Cell Biochemistry and Biophysics最新文献

Hepatocellular carcinoma (HCC), the third leading cause of global cancer deaths, has a high unmet clinical need due to limited therapeutic efficacy. Immune escape mechanisms in the tumor microenvironment further complicate treatment. Advances in bioinformatics and machine learning offer potential for identifying novel biomarkers and therapeutic targets. This study aimed to identify immune-related prognostic biomarkers for HCC using integrative bioinformatics and machine learning, and validate their functional roles in tumor progression and immune escape. mRNA data from TCGA and GEO databases were analyzed to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) and three machine learning models (Random Forest, Boruta, XGBoost) were applied to screen key genes. Candidate genes were validated using qRT-PCR, Western blot, and functional assays (CCK8, colony formation, LDH, flow cytometry) in HCC tissues and cell lines. Immune correlations were assessed via CIBERSORT, and TNF-α/NF-κB pathway involvement was investigated. Total 26 genes were screened as HCC biomarkers through machine learning analysis. DCAF13 emerging as an independent prognostic factor. It was overexpressed in HCC tissues and cells, correlating with poor survival. Sh-DCAF13 suppressed proliferation, reduced PD-L1 expression, enhanced CD8 + T cell cytotoxicity, and decreased T cell apoptosis, inhibiting immune escape. TNF-α overexpression reversed these effects by restoring NF-κB activation. DCAF13 is a promising therapeutic target for HCC. Its role in modulating immune escape via the NF-κB pathway highlights potential strategies for personalized immunotherapy. Integrating machine learning with experimental validation provides a robust framework for biomarker discovery in oncology.

Chemotherapy resistance is a major obstacle in cancer; thus, the development of new anticancer agents is being studied with great importance. Schiff bases containing an azomethine group have been widely used in various pharmaceutical applications. Here, five Schiff base derivatives of 2-hydroxybenzaldehyde (8S1-8S5) were synthesized and characterized. Their cytotoxicity was screened against six cancerous and two normal cell lines using a neutral red uptake assay. The apoptotic mechanism of the compound 8S3 in MCF-7 cells was evaluated through a combination of cell cycle analysis, measurement of mitochondrial membrane potential, reactive oxygen species levels, caspase activity, analysis of gene expression in the mitogen-activated protein kinase (MAPK) signalling pathway, and in silico analysis studies. Treatment of the cells with 8S3 resulted in an increase in sub-G0/G1 populations and MMP disruption. The expressions of 30 genes involved in MAPK signalling were upregulated, while 10 genes were downregulated in these cells. This transcriptional profile supports a MAPK-mediated apoptotic response and highlights 8S3's potential to overcome chemoresistance by disrupting key survival MAPK signalling pathways. 8S3 might induces apoptosis through a mechanism involving modulation of MAPK pathway and mitochondrial dysfunction, in a ROS-independent manner. Results highlight 8S3's potential as a candidate for further development of anti-cancer drugs in cancer therapy.

The increase in cancer incidence and mortality demonstrates the need for more effective anti-tumor therapies. Targeted therapies, such as cancer testicular antigens (CTAs), are promising as they are expressed in tumor cells but not in normal cells. TFDP3, a CTA expressed in cancers such as triple-negative breast cancer, prostate cancer, childhood T-cell lymphoblastic leukemia, and hepatocellular carcinoma, was chosen as a target for vaccine development. This study aimed to predict a multi-epitope vaccine based on TFDP3 using immunoinformatics tools to identify antigenic epitopes that interact with B lymphocytes, CD4+T lymphocytes, and CD8+T lymphocytes. Three epitopes from each lymphocyte type were selected, considering factors such as antigenicity, allergenicity, toxicity, IFN-γ induction, and population coverage. The vaccine also included adjuvants and ligands that ensure the stability and proper processing of the epitopes. The in-silico analysis revealed that the vaccine has favorable physicochemical properties, low homology with human proteins, and interactions with Toll-like receptors, ensuring stability. The population coverage world of the MHC class I and II epitopes were 93.55%. Additionally, the vaccine can be cloned and induce a robust immune response after three administrations. Despite the promising results, immunotherapy still faces challenges, such as tumor heterogeneity and immune evasion. In vitro and in vivo studies are necessary to assess the vaccine's efficacy and safety for future cancer treatments that express TFDP3.

Resistance to chemotherapy remains a major obstacle in effective cancer treatment. To address this challenge, we developed multifunctional Fe₃O₄@SiO₂(FITC)-BTN/FA/3AB nanoparticles aimed at selectively enhancing the therapeutic efficacy of 3-aminobenzamide (3AB) while minimizing systemic toxicity, particularly when combined with low-dose cisplatin chemotherapy. In this study, we demonstrate that these nanoparticles not only exhibit potent cytotoxic effects against lung adenocarcinoma cells but also show significant therapeutic potential in human cervical adenocarcinoma models. We systematically evaluated their performance through cellular uptake assay, viability assay, apoptosis analysis, single-cell colony formation assay, mitochondrial membrane potential (MMP) assay, and quantitative PCR (qPCR). Our findings reveal that the nanoparticle formulation efficiently facilitates the intracellular delivery of 3AB, leading to robust inhibition of tumor cell proliferation and migration. Overall, the Fe₃O₄@SiO₂(FITC)-BTN/FA/3AB nanoparticle system represents a promising platform for intratumoral therapy, offering a targeted strategy to potentiate the efficacy of PARP1 inhibition in DNA repair for cervical cancer treatment.

Gentamicin (GM) is an antibiotic, and its uncontrolled use is nephrotoxic. Renal proximal convoluted tubules are the major GM targets. Nephrotoxicity in rats was induced by gentamicin, and the protective effects using pomegranate extract were monitored for 15 days. Thirty male Wistar rats were divided into five groups: control, PG group (ingested pomegranate fruit extract, PG), GM group (80 mg/kg/day gentamicin) and combined treatment PG-GM and GM-PG. The treatment had been applied for two weeks before hematological and biochemical parameters, as well as the particular markers of nephrotoxicity, were analyzed. GM alone caused lymphocytopenia, and granulopenia, hyperbilirubinemia, uricemia, hyperglycemia and high enzyme activities. Therapeutic groups (GM + PG) did not show complete nephroprotection; recovery depended on the period of ingestion, before or after GM administration. Hypobilirubinemia was noted in the GM-PG group. Lactate dehydrogenase (LDH) as an oxidative stress biomarker showed high levels in all treatment groups. PM extract fruit alone can have an immunosuppressive effect, increase the number of platelets, and lower the triglyceride values. The preventive use of PG as a dietary product has certain health benefits, but the therapeutic effect in GM-induced nephrotoxicity is moderate. Pomegranate fruit can normalize altered values of hematological and biochemical parameters, depending on the dose and exposure. Simultaneously, excessive use can result in side effects.

The aim of the study was to examine how the administration of uridine influences the mitochondrial function in hepatocytes in a rat model of hyperthyroidism (HT) induced by thyroxine treatment. Excess thyroid hormones (TH) increased the mitochondrial oxygen consumption, enhanced biogenesis, and altered the expression of proteins regulating the mitochondrial fusion and fission. Hyperthyroid rats had a mixed population of mitochondria, including swollen and damaged organelles. Although uridine did not affect the level of serum TH, it restored the normal body weight. The administration of uridine used for therapeutic purposes improved the main parameters of respiration and oxidative phosphorylation, prevented destructive changes in the morphology of liver mitochondria, and influenced the biogenesis and dynamics of these organelles. Overall, the results obtained indicate that uridine has a protective effect against functional and some structural destructions in rat liver mitochondria induced by HT.