Colorectal cancer (CRC) represents a leading cause of cancer morbidity and mortality globally. Tschimgine (Tsc), a naturally occurring terpenoid from Ferula ovina, has exhibited potent anticancer activity in preclinical models. However, its ability to enhance the sensitivity of CRC cells to 5-Fluorouracil (5-FU) remains unexplored. This study examined the pro-apoptotic and anti-metastatic properties of Tsc, both individually and in combination with 5-FU, in HT-29 human colorectal adenocarcinoma cells. HT-29 CRC cells and HFF human fibroblast cells were treated with Tsc, 5-FU, or their combination. Cell viability was assessed using the MTT assay. Apoptotic activity and cell cycle distribution were evaluated through flow cytometry. Migration capacity was tested using a scratch wound healing assay. Expression of apoptosis-related (Bax and Bcl-2) and metastasis-related genes (MMP-2 and MMP-9) was measured by qRT-PCR. Co-treatment with Tsc and 5-FU demonstrated a synergistic, dose-dependent reduction in HT-29 cell viability with minimal cytotoxicity toward HFF cells. Apoptosis was markedly enhanced in the combination group, evidenced by upregulated Bax and downregulated Bcl-2 expression. The combination also led to marked inhibition of cell migration and downregulation of MMP-2 and MMP-9. Tsc enhances 5-FU efficiency in inhibiting the growth and metastatic potential of HT-29 colorectal cancer cells. These results show the promising therapeutic effects of the combination of these two drugs, and more studies are needed to confirm their clinical use in the treatment of CRC.

Folate receptors, which mediate the cellular uptake of folic acid (FA) for essential processes such as DNA synthesis and repair, are expressed on neurons affected in Parkinson’s disease (PD). While the etiology of PD remains incompletely understood, oxidative stress is implicated as a key contributor. Alpha-lipoic acid (ALA) is a potent antioxidant; however, its therapeutic application is limited by instability, low bioavailability, and an unpleasant odor. Nanotechnology offers a promising strategy to overcome these limitations. This study aimed to develop and characterize folic acid-conjugated chitosan nanoparticles encapsulating ALA (FA-CS-ALA NPs) and to evaluate their efficacy against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity. The FA-CS-ALA NPs, characterized by transmission electron microscopy, exhibited an irregular spherical morphology. Dynamic light scattering (DLS) analysis determined an average particle size of 658.13 nm and a polydispersity index (PDI) of 0.17, indicating moderate size distribution. In vitro studies using SH-SY5Y neuroblastoma cells demonstrated that 6-OHDA exposure significantly increased oxidative stress, neuroinflammation, and apoptosis. Both free ALA and FA-CS-ALA NPs effectively mitigated these deleterious effects. Notably, the FA-CS-ALA NPs exhibited superior neuroprotective efficacy compared to free ALA, suggesting that the folate-conjugated nanocarrier enhances therapeutic delivery.

Objective:Destruction of dopaminergic neurons causes diseases. Various compounds with neuroprotective and antioxidant properties have been identified, including Hesperidin (HES) and Auraptene (AUR). We aimed in this study to evaluate the in vitro protective effects of these compounds in SH-SY5Y neuroblastoma cell line against the induced neurotoxicity of 6-hydroxydopamine (6-OHDA). Materials and Methods:The MTT test to assess cell viability was used. Flow cytometry was conducted for the cell cycle analysis using propidium iodide (PI) stain. The intracellular production of reactive oxygen species (ROS) was assessed using 2, 7'-dichlorofluorescein diacetate (DCFDA) probe and fluorimetry. Results:Following 6-OHDA treatment, cell viability decreased, and G2/M arrest and ROS levels increased. Our intervention demonstrated that only HES has neuroprotective effects against 6-OHDA-induced toxicity. Conclusion:HES protects SH-SY5Y cells against 6-OHDA-induced neural damage via inhibiting G2/M arrest, reducing the amount of ROS, and increasing cell viability. However, the different effects and more precise mechanisms are still unknown, and requires new research on animal and human models.

Osteosarcoma (OS), an extremely aggressive form of bone tumor primarily affects young adults. Despite significant advancements in clinical trials, the ability of cancer cells to metastasize and resist apoptosis remains a major challenge. To address these issues, novel therapeutic interventions with high specificity for these processes are essential. Alpha-lipoic acid (ALA), an organosulfur compound derived from octanoic acid, possesses a range of pharmacological properties. This study hypothesizes that ALA would inhibit metastasis and induce cell apoptosis in OS. To evaluate the potential of ALA, its effects on the migration, metastasis, and cell cycle of MG-63 OS cells were assessed, along with its ability to trigger apoptosis. To these aims, MG-63 cells were exposed to varying concentrations of ALA, and cell viability was measured using the alamarBlue assay. The impact of ALA on cell cycle progression, apoptosis, migration, and metastasis was analyzed through flow cytometry, scratch assay, and gelatin zymography. After validating the expression of MMP2, MMP9, VEGF, VEGFR, BAX, BCL-2, and P53 by the GEO database, the expression levels of these genes were examined through quantitative PCR (qPCR). Eventually, molecular docking was employed to simulate the interactions between ALA and matrix metalloproteinase (MMPs). The results demonstrated that ALA significantly inhibited cell migration, induced cell cycle arrest, and promoted apoptosis by upregulating P53 and BAX expression while downregulating BCL-2 levels. Furthermore, ALA was found to suppress the activity and expression of MMP2 and MMP9 and reduce the expression of angiogenesis markers. Notably, ALA interacted directly with the active site of MMP2 and MMP9. These findings suggest that ALA has the potential to be a promising agent with anti-cancer effects on MG-63 cells, warranting further preclinical investigations.

Cancer remains the second leading cause of death worldwide, posing a significant global health challenge. Extensive research has revealed common biological characteristics across cancer cells, forming the foundation for developing innovative diagnostic and therapeutic strategies. To better understand these shared traits, advanced measurement technologies are critical. Proteomics, the large-scale study of proteins and their functions, has emerged as a transformative tool for uncovering the complexities of cancer biology. This approach provides an in-depth view of cellular activities and protein interactions, offering unprecedented insights into cancer progression and treatment. Unlike traditional methods that investigate specific pathways in isolation, proteomics enables simultaneous analysis of thousands of proteins, generating a comprehensive understanding of cancer biology. This review explores the mechanisms underlying proteomics, its application to understanding cancer hallmarks, and its potential to transform clinical approaches. By examining proteomics' role in metastasis, angiogenesis, proliferation, and resistance mechanisms, this study highlights its contributions to cancer diagnosis, treatment, and personalized medicine. Additionally, prospects in integrating proteomics with other -omics fields and advancements in computational analysis will be discussed. This work aims to illuminate the path toward more effective, precise, and individualized cancer care through proteomics innovations.

Parkinson's disease (PD) is a degenerative central nervous system disease pathologically attributed to dopaminergic neuron damage in the substantia nigra. Noscapine is a natural alkaloid with several benefits, including anti-inflammatory, neural protection, and anti-oxidant effects. Hence, the current study evaluated the protective effects of Noscapine against paraquat (PQ)-induced Parkinson's disease model in rats. Male Wistar rats were into six groups: sham and PQ-induced models treated with vehicle, vitamin-E (20 mg/kg/d), or Noscapine (6, 18, and 55 mg/kg/d) for four weeks. Meanwhile, the rats were assessed for weight and food consumption (FC) daily and PD-associated behavior changes using rotarod, bar, and parallel bar tests every week. The animals were ethically sacrificed at the end of the study, and biochemical, immunological, and histopathological markers were measured in the brain. As a result, the levels of weight, FC, parallel bar, and rotarod test (both speed and latency), number of neurons, total thiol content, and interleukin-10 (IL-10) were significantly reduced. In contrast, the levels of dark neurons, TNF-α, bar test, and malondialdehyde (MDA) were markedly increased in the PQ-vehicle group compared to the sham group (P < 0.001–0.5). In contrast, comedication with Noscapine significantly reversed the histological damages and improved deteriorated behavioral, biochemical, and immunological parameters in a dose-dependent manner compared to the PQ-vehicle group (0.001–0.05). Taken together, it was determined that using Noscapine has antiparkinsonian effects and improved behavioral tests, catalepsy, bradykinesia, and motor dysfunction and has a protective impact on the brain's neurons through its anti-oxidant and anti-inflammatory properties.

Glioblastoma (GBM), the most aggressive primary brain tumor, faces significant treatment challenges due to drug resistance, blood–brain barrier limitations, and severe side effects of conventional therapies. This study aimed to develop and evaluate a nanotechnology-based therapeutic approach using selenium-loaded β-cyclodextrin-combretastatin A-4 nanoparticles (Se(B-CD-CA-4-NPs)) to overcome these limitations and enhance treatment efficacy. The Se(B-CD-CA-4-NPs) complex was synthesized and characterized for morphology, size, stability, and selenium loading capacity. In vitro studies included MTT assay, cell apoptosis, scratch assay, gelatin zymography, and qPCR were used to assess the effect of the newly synthesized complex on U-87MG glioblastoma cell viability, cell death, migration, MMP-2 and MMP-9 activity, and mRNA expression level of apoptosis-related genes. The nanoparticles exhibited a spherical morphology (25.78 ± 3.4 nm), negative surface charge, and high stability. The IC50 of the synthesized complex was 1.629 μM in U-87MG cancer cells. The Se(B-CD-CA-4-NPs) complex significantly reduced U-87MG cell viability, migration and invasion. Additionally, the complex induced cell apoptosis via upregulation of the BAX/BCL-2 ratio in cancer cells. Moreover, the Se(B-CD-CA-4-NPs) complex inhibited metastasis by suppressing the activity and expression of MMP-2 and MMP-9. The Se(B-CD-CA-4-NPs) complex represents a promising multifunctional therapeutic agent for GBM, offering enhanced proapoptotic property, selective tumor targeting, and reduced toxicity.

BACKGROUND:MicroRNAs (miRNAs) are a group of small non-coding RNAs that substantially participate in regulating gene expression. Their participation in cancer development encompasses various critical pathways, spanning from cell transformation to the progression of tumor cells, metastasis, and even resistance to treatment. This study aimed to assess the impact of miR-206 on radiosensitivity in breast cancer (BC) cells, SIRT1 activity, and p53 acetylation. METHOD:miR-206 mimic or inhibitor was transfected into BC cell lines and exposed to X-ray radiation. MTT and colony-forming assays were used to estimate cell viability, and apoptosis was inspected using flow cytometry. SIRT1 enzymatic activity was assessed by a fluorescence method. The protein levels of p53 and its acetylation status were evaluated using western blotting. miR-206 levels were assessed in the breast tumor, marginal, and normal control tissue. RESULTS:The expression of miR-206 was significantly reduced in BC cell lines and tumor tissue compared to normal tissue. miR-206 reduced cell viability and induced apoptosis, and could enhance the suppressive effects of irradiation on cell viability, colony formation, and its ability to induce apoptosis. miR-206 effectively suppressed SIRT1 activity in BC cells. Moreover, miR-206 significantly increased the levels of p53 and its acetylated form. CONCLUSION:The upregulation of miR-206 enhanced the efficacy of radiotherapy by promoting apoptosis and reducing cell survival. It also resulted in elevated levels of p53 and its acetylation. Therefore, miR-206 may be considered a promising candidate for radiosensitizing BC cells.

Cancer treatment often relies on radiotherapy, but its efficacy is hampered by limited precision in distinguishing cancerous cells from healthy ones. Quantum dots (QDs), particularly carbon-based (CQDs) and phosphorus-based (BPQDs), have emerged as promising radiosensitizers to improve radiotherapy outcomes. These non-metallic QDs enhance radiosensitivity through mechanisms such as reactive oxygen species (ROS) generation, modulation of cellular pathways, and interference with DNA repair processes. Hybrid systems combining QDs with bacteria, chemotherapeutic agents, and nanoparticles have demonstrated synergistic effects, offering enhanced radiosensitization. This review highlights the unique properties of carbon- and phosphorus-based QDs, their potential in overcoming radiotherapy limitations, and their future integration into multimodal treatment strategies. Despite their promise, challenges related to biosafety, targeting specificity, and regulatory approval remain, requiring further research and development before clinical application.

IntroductionEsophageal squamous cell carcinoma (ESCC) is a prevalent and lethal cancer, with traditional treatments often ineffective. This study investigates the anti-proliferative and anti-metastatic effects of natural compounds Urolithin A (UA) and Urolithin B (UB) on ESCC cell lines KYSE-30 and YM-1.MethodsKYSE-30 and YM-1 ESCC cells were treated with UA and UB, and their viability assays, cell cycle arrest, apoptosis, expressions of mRNA linked to apoptosis and metastasis, generation of reactive oxygen species (ROS), activity of MMP-2 and MMP-9, along with mRNA expressions of MMP-2 and MMP-9, and migration were assessed.ResultsThe results showed that UA (which had lower IC50 than UB) and UB reduced the viability of both KYSE-30 and YM-1 cells. Furthermore, UA and UB exhibited lower toxicity towards normal HFF cells compared to ESCC cells. Both UB and the more effective UA induced apoptosis and caused G2/M cell cycle arrest in KYSE-30 and YM-1 cells. Additionally, UA and UB elevated ROS production and led to a decrease in Bcl-2 expression while increasing the expression of Bax and p21 genes. A decrease in the mRNA expression and enzymatic activity of MMP-2 and MMP-9 was observed following treatment with UA and UB.ConclusionUB and, more potently, UA show the potential to induce apoptosis while reducing metastatic properties and migration of ESCC cells, suggesting them as promising candidates for new anti-ESCC therapies; however, further preclinical and clinical research is needed to fully understand their anti-cancer effects and mechanisms.

Osteosarcoma (OS) is the most common cancerous bone tumor in children and adolescents. By loading combretastatin A4 (CA4) onto the β-cyclodextrin-magnetic-graphene oxide (β-CD-MGO) nanoparticles decorated with folic acid (FA), β-CD-MGO-CA4-FA was created, and apoptotic and anti-metastatic effects on the MG-63 cell line were evaluated. β-CD-MGO-CA4-FA was assessed using DLS, FESEM, FTIR, XRD, and EDX for size distribution, morphology, structure, and elemental composition. MG-63 cells treated with β-CD-MGO-CA4-FA were evaluated through viability assays, cell cycle analysis, apoptosis assays, ROS generation, invasion assays, and migration wound healing. Additionally, mRNA and protein expressions related to apoptosis, metastasis, and MMP-2/MMP-9 activity were evaluated. The study characterizes the β-CD-MGO-CA4-FA nanocomposite, confirming functional groups, morphology, and iron conjugation, with a 41.3

Photodynamic therapy (PDT) is an innovative and minimally invasive approach that has attracted considerable attention and interest in the medical community in recent years. The technique is primarily used to treat tumors and has received official approval for the management of several types of cancer. The process involves the injection of specialized light-sensitive materials into the body. Subsequently, when light of an optimal wavelength (the wavelength at which the photosensitizer is best absorbed and penetrates the tissue) is directed at these materials, it causes the production of reactive oxygen species. These reactive oxygen species play an important role in inducing cellular damage that ultimately leads to the death of cancer cells. Therefore, this treatment modality is based on three fundamental principles. This review comprehensively examines the fundamental principles governing PDT, with a specific focus on photosensitizer design, irradiation parameters, and tumor microenvironment oxygenation. A critical analysis of each component is provided, underscoring their collective importance in optimizing PDT efficacy for oncological applications.

The blood-brain barrier (BBB) presents a major obstacle to effective drug delivery for neurological disorders. Recent advances in perfluorocarbon (PFC) nanotechnologies have shown promise in modulating BBB permeability for improved therapeutic outcomes. This review explores the dual role of PFC-based systems in both enhancing drug delivery and stabilizing the BBB under pathological conditions. Unlike previous reviews that mainly emphasize microbubble-assisted focused ultrasound for BBB opening, this work specifically highlights the unique contributions of PFC nanotechnologies, including their laser- and ultrasound-responsiveness, smaller nanoscale formulations enabling deeper penetration, and their emerging neuroprotective properties. The use of PFC nanoemulsions combined with focused ultrasound (FUS) has demonstrated efficient cellular uptake and targeted drug delivery to brain tumors, while laser-activated PFC nanodroplets and low-boiling-point PFC nanodroplets offer transient BBB disruption via phase transitions and acoustic cavitation. Moreover, PFC derivatives like perfluorooctyl bromide (PFOB) have shown protective effects in models of subarachnoid hemorrhage by reducing BBB permeability and mitigating neuronal apoptosis. Despite these promising findings, challenges remain in optimizing PFC formulations, evaluating long-term safety, and understanding their mechanistic effects on the BBB. Future research should focus on refining these systems through combination strategies and exploring their potential in the treatment of neurodegenerative diseases and cerebrovascular disorders.

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:Drug resistance has been a problem in cancer chemotherapy, which often causes shortterm effectiveness. Further, the literature indicates that telomere G-quadruplex could be a promising anti-cancer target. OBJECTIVE:We synthesized and characterized two new pyrimidine derivatives as ligands for G-quadruplex DNA. METHODS:The interaction of novel non-cationic and cationic pyrimidine derivatives (3a, b) with G-quadruplex DNA (1k8p and 3qsc) was explored by circular dichroism (CD) and ultraviolet-visible spectroscopy and polyacrylamide gel electrophoresis (PAGE) methods. The antiproliferative activity of desired compounds was evaluated by the MTT assay. Apoptosis induction was assessed by Propidium iodide (P.I.) staining and flow cytometry. Computational molecular modeling (CMM) and molecular dynamics simulation (MD) were studied on the complexes of 1k8p and 3qsc with the compounds. The van der Waals, electrostatic, polar solvation, solventaccessible surface area (SASA), and binding energies were calculated and analyzed. RESULTS:The experimental results confirmed that both compounds 3a and 3b interacted with 1k8p and 3qsc and exerted cytotoxic and proapoptotic effects on cancer cells. The number of hydrogen bonds and the RMSD values increased in the presence of the ligands, indicating stronger binding and suggesting increased structural dynamics. The electrostatic contribution to binding energy was higher for the cationic pyrimidine 3b, indicating more negative binding energies. CONCLUSION:Both experimental and MD results confirmed that 3b was more prone to form a complex with DNA G-quadruplex (1k8p and 3qsc), inhibit cell growth, and induce apoptosis, compared to the non-cationic pyrimidine 3a.

Silicon dioxide nanoparticles (SiO2-NPs) can be found in many products, such as composites, paints, ceramics, consumer products, and food additives. We recently demonstrated that via breastfeeding, SiO2-NPs transfer to the offspring’s brain, interfering negatively with hippocampus development. In this work, we evaluated the protective effect of grape seed extract (GSE) against the adverse effects of SiO2-NPs. After delivery, animals were administered 25 mg/kg SiO2-NPs with/without GSE (300 mg/kg) for 20 days (from 2nd to 21st days post-delivery) by gavage. SiO2-NPs increased malondialdehyde concentration and decreased antioxidant activity in the offspring’s hippocampi. The mean number of dark neurons (DNs) was significantly higher in the hippocampi of the SiO2-NPs group, whereas the mean number of DCX + cells was significantly lower than in the control group. The offspring in the SiO2-NPs groups had a weak cognitive performance in adulthood. Interestingly, these adverse effects of SiO2-NPs were alleviated in the GSE-treated groups. Therefore, GSE can attenuate the damaging effects of maternal exposure to SiO2-NPs during lactation.

Objective: The present work examined the anti -metastatic effects of auraptene and their underlying mechanisms of action in U87 Glioblastoma multiforme (GBM) cells. Materials and Methods: To test the hypothesis, cell culture, Matrigel invasion assay, scratch wound healing assay, gelatin zymography assay, qRT-PCR, and western blot experiments were conducted. Results: At sublethal concentrations of 12.5 and 25 mu g/ml, auraptene exhibited a significant reduction in cell invasion and migration of U87 cells, as assessed using scratch wound healing and Transwell tests, respectively. The qRT-PCR and zymography experiments demonstrated a significant decrease in both mRNA expression and activities of MMP-2 and MMP-9 following auraptene treatment. Western blot analysis also showed that MMP2 protein level and phosphorylation of metastasis -related proteins (p-JNK and p-mTOR) decreased in auraptene-treated cells. Molecular docking studies consistently demonstrated that auraptene exhibits a significant affinity towards MMP-2/-9, the ATP binding site of mTOR and JNK1/2/3. Conclusion: Auraptene inhibited the migration and invasion of GBM cells. This inhibitory effect was induced by modulating specific mechanisms, including suppressing MMPs, JNK, and mTOR activities.

The involvement of malfunctioning glutamate systems in various central nervous system (CNS) disorders is widely acknowledged. Urolithin B, known for its neuroprotective and antioxidant properties, has shown potential as a therapeutic agent for these disorders. However, little is known about its protective effects against glutamate-induced toxicity in PC12 cells. Therefore, in this study, for the first time we aimed to investigate the ability of Urolithin B to reduce the cytotoxic effects of glutamate on PC12 cells. Different non-toxic concentrations of urolithin B were applied to PC12 cells for 24 h before exposure to glutamate (10 mM). The cells were then analyzed for cell viability, intracellular reactive oxygen species (ROS), cell cycle arrest, apoptosis, and the expression of Bax and Bcl-2 genes. The results of MTT assay showed that glutamate at a concentration of 10 mM and urolithin B at a concentration of 114 μM can reduce PC12 cell viability by 50

Acute myeloid leukemia is one of the most commonly identified hematological malignancies with poor prognosis. This research was planned to identify the cytotoxic effects of Auraptene on HL60 and U937 cell lines. The cytotoxic effects of Auraptene were measured by AlamarBlue assay (Resazurin) after 24- and 48-h treatments with different doses of Auraptene. The inductive effects of Auraptene on cellular oxidative stress were investigated by determining cellular ROS levels. The cell cycle progression and cell apoptosis were also evaluated by flow cytometry method. Our findings revealed that Auraptene decreased HL60 and U937 cellular proliferation by downregulation of Cyclin D1. Auraptene also induces cellular oxidative stress by upregulation of cellular ROS levels. Auraptene induces cell cycle arrest the early and late phases of apoptosis by upregulation of Bax and p53 proteins. Our data suggest that the anti-tumor function of Auraptene can be mediated by promoting apoptosis and cell cycle arrest and inducing cellular oxidative stress in HL60 and U937 cell lines. These results support that Auraptene may be used as a potent anti-tumor agent against hematologic malignancies in the further studies.