Despite the global coverage of the early detection programs, cervical cancer is still one of the most common causes of death among women worldwide. The integration of Pap test in the healthcare systems worldwide has led to major advances in the diagnosis of premalignant changes in the cervix, although there are limitations regarding the sensitivity of the test. Due to the somewhat lower sensitivity and specificity of the Pap test, the Human Papillomavirus (HPV) (test has been adopted as the first-tier screening method. The further evaluation of the findings is followed by the various complementary techniques and methods to diagnose patients or quantify the risk of developing high-grade cervical intraepithelial lesions. These techniques are increasingly being investigated to provide specific and reliable final diagnosis and instruct the further treatment. This review summarizes the biological basis of p16 and Ki-67 expression, their correlation, and their diagnostic role in the triage of HPV-positive women. The analysis includes results from major clinical trials and meta-analyses, which demonstrate that dual immunostaining of p16/Ki-67 provides higher sensitivity for detecting CIN2+/CIN3+ compared to cytology alone, with an acceptable trade-off in specificity. In conclusion, dual staining represents a reliable complementary tool for the evaluation of abnormal cytological findings, improving early detection of cervical cancer and guiding the appropriate management and treatment of patients.

Current standard treatments for osteosarcoma have not been changed for decades and have limited and variable success. The advancement of precision medicine technologies, along with the drug-repurposing and fast drug-screening methodologies available, has opened new avenues for the development of more effective therapeutic strategies. In this study, we evaluated the effectiveness of halogenated boroxine (HB) and dextran-coated cerium oxide nanoparticles—DexCeNPs (SD2)—in an in vitro osteosarcoma model. Both agents were tested individually and in combination. The research encompassed assessments of treatment-related cytotoxicity and cell viability, oxidative stress, and apoptotic and necrotic responses, as well as the effects on 3D spheroid models. The results demonstrated that the effects of HB and SD2 were strongly influenced by the dose, exposure time, and cell type. Both exhibited distinguished antitumor activity through cytotoxicity and specific reactive oxygen species (ROS) induction. The combined treatment produced modulated responses that were dependent on the treatment ratio and cell line, suggesting potential synergistic or selective interactions. Notably, the outcomes of the analysis conducted in 3D models revealed reduced toxicity toward non-tumor cells. These findings suggest the improved efficacy of HB and SD2 used in combination as a selective and novel antitumor strategy and underscore the need for further mechanistic studies at the transcriptomic and proteomic levels to elucidate the underlying pathways and clarify the mechanisms of action.

Rectal carcinoma (RC) represents approximately 30% of all colorectal carcinomas (CRC) and is considered a distinct clinical entity. Vascular invasion (VI) is recognized as an independent predictor of poor outcomes in RC. In this study, we applied bioinformatics methods to identify gene pathways most likely associated with VI in rectal carcinoma. As ADAMTS8 showed statistically significant negative relations with the VI in RC patients, we further analyzed its top co-dependent genes—DNAL4, EVI2B, PPP1R35, PTGR3, RPL21, SOX4, and ZNF3—for the experimentally proven molecular modulators. We identified a total of 23 compounds from the Comparative Toxicogenomics Database based on previously reported data for all eight target genes. The search was expanded to include additional chemical agents by structure similarity using the PubChem database, which revealed 9661 additional compounds. These were subsequently used for molecular interaction analysis against target proteins co-expressed with, or associated with, ADAMTS8 in RC with VI. Ultimately, we identified four high-affinity compounds—cyanoginosin LR, doxorubicin, benzo[a]pyrene, and dibenzo(a,e)pyrene—that interacted with all target proteins. These compounds show potential for further assessment of their role in modulating processes related to vascular invasion, which is a strong negative predictor of RC outcomes.

Nanotechnology has seen significant growth in the past few decades, with the use of nanomaterials reaching a wide scale. Given that antimicrobial resistance is peaking, nanotechnology holds distinct potential in this area. This review discusses recent applications of metal and metal oxide nanoparticles as antibacterial, antifungal, and antiviral agents, particularly focusing on their topical applications and their role in chronic wound therapy. We explore their use in various forms, including coated, encapsulated, and incorporated in hydrogels or as complexes, proposing them as topical antimicrobials with promising properties. Some studies have shown that metal and metal oxide nanoparticles can exhibit cytotoxic and genotoxic effects, while others have found no such properties. These effects depend on factors such as nanoparticle size, shape, concentration, and other characteristics. It is essential to establish the dose or concentration associated with potential toxic effects and to investigate the severity of these effects to determine a threshold below which metal or metal oxide nanoparticles will not produce negative outcomes. Therefore, further research should focus on safety assessments, ensuring that metal and metal oxide nanoparticles can be safely used as therapeutics in biomedical sciences.

Objective: Iris species are widely used in pharmaceutical and cosmetic applications owing to their high content of bioactive compounds with anti-inflammatory and antimicrobial properties. This study aimed to investigate the potential antibacterial effect of crude extracts (aqueous, 50% and 80% ethanol) of three Iris species ( I. pumila , while I. reichenbachii and I. illyrica are endemic) from Bosnia and Herzegovina against the multiresistant bacterial strain methicillin-resistant Staphylococcus aureus subsp. aureus ATCC 33591 (MRSA strain). Materials and Methods: The antimicrobial compounds in the crude extracts were identified using High-performance liquid chromatography (HPLC), and their effects on the MRSA strain were tested using agar well diffusion and broth microdilution method. The binding affinities were analysed using molecular docking simulations. Results: We identified bioactive targeted compounds in these extracts, mainly flavonoids named isorhamnetin, hesperidin, quercetin, fisetin, genistein, and kaempferol. Antibacterial assays showed that extracts of all three Iris species inhibited MRSA. The binding affinity analysis showed that isorhamnetin and hesperidin had the highest affinity scores, stronger (isorhamnetin) or the same (hesperidin) as the positive control ceftobiprole. Conclusion: This in vitro and in silico study showed that Iris species represent a valuable source of bioactive compounds that can be used against multidrug-resistant strains such as MRSA. The potential use of these agents in multiple drugs is warranted, and further evaluation for human application is needed.

Halogenated boroxine K2[B3O3F4OH] (HB), an inorganic derivative of cyclic anhydride of boronic acid, is patented as a boron-containing compound with potential for the treatment of both benign and malignant skin changes. HB has effectively inhibited the growth of several carcinoma cell lines. Because of the growing interest in autophagy induction as a therapeutic approach in bladder carcinoma (BC), we aimed to assess the effects of HB on metabolic phenotype and autophagy levels in 5637 human bladder carcinoma cells (BC). Cytotoxicity was evaluated using the alamar blue assay, and the degree of autophagy was determined microscopically. Mitochondrial respiration and glycolysis were measured simultaneously. The relative expression of autophagy-related genes BECN1, P62, BCL-2, and DRAM1 was determined by real-time PCR. HB affected cell growth, while starvation significantly increased the level of autophagy in the positive control compared to the basal level of autophagy in the untreated negative control. In HB-treated cultures, the degree of autophagy was higher compared to the basal level, and metabolic phenotypes were altered; both glycolysis and oxidative phosphorylation (OXPHOS) were decreased by HB at 0.2 and 0.4 mg/mL. Gene expression was deregulated towards autophagy induction and expansion. In conclusion, HB disrupted the bioenergetic metabolism and reduced the intracellular survival potential of BC cells. Further molecular studies are needed to confirm these findings and investigate their applicative potential.

Introduction: Breast cancer (BC) is the most common malignancy in the female population globally. Obesity is associated with an increased risk of postmenopausal BC, BC recurrence, and mortality. Fat mass and obesity-associated (FTO) gene polymorphisms have attracted the most attention due to several single-nucleotide polymorphisms (SNPs) that may have an impact on obesity and different types of cancer. The primary goal of our work was to assess the association of the SNP rs17817449 FTO, physical status/metabolic changes, and dietary habits with the occurrence of BC. Methods: We conducted research as a population-genetic study including 93 women with a diagnosis of BC during their lifetime. Genomic DNA was extracted from the swabs of the buccal mucosa. Genotyping was achieved by polymerase chain reaction-restriction fragment length polymorphism. The IBM SPSS Statistics program v. 23.0 was used for statistical analysis. All values of p < 0.05 were considered statistically significant. Results: The risk genotype of the FTO gene (rs17817449) GG was detected in 16 subjects (17.2%), the heterozygous TG in 46 subjects (49.5%), while the normal genotype TT was recorded in 29 subjects (31.2%). We found no statistically significant difference in the body mass index values of the three genotype groups, p = 0.72, χ2 = 2.1 and no significant relationship between the allelic or genotypic frequencies of the rs17817449 FTO gene polymorphism and other variables examined in our study. Analysis of the distribution of hereditary diseases in the family according to the molecular subtype of BC showed statistically significant p-values, p = 0.02. Conclusion: While previous research has suggested a potential link between FTO gene polymorphism, obesity, and BC, our study did not find a statistically significant association between the aforementioned variables. Future studies with a larger number of subjects in different populations should confirm the role of the FTO genotype in the risk of BC.