Research in Pharmaceutical Sciences最新文献

Background and purpose: Decellularized extracellular matrix (dECM) scaffolds offer advanced platforms for studying breast and prostate cancer, enabling the replication of the tumor microenvironment (TME) with high fidelity. This review summarizes methodologies for creating dECM scaffolds, highlighting their biochemical and mechanical properties that enable up to 70% greater physiological relevance compared to traditional two-dimensional cultures.

Search strategy: A systematic literature search was conducted on PubMed, Scopus, and Web of Science databases (2010-2025) using keywords such as "decellularized extracellular matrix," "breast cancer," "prostate cancer," and "tumor microenvironment." Inclusion criteria focused on peer-reviewed studies employing dECM scaffolds in breast and prostate cancer research.

Findings: Key findings reveal that dECM scaffolds effectively mimic tissue-specific TMEs, facilitating the study of tumor-stroma interactions, cellular responses, and drug resistance in breast and prostate cancers. dECM supports enhanced understanding of cancer progression mechanisms, including increased invasiveness, chemoresistance, and cell proliferation. Differences in decellularization methods influence ECM composition and scaffold function. Challenges, including standardization, clinical validation, and scalability, remain.

Conclusion and future trends: dECM scaffolds hold great potential to advance cancer biology research and precision therapy development by providing biomimetic platforms. Future directions include integrating bioengineering advancements, AI-assisted ECM analysis, organoid and organ-on-chip models, and enhanced decellularization protocols to improve model fidelity and clinical relevance.

Background and purpose: Breast cancer is a major global concern, especially because of high mortality linked to advanced stages. Metastasis may occur early, but current diagnostics struggle to detect small metastatic cells. Non-invasive liquid biopsies, such as circulating miRNA, ctDNA, and cfDNA, present a promising solution for screening and monitoring breast cancer. This study aimed to examine the clinical relevance of circulating levels of cfDNA, miR-182, CYFRA21-1, and CEA in metastatic and non-metastatic breast cancer patients and their association with clinical stage and distant metastasis.

Experimental approach: Ten mL blood samples were collected from 17 metastatic and 29 non-metastatic breast cancer patients pre-surgery. cfDNA was measured fluorometrically, miRNA-182 via quantitative real-time PCR, CYFRA21-1, and CEA using enzyme-linked immunosorbent assay ELISA.

Findings/results: Results demonstrated significantly higher levels of cfDNA, miR-182, CYFRA21-1, and CEA in women with metastatic breast cancer compared to those with non-metastatic breast cancer. These markers were linked to advanced clinical stages and increased tumor size. Elevated levels of cfDNA, miR-182, and CYFRA21-1 were indicative of a higher risk for lymphatic metastasis, while cfDNA and CYFRA21-1 were associated with distant metastasis. ROC curve analyses revealed strong efficacy for cfDNA (AUC 0.94), miR-182 (AUC 0.91), CYFRA21-1 (AUC 0.88), and CEA (AUC 0.87) in detecting metastatic breast cancer.

Conclusion and implications: Combined analysis of these biomarkers will enhance the predictive accuracy of metastatic breast cancer and clarify the relationship between biomarker profiles and the characteristics of metastatic versus nonmetastatic patients using liquid biopsy technology.

Background and purpose: Spinal cord injury (SCI) causes motor and cognitive impairments, with secondary hippocampal damage contributing to memory deficits. This study examined the effects of neural stem cell (NSC)-laden polyurethane/functionalized multiwalled carbon nanotube (PU/f-MWCNT) scaffolds coated with liposomal hesperidin (Hsd@lip) on hippocampal synaptic integrity, neuroinflammation, and memory in a rat model of dorsal hemisection SCI.

Experimental approach: Electrospun PU/f-MWCNT scaffolds were prepared and loaded with NSCs, Hsd@lip, or both. Wistar rats (n = 15/group) were assigned to untreated SCI, scaffold+Hsd@lip (PCH), scaffold+NSC (PCN), or scaffold+NSC+Hsd@lip (PCHN). Four weeks post-implantation, hippocampal synaptic plasticity, oxidative stress, neuronal survival, and memory performance were evaluated using electrophysiology, biochemical assays, histology, and behavioral tests.

Findings/results: The scaffolds were uniform, bead-free fibers with an average diameter of 174.7 ± 63.5 nm. Hsd@lip coating formed a thin, non-aggregated layer that maintained scaffold porosity. Cell seeding demonstrated good NSC adhesion and spreading, supporting the scaffold's biocompatibility. Compared to the SCI group, animals treated with PCHN exhibited a significant reduction in MDA levels and decreased AChE activity, and increased thiol content. Doublecortin expression markedly increased, while NF-κB levels and dark neuron counts significantly reduced. Furthermore, cognitive function improved.

Conclusion and implications: These findings highlight the potential of NSC-laden PU/f-MWCNT scaffolds coated with Hsd@lip to mitigate hippocampal damage, restore synaptic integrity, and improve cognitive function following SCI. This multimodal approach offers a promising therapeutic strategy for addressing the cognitive sequelae of SCI.

Background and purpose: Cadmium (Cd) inhibited osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), while catechin hydrate (CH) improved the osteo-differentiation. Meanwhile, this investigation aimed to study the compensating effect of CH on Cd inhibition.

Experimental approach: BMSCs from Wistar rats were treated with Cd and CH, and then the viability and population doubling number were investigated. Based on them, 1.5 μM and 0.25 μM of Cd and CH were chosen, respectively. Following osteogenic induction, matrix production, expression of osteogenic-related genes, and expression of collagen-1 (COL1-A1) protein were analyzed. Moreover, the ability of CH to prevent Cd-induced oxidative stress, as well as the metabolic activity of the treated cells, was evaluated.

Findings/results: The selected concentration of CH significantly ameliorated Cd-induced inhibition of BMSCs osteo-differentiation through preventing oxidative stress and ameliorating gene expression. Indeed, CH in the co-treatment group significantly improved the expression of Smadl, Bmp2, Runx2, Oc, Alp, Col-1 genes as well as the production of COL 1-A1 protein compared to the control group. Moreover, the co-treatment of CH and Cd significantly decreased MDA levels and boosted TAC levels and CAT, SOD activity compared to the control group. CH compensated for the Cd-induced metabolic changes as LDH, ALT, and AST activities significantly improved to the control level.

Conclusion and implications: CH prevented oxidative stress and counteracted the inhibitory effect of Cd on the osteogenic differentiation of BMSCs. Therefore, CH may be suggested to prevent Cd toxicity on bone.

Background and purpose: Excessive and long-term consumption of alcohol causes health problems and significant changes in the physiological and biochemical functions of the body organs, including the kidneys. The present study aimed to clarify and investigate the antioxidant and anti-inflammatory impacts of Stachys pilifera Benth (SPB) hydroalcoholic extract on ethanol (EtOH)-induced nephrotoxicity.

Experimental approach: Twenty-four rats were randomly divided into 4 groups. The control group was administered distilled water as a vehicle for 35 days. The EtOH group received ethanol (40% v/v, 7 mL/kg) orally for 35 days. The SPB extract + EtOH group was pretreated with 500 mg/kg of SPB orally and, after 1 h, received ethanol (40% v/v, 7 mL/kg) orally for 35 days; the SPB extract group received only 500 mg/kg of SPB for 35 days. After 35 days, the rats were sacrificed, and the blood sample was taken. Then, levels of biochemical markers, oxidative stress indices, antioxidant enzyme activity, and pro-inflammatory cytokines were evaluated.

Findings/results: In the EtOH group, the levels of BUN, Cr, NO metabolite, and MDA were significantly higher compared to the control group. In addition, a significant elevation in the levels of pro-inflammatory cytokines (TNF-α and IL-6) was observed compared to the control group. Pretreatment with SPB hydroalcoholic extract led to significant diminishment in BUN, Cr, MDA, NO metabolite, and TNF-α and IL-6.

Conclusion and implications: The hydroalcoholic extract of SPB led to improvement of kidney function, reduction of oxidative stress, and improvement of inflammatory conditions in nephrotoxicity caused by ethanol in male rats.

Background and purpose: Patient-derived tumor 3D multicellular cultures are a novel non-small cell lung cancer (NSCLC) model for studying tumor biology and precision medicine, which recapitulates tumor morphology and gene expression profile. However, practical application is challenged by issues such as low establishment rates, long-term production difficulties, and the absence of immune microenvironment components. To address these issues, this study aimed to evaluate the efficacy of a novel method for generating free-floating patient-derived organotypic tumor spheroids (PDOTS) using a stimuli-responsive extracellular matrix (ECM)-mimicking gel.

Experimental approach: Free-floating PDOTS were established from 18 NSCLC tumors and characterized by their morphology, marker expression, and extracellular matrix composition. Cell composition in PDOTS and their parental tumors was analyzed by flow cytometry, while RT-PCR was used to assess the expression of genes encoding signaling molecules. Finally, drug response and the expression of drug resistance genes were evaluated in the NSCLC PDOTS.

Findings/results: The PDOTS were successfully generated with a success rate exceeding 90%, forming spheroids within one week. These PDOTS preserved the parental tumor's morphology and included stromal and immune cells. Notably, 58% of the PDOTS maintained cytokine and growth factor expression profiles closely mimicked those of the original tumors. Furthermore, the PDOTS demonstrated varied responses to anticancer drugs, potentially influenced by differential expression of drug resistance-associated genes.

Conclusion and implications: The high establishment rate and rapid production timeline of free-floating PDOTS using a stimuli-responsive ECM-mimicking gel make this approach a promising tool for advancing cancer biology research and evaluating therapeutic strategies with greater accuracy.

Background and purpose: Aging is a dynamic and progressive loss of physiological integrity that leads to irreversible changes in cells and tissues, thereby increasing the risk of disability, disease, and death. Previous studies have provided evidence that D-galactose (D-gal) mimics the natural aging process in humans. On the other hand, it has been shown that α-lipoic acid (α-LA) acts as an anti-inflammatory and antioxidant compound. Therefore, this study aimed to investigate the protective effects of α-LA on D-gal-induced cellular senescence in SH-SY5Y neuroblastoma cells.

Experimental approach: Senescence was induced in SH-SY5Y cells by D-gal, and the protective effects of α-LA against D-gal toxicity were evaluated by the assays of β-galactosidase, reactive oxygen species (ROS), and antioxidant parameters in SH-SY5Y cells. In addition, the mRNA expression of Bax, Bcl-2, and p53 genes was evaluated using qRT-PCR.

Findings/results: The results revealed that α-LA at the concentrations of 62.5 and 125 μM reduced the cytotoxicity and senescence caused by D-gal. α-LA also effectively reduced the ROS generation compared to the D-gal group. Treatment with α-LA significantly modulated the levels of malondialdehyde, total thiol, and superoxide dismutase activity, which were altered by D-gal. In addition, treatment with α-LA decreased the expression of Bax and p53 genes, while increasing the expression of the Bcl-2 gene.

Conclusion and implications: Overall, the results showed that α-LA could moderate the toxic effects of D-gal by increasing the antioxidant capacity and modulating the genes involved in apoptosis, and it deserves further studies.

Background and purpose: Linifanib is a multi-targeted receptor tyrosine kinase inhibitor. Although it is widely recognized for its efficacy in inhibiting receptor tyrosine kinases, its anticancer effects in ovarian cancer have not been extensively studied. In this study, we investigated the anticancer effects of linifanib on human ovarian cancer OVCAR3 cells.

Experimental approach: To evaluate cell proliferation capacity, we performed MTT assays, cell counting, morphological analysis, and colony formation assays. Flow cytometry was used to assess the induction of apoptotic cells by linifanib, and DNA fragmentation was evaluated using TUNEL assays. Western blotting was performed to determine the protein expression levels related to apoptosis.

Findings/results: Our results demonstrated that linifanib significantly inhibited the proliferation of OVCAR3 cells and induced apoptosis. Notably, treatment with linifanib led to the inhibition of phosphorylated Akt at Ser473, accompanied by the activation of FOXO3.

Conclusion and implications: Taken together, these findings indicate that linifanib suppresses the proliferation of human ovarian cancer OVCAR3 cells, highlighting its potential as a therapeutic candidate for ovarian cancer treatment.

Background and purpose: Prostate cancer is one of the most common cancers in the world. Anti-prostate cancer drugs such as docetaxel, doxorubicin, and cabazitaxel have drawbacks resulting from their low solubility, non-targeted transfer, and many side effects. Prostate-specific membrane antigen (PSMA) receptor is expressed on the surface of prostate cancer cells. It was known that "WQPDTAHHWATL" and "GRFLTGGTGRLLRIS" peptides tended to bind this receptor.

Theoretical approach: "WQPDTAHHWATL" and "GRFLTGGTGRLLRIS" peptides were attached to the C and N tails of albumin protein, and an engineered albumin was designed. Then, engineered albumin and the extracellular domain of PSMA were separately simulated for 100 ns. Afterward, the interaction of engineered albumin with anti-prostate cancer drugs and the PSMA domain was investigated independently by molecular docking, molecular dynamics simulation, and molecular mechanics energies/Poisson-Boltzmann surface area binding free energy methods.

Findings/results: The binding affinity order of drugs to engineered albumin was docetaxel, doxorubicin, and cabazitaxel, respectively. Also, the residence time of docetaxel was longer than that of other drugs. The final picture of complexes showed that cabazitaxel and docetaxel bound to site IB, and doxorubicin bound to site IIA of the recombinant albumin. Additionally, the C-terminus and N-terminus of the engineered albumin could bind to the PSMA receptor.

Conclusion and implications: It can be concluded that this engineered albumin is useful for targeted drug delivery in prostate cancer.

Background and purpose: Carbon quantum dots (CQDs) have garnered significant interest in various fields as a burgeoning category of photoluminescent nanomaterials. The current study involved the synthesis of photoluminescent carbon dots through the hydrothermal processing of garlic (Allium sativum L.) juice, serving as a naturally derived carbon source.

Experimental approach: The morphology and optical properties of the carbon dots were characterized by TEM, XRD, FT-IR, XPS, UV-Vis, and photoluminescence. The cytotoxic and apoptotic effects of CQDs were evaluated in A549, SKNMC, and H1299 (p53 null) human carcinoma cell lines.

Findings/results: The TEM findings confirmed that carbon dots exhibit a limited variability in their size distribution, characterized by mean diameters of around 16.3 ± 2.7 nm. The peak emission wavelength of carbon dots was observed at 400 nm, accompanied by an excitation peak at 320 nm, and their quantum yield in aqueous solution was measured to be 11.5%. The garlic CQDs were proven to be extremely potent cytotoxic agents, especially against H1299 cells. Apoptosis induction by CQDs was accompanied by an increase in activation of caspase-3 and caspase-9, as well as the disruption of mitochondrial membrane potential in H1299 cells.

Conclusion and implications: The apoptotic potential of garlic CQDs was evaluated in the most sensitive cell line, H1299. The apoptogenic effect of garlic CQDs on H1299 cells is important because it has been demonstrated that the loss of p53 is associated with poor clinical prognosis in cancer treatment.