Future trends and emerging issues for nanodelivery systems in oral and oropharyngeal cancer

Alexandra Iulia Irimie,1 Laura Sonea,2 Ancuta Jurj,3 Nikolay Mehterov,4,5 Alina Andreea Zimta,2,3 Liviuta Budisan,3 Cornelia Braicu,3 Ioana Berindan-Neagoe2,3,6 1Department of Prosthodontics and Dental Materials, Faculty of Dental Medicine, 2MedFuture Research Center for Advanced Medicine, 3Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 4Department of Medical Biology, Medical University of Plovdiv, 5Technological Center for Emergency Medicine, Plovdiv, Bulgaria; 6Department of Functional Genomics and Experimental Pathology, Ion Chiricuta Oncology Institute, Cluj-Napoca, Romania Abstract: Oral cancer is a prevalent cancer type on a global scale, whose traditional treatment strategies have several drawbacks that could in the near future be overcome through the development of novel therapeutic and prognostic strategies. Nanotechnology provides an alternative to traditional therapy that leads to enhanced efficiency and less toxicity. Various nanosystems have been developed for the treatment of oral cancer, including polymeric, metallic, and lipid-based formulations that incorporate chemotherapeutics, natural compounds, siRNA, or other molecules. This review summarizes the main benefits of using these nanosystems, in parallel with a particular focus on the issues encountered in medical practice. These novel strategies have provided encouraging results in both in vitro and in vivo studies, but few have entered clinical trials. The use of nanosystems in oral cancer has the potential of becoming a valid therapeutic option for patients suffering from this malignancy, considering that clinical trials have already been completed and others are currently being developed. Keywords: oral cancer, nanoparticle, lipidic nanosystems, polymeric micelles, dendrimer

Double gene siRNA knockdown of mutant p53 and TNF induces apoptosis in triple-negative breast cancer cells

Valentina Pileczki,1,2 Laura Pop,1 Cornelia Braicu,1 Livia Budisan,1 Gabriela Bolba Morar,3 Paloma del C Monroig-Bosque,4 Robert V Sandulescu,2 Ioana Berindan-Neagoe1,5,6 1The Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2Department of Analytical Chemistry, Faculty of Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy, 3Department of Senology, the Oncology Institute “Prof Dr Ion Chiricuta”, Cluj-Napoca, Romania; 4University of Puerto Rico School of Medicine, San Juan, Puerto Rico; 5MedFuture Research Center for Advanced Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 6Department of Functional Genomics and Experimental Pathology, the Oncology Institute “Prof Dr Ion Chiricuta”, Cluj-Napoca, Romania Abstract: Apoptosis is the major downregulated pathway in cancer. Simultaneous inhibition using specific small interfering RNA (siRNA) of two key player genes, p53 and TNF, is an interesting and feasible strategy when it comes to investigating various molecular pathways and biological processes in triple-negative breast cancer (TNBC), which is one of the most aggressive and therapeutically unresponsive forms of breast cancers. Our present research focuses on evaluating the impact of double p53-siRNA and TNF-siRNA knockdown at a cellular level, and also evaluating cell proliferation, apoptosis, induction of autophagy, and gene expression by using reverse transcription polymerase chain reaction array approaches. Simultaneous inhibition of p53 and TNF in Hs578T TNBC human cell line revealed a panel of up- and downregulated genes involved in apoptosis. Furthermore, the effects of double gene knockdown were validated in a second TNBC cell line, MDA-MB-231, by using reverse transcription polymerase chain reaction TaqMan assay. All our findings help in understanding the functional mechanisms of extrinsic apoptosis, cell signaling pathways, and the mechanisms involved in tumor cell survival, growth, and death in TNBC. Keywords: apoptosis, double gene silencing, mut-p53, TNF, TNB

Relationship between Adipokines and Cardiovascular Ultrasound Parameters in Metabolic-Dysfunction-Associated Fatty Liver Disease

(1) Background: The role of adipokines such as adiponectin and visfatin in metabolic-dysfunction-associated fatty liver disease (MAFLD) and cardiovascular disease remains unclear. Therefore, we aim to assess serum adiponectin and visfatin levels in MAFLD patients and associated cardiovascular parameters. (2) Methods: A cross-sectional study involving 80 participants (40 MAFLD patients, 40 controls), recruited between January and September 2020, was conducted, using both hepatic ultrasonography and SteatoTestTM to evaluate hepatic steatosis. Echocardiographic and Doppler parameters were assessed. Serum adipokines were measured using ELISA kits. (3) Results: Adiponectin and visfatin levels were not significantly different in MAFLD vs. controls. Visfatin was associated with mean carotid intima-media thickness (p-value = 0.047), while adiponectin was associated with left ventricular ejection fraction (LVEF) (p-value = 0.039) and E/A ratio (p-value = 0.002) in controls. The association between adiponectin and E/A ratio was significant in the univariate analysis at 95% CI (0.0049–0.1331, p-value = 0.035), but lost significance after the multivariate analysis. Although LVEF was not associated with adiponectin in the univariate analysis, significant values were observed after the multivariate analysis (95% CI (−1.83–−0.22, p-value = 0.015)). (4) Conclusions: No significant difference in serum adiponectin and visfatin levels in MAFLD patients vs. controls was found. Interestingly, although adiponectin levels were not associated with LVEF in the univariate analysis, a significant inversely proportional association was observed after the multivariate analysis