International Journal of Molecular and Cellular Medicine最新文献

Liver cancer treatment faces significant obstacles such as resistance, recurrence, metastasis, and toxicity to healthy cells. Biometallic nanoparticles (NPs) have emerged as a promising approach to address these challenges. In this study, copper oxide-silver (Ag-doped CuO) NPs were prepared using a reduction method with Ephedra intermedia extract. The physicochemical properties of the NPs were evaluated using various techniques such as Field emission scanning electron microscopy (FESEM), Transmission Electron Microscope (TEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR). Additionally, this study has evaluated nitric oxide levels (NO), reactive oxygen species (ROS) production, Bax, Bcl2, P53, and Caspase3 genes expression, as well as cell viability within 24 hours in liver cancer cell line HepG2. FESEM and TEM imaging confirmed the nanostructural nature of the synthesized particles with sizes ranging from 31.27 to 88.98 nanometers. XRD analysis confirmed the crystal structure of the NPs. Comparative analysis showed that the IC₅₀ values of the Ag-doped CuO NPs were significantly lower than that of the plant extracts. Molecular studies showed significantly increased expression of Bax, Caspase3, and P53 genes, inducing apoptosis in cancer cells, and downregulation of Bcl2 as a pro-metastasis gene. Additionally, the presence of Ag-doped CuO NPs significantly increased NO activity enzyme and ROS generation compared to the plant extract. The biosynthesized Ag-doped CuO NPs demonstrated the ability to induce apoptosis, increase ROS production, and enhance NO enzyme activity in HepG2 cancer cells, suggesting their potential as a therapeutic agent for liver cancer.

Esophageal cancer presents a challenge in gastroenterology and traditional chemotherapy and radiation therapy have less therapeutic activity with severe side effects. Thus, there is need for effective and safer alternatives. Probiotics, particularly Lactobacillus plantarum (L. plantarum) and its bacteriocins, might prevent or treat esophageal tumors. We aimed to investigate the use of L. plantarum and its bacteriocin as esophageal cancer therapy. First, we obtained 100 isolates of Lactobacillus spp. from dairy product samples. They screened for bacteriocin production and identified by PCR and gel electrophoresis for 16S ribosomal RNA gene. Bacteriocin was partially purified and tested against two different pathogens. Both L. plantarum and its bacteriocin were examined for cytotoxicity in vitro against esophageal cancer cell line (SK-GT4) and normal rat embryo fibroblast (REF) cells by MTT assay. Apoptosis was determined using an acridine orange /propidium iodide assay. The results showed that the isolate gives a high bacteriocin production about (2000AU/ml). In addition to antimicrobial activity, there was significant anticancer activity. L. plantarum had an IC₅₀ of 51.01 CFU/ml and bacteriocin IC₅₀ of 281.9 AU/ml against cancer cells. Both showed no cytotoxicity towards normal REF cells. Furthermore, there was a significant increase in apoptosis induction and in caspase-3 activity in cancer cells treated with L. plantarum and bacteriocin compared to untreated cells. In conclusion, L. plantarum and its bacteriocin show potent killing effect against esophageal cancer cells with no effect against normal cells indicating safety and selectivity with activation of apoptosis via caspase-3 induction suggesting potential clinical advantage.

Glioblastoma (GBM) is the most aggressive and lethal brain tumor. Artificial neural networks (ANNs) have the potential to make accurate predictions and improve decision making. The aim of this study was to create an ANN model to predict 15-month survival in GBM patients according to gene expression databases. Genomic data of GBM were downloaded from the CGGA, TCGA, MYO, and CPTAC. Logistic regression (LR) and ANN model were used. Age, gender, IDH wild-type/mutant and the 31 most important genes from our previous study, were determined as input factors for the established ANN model. 15-month survival time was used to evaluate the results. The normalized importance scores of each covariate were calculated using the selected ANN model. The area under a receiver operating characteristic (ROC) curve (AUC), Hosmer-Lemeshow (H-L) statistic and accuracy of prediction were measured to evaluate the two models. SPSS 26 was utilized. A total of 551 patients (61% male, mean age 55.5 ± 13.3 years) patients were divided into training, testing, and validation datasets of 441, 55 and 55 patients, respectively. The main candidate genes found were: FN1, ICAM1, MYD88, IL10, and CCL2 with the ANN model; and MMP9, MYD88, and CDK4 with LR model. The AUCs were 0.71 for the LR and 0.81 for the ANN analysis. Compared to the LR model, the ANN model showed better results: Accuracy rate, 83.3 %; H-L statistic, 6.5 %; and AUC, 0.81 % of patients. The findings show that ANNs can accurately predict the 15-month survival in GBM patients and contribute to precise medical treatment.

It is expected that the amount of recently diagnosed colon cancer cases will increase to around 3.2 million yearly until 2040. Although early diagnostic procedures and management approaches have been improved, colorectal cancer (CRC) treatment remains challenging. There is an urgent need to discover new therapeutic agents to enhance therapeutic strategies. Ferroptosis is distinguished as a mode of regulated cell death considered by iron-dependent lipid peroxidation. Contemporary investigations suggest that induction of ferroptosis in CRC can effectively target neoplastic cells that are resistant to alternative forms of cell death. This review has summarized recent scientific work on the implications of ferroptosis in CRC treatment and highlights its underlying molecular and biological mechanisms. While investigating its therapeutic potential, it shows the importance of diverse modulators of ferroptosis, including the 7-membered solute carrier family 11 or xCT (SLC7A11), reactive oxygen species (ROS), glutathione (GSH), and iron in the context of CRC. Recent research has identified specific pathways and compounds that can induce ferroptosis in CRC, such as apatinib and elesclimol, which are involved in pivotal signaling cascades. Attenuation of proteins such as splicing factor, arginine/serine 9 (SFRS9), and Tp53-induced glycolysis and apoptosis regulator (TIGAR) may increase the sensitivity of CRC cells to ferroptosis, thus suggesting promising therapeutic avenues. Compounds including IMCA and β-elemene have shown efficacy in inducing ferroptosis while minimizing toxicity to normal tissues, thereby demonstrating their potential as therapeutic agents for CRC. Participating ferroptosis stimulator drugs with current treatment regimens, such as cetuximab and aspirin, may offer better treatment outcomes for CRC patients, especially those presenting resistance to conventional therapies.

Chronic lymphocytic leukemia (CLL) is the most prevalent hematological cancer, with various medical interventions. In the recent decade, cold physical plasma has become an interesting agent for future cancer therapy. The goal of this study was to see whether cold physical plasma or cold physical plasma-treated liquid (PTL) affected integrin beta 3 (ITGB3) expression, which is hypothesized to mediate an interaction between cancer stem cells and the bone marrow microenvironment, in CLL patients' blood cells. The metabolic activity, cell death pattern, lipid oxidation and ITGB3 gene expression of these treatments was evaluated. Both direct cold physical plasma and PTL exposure enhanced lipid peroxidation in cells of CLL patients, but to a lesser extent in healthy participants. Furthermore, following 48h of cold physical plasma or PTL exposure, the metabolic activity of leukocytes was preferentially reduced in CLL patient leukocytes. In addition, cold physical plasma and PTL treatment elevated ITGB3 mRNA expression in CLL patients' leukocytes compared to untreated and healthy controls. Collectively, our study suggests selective effects of direct cold physical plasma and PTL exposure on blood leukocytes from leukemia patients, but further and more detailed studies are needed to provide additional rationales for such treatment options as future therapy.

Breast cancer, characterized by genetic diversity and molecular subtypes, presents significant treatment challenges, especially in human epidermal growth factor receptor type 2 (HER2)-positive cases, which are associated with poor prognosis. Metformin, widely known for its antidiabetic effects, has emerged as a promising candidate for cancer therapy. This study investigates the effect of metformin on miR-125a promoter methylation and its subsequent impact on the HER2 signaling pathway in HER2-positive breast cancer cells (SK-BR3). SK-BR3 cells were cultured and treated with various concentrations of metformin to assess its effects on cell viability, DNA methylation, HER2, and DNA Methyltransferase 1 (DNMT1) expression. Molecular analyses focus on the miR-125a signaling pathway modulation, DNA methylation, mRNA expression of DNMT1, and protein level of HER2. Research showed a dose-dependent reduction in cell viability, with IC50 values from 65 mM at 48 hours to 35 mM at 72 hours. Metformin treatment led to demethylation of the miR-125a promoter, which increased miR-125a expression and subsequently reduced HER2 levels. This suggests that metformin exerts its anticancer effects partly by regulation of the miR-125a-HER2 axis. Additionally, metformin inhibited vimentin expression, indicating its potential to interfere with epithelial-mesenchymal transition (EMT) processes. Metformin may serve as a targeted therapeutic agent in HER2-positive breast cancer by modulating the miR-125a-HER2 axis and influencing on the epigenetic and EMT regulation. Further research is warranted to elucidate the therapeutic potential of metformin through these mechanisms.

The develop of new anticancer drug continues worldwide and one of the new therapeutic targets to reach it is Otubain 1 (OTUB1), since OTUB1 has functions related to prognosis in a variety of tumors and is strongly related to tumor proliferation, migration, and apoptosis by their functions on deubiquitinating. This study uses OTUB1´s active site to develop a specific pharmacological treatment to regulate the OTUB1 functions. The aim of this research was to evaluate the effects of ten compounds (OT1 - OT10), that previously were selected by molecular docking to develop a new anticancer drug to decrease the OTUB1 functions in the cancer processes. We evaluated the cytotoxic effect of OT1 - OT10 compounds on MCF-7, BT474 and MDA-MB 231 cells by MTT assay, and we determined characteristics of apoptosis by western blot analysis. Then, the best compound (OT5) was analyzed by molecular docking, molecular dynamics and theoretical toxicity for describing the interactions of OT5 compound with the OTUB1´s active site. We proposed that the OT5 compound has a high probability to be selective against OTUB1, with an apoptosis (regulating caspase-8) and cytotoxic effect on some cancer lines; IC50 for MCF-7: 97 µM and MDA-MB 231:147 µM, as well as we described that this compound could have specific interactions in the catalytic domain of OTUB1, modifying this protein's activity, decreasing the OTUB1 functions, and probably safe for humans. These results show the high potential of this compound for promoting the development of this compound as a new drug against cancer.

Colorectal cancer is one of the most serious malignancies affecting humans. In this study, Streptomyces bioactive chemicals extracted from soil were analyzed for their anti-colorectal-cancer and antibacterial properties. A total of 100 soil samples were collected from Kerman-Iran, incubated in SCA media and the antimicrobial properties were tested using the cross-streak method. Three strains were cultured in ISP4 medium to obtain secondary bioactive compounds. After studying the effects of the bioactive compounds on the HT29 and human foreskin fibroblast (HFF) cell lines, the expression of the p53, p21, BAX, BCL2, Casp3 and Casp8 genes was analyzed by real-time PCR and flow cytometry to detect the presence of apoptosis.The isolates show high degree of identification with Streptomyces rochei, Streptomyces fungicidicus and Streptomyces maritimus due to 16SrDNA sequence homology. Compared to HT-29 cells, Streptomyces extracts had lower cytotoxicity against normal cells (SI=5.88), followed by HFF (SI=4.14). The cell lines demonstrated a dose-dependent significant increase in DNA fragmentation, an increase in the proportion of cells in sub-G1 phase and caused G2/M cell cycle arrest in HT-29 and HFF cells.The bacterial extracts obtained displayed strong antibacterial properties and inhibited the proliferation of HT-29 and HFF cell lines. The treated cells exhibited morphological changes caused by the activation of caspase and p53/p21 proteins. This confirms that Streptomyces-induced apoptosis is mediated by the activation of p21/p53. Anti-apoptotic Bcl-2 gene expression was downregulated by treatment with the extracts. Further studies are needed to understand the antimicrobial properties of Streptomyces.

Coronary Slow Flow (CSF) is observed in individuals who experience delayed blood supply in the coronary arteries. Inflammation and endothelial dysfunction may play a role in the etiology and development of CSF. The current investigation aimed to compare the expression of specific long noncoding RNAs (lncRNAs) associated with endothelial dysfunction and inflammation in CSF patients. This case‒control study enrolled 72 CSF patients and 71 healthy individuals. Blood samples were collected, and serum marker levels were measured. The expression levels of lncRNAs ANRIL, MALAT1, and LINC00305 in peripheral blood mononuclear cells (PBMCs) were assessed using real-time Polymerase Chain Reaction (PCR). All statistical analyses were performed using SPSS 22, with the significance level set at P < 0.05. The study revealed that the relative expression of MALAT1 and LINC00305 was significantly lower in the CSF group (p < 0.01), whereas ANRIL was expressed at higher levels (p < 0.0001). The areas under the ROC curves (AUCs) for MALAT1, LINC00305, and ANRIL were 0.64, 0.66, and 0.75, respectively. Notably, the expression level of LINC00305 exhibited an inverse correlation with CSF incidence (OR: 0.83, p: 0.008) in contrast to that of ANRIL (OR: 1.43, p < 0.0001). Additionally, compared to those in the control group, the average BMI, WBC, RBC, Hb, LDH, LDL, FBS, and percentage of neutrophils in the CSF group were significantly greater (p< 0.05). lncRNA ANRIL is upregulated in CSF patients, whereas MALAT1 and LINC00305 are downregulated. Dysregulation of ANRIL, MALAT1, and LINC00305 may serve as diagnostic and predictive factors for CSF leakage.

Rosemary is an aromatic plant with ancient and modern applications as a spice and herbal remedy. Due to the strong antioxidant potential of rosemary, the present study investigated the anti-proliferative and pro-apoptotic characteristics of rosemary on luminal A and triple-negative breast cancer cells. The effect of rosemary extract on the WNT10B and β-Catenin genes was also evaluated. The WNT10B and β-Catenin expression were measured by real-time PCR. The outcomes of the MTT assay and AnnexinV/PI flow cytometry assay showed that exposure of MCF-7 and MDA-MB-231 cells to rosemary reduced cell viability in a dose-time-dependent routine and promoted apoptosis in breast cancer cells. It was revealed that the extract could exert cytotoxic and apoptotic effects by downregulation of WNT10B and β-Catenin. Our results suggest rosemary as a promising complementary herbal medicine for breast cancers, without the adverse effects of chemotherapy drugs.