnosing targets future therapies. Future research should focus vivo clinical testing assess therapeutic targeting treatment.

Language: Английский

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