Giorgos Theocharous

In recent years, remarkable progress in nanomedicine has been achieved, leading to the development of several nanocarriers which aim to enhance the therapeutic efficacy in cancer treatment. Owing to their high versatility and highly tunable physicochemical properties, alumina (Al₂O₃) and silica (SiO₂) substrates represent promising and innovative nanoplatforms that are widely used in biomedical applications, such as drug-delivery, diagnosis, and biosensing in cancer. In particular, such platforms possess multiple advantageous properties, including mechanical stability, high loading capacity, tunable porosity, excellent biocompatibility, and in vitro and in vivo low toxicity. In this review article, we discuss their emerging role as biosensing platforms and drug delivery systems in oncology. As such, we describe how these substrates enable the incorporation of antibodies against various cancer biomarkers [e.g., cancer antigen 15-3 (CA15-3), serum amyloid A1 (SAA1), epithelial cell adhesion molecule (EpCAM), or human epidermal growth factor receptor 2 (HER2)] for the detection of multiple malignancies. Furthermore, we highlight the development of highly promising alumina- and silica-based platforms for drug delivery (e.g., chemotherapeutics, photosensitizers, or gene delivery agents) in cancer. Ultimately, by providing a comprehensive overview alongside a critical analysis, we demonstrate that such nanostructures represent promising platforms for potential clinical translation in cancer medicine, helping to mitigate the limitations of conventional cancer therapies.

Atherosclerosis, a major contributor to vascular damage and plaque formation, is brought on by cellular senescence and chronic inflammation. A crucial matter that emerges is the classification of the disease in order to understand the pathogenic mechanisms before treatment. Given that oxidative stress, DNA damage, and inflammation contribute to cellular senescence, an increase in pro-inflammatory factors is detected in the atherosclerotic plaque, which exacerbates its instability while impeding vascular repair. This study emphasizes the importance of pathways such as Nrf2, ICAM-1, and p38 MAPK/p16^INK4A in the development of atherosclerosis. It also underscores the potential of senescence-targeting interventions to complement the conventional treatments for atherosclerosis. The study promotes using senolytic approaches that may serve as effective adjuncts to conventional pharmacological treatments for atherosclerosis. Particularly, quercetin, a flavonoid, demonstrates a potential action as senolytic agent by mitigating macrophage senescence, improving lipid profiles, and reducing plaque size of up to 56% in experimental models. This review article advocates for integrating senolytic approaches, including nutraceuticals like quercetin and combination therapies, to improve cardiovascular health and age-related vascular disorders.

Background and Objectives: The presence and contribution of senescent cells in premalignant lesions is well documented, but not in germ cell neoplasia in situ. The purpose of this study is to identify the presence of senescent cells in pre-malignant testicular conditions and in different histological types of testicular cancer. Materials and Methods: Thirty patients who underwent orchiectomy due to testicular tumors were included. Formalin-fixed paraffin-embedded (FFPE) testicular tissue for each patient was available. Sections from these specimens were examined by immunohistochemical analysis with the following markers: GL13 for cellular senescence, p21^WAF1/Cip1 for cell cycle arrest, and Ki67 for cell proliferation. Results: Thirteen (43.3%) suffered from seminoma with a mean total proportion of GCNIS senescence of 20.81 ± 6.81%. In the group of embryonal testicular tumors, nine (30%) patients were included, with an average rate of 6.64 ± 5.42% of senescent cells in GCNIS. One (3.3%) patient suffered from chondrosarcoma in which 7.9% of GL13+ cells were detected in GCNIS. Four (13.4%) patients suffered from teratoma and three (10%) from yolk sac tumors, while GCNIS senescence was detected in a range of 4.43 ± 1.78% and 3.76 ± 1.37%, respectively. Conclusions: Cellular senescence was detected in both germ cell neoplasia in situ and testicular cancer, but was more prevalent within the premalignant lesions.

Purpose: The aim of this experimental study is to investigate the correlation between the presence of senescent cells and the tumor size, the lymphovascular invasion (LVI), the invasion of rete testis (RTI), the preoperative tumor markers or pathological stage in patients who underwent orchiectomy for malignant purposes. Methods: This experimental study included patients with a history of radical orchiectomy performed from January 2011 to January 2019. The testicular tissue specimens underwent an immunohistopathological process for the detection of the presence of cellular senescence. Besides, the tumor size, the histopathological type, the pathological stage of the tumor and the presence of Lymphovascular (LVI) or rete testis (RTI) invasions were also recorded. Additionally, the preoperative serum levels of alpha-fetoprotein, beta-human chorionic gonadotropin and lactate dehydrogenase were recorded. After the completion of immunohistochemical analysis, the rate of senescent cells in each specimen was also recorded. Results: The mean senescent cell rate was estimated to be 14.11 ± 11.32% and 15.46 ± 10.58% in patients with presence of LVI or absence of LVI, respectively (p = 0.46). The mean senescent cell rate was calculated at 18.13±12.26% and 12.56 ± 9.38% (p = 0.096) in patients with presence of RTI or absence of RTI, respectively. The mean senescent cell rate in the pT1 group was calculated at 14.58 ± 9.82%, while in T2 and T3 groups the mean senescent cell rate was estimated to be 15.22 ± 12.03% and 15.35 ± 14.21%, respectively (p = 0.98). A statistically significant correlation was detected between the senescence rate and the tumor size (Pearson score 0.40, p = 0.027) and between the rate of senescent cells and the preoperative level of lactate dehydrogenase (LDH) (Pearson score -0.53, p = 0.002). Conclusions: The presence of cellular senescence was correlated with the extent of the testicular tumor in terms of tumor size as well as the preoperative level of the LDH serum marker.

The wide array of structures and characteristics found in ZnO-based nanostructures offers them a versatile range of uses. Over the past decade, significant attention has been drawn to the possible applications of these materials in the biomedical field, owing to their distinctive electronic, optical, catalytic, and antimicrobial attributes, alongside their exceptional biocompatibility and surface chemistry. With environmental degradation and an aging population contributing to escalating healthcare needs and costs, particularly in developing nations, there’s a growing demand for more effective and affordable biomedical devices with innovative functionalities. This review delves into particular essential facets of different synthetic approaches (chemical and green) that contribute to the production of effective multifunctional nano-ZnO particles for biomedical applications. Outlining the conjugation of ZnO nanoparticles highlights the enhancement of biomedical capacity while lowering toxicity. Additionally, recent progress in the study of ZnO-based nano-biomaterials tailored for biomedical purposes is explored, including biosensing, bioimaging, tissue regeneration, drug delivery, as well as vaccines and immunotherapy. The final section focuses on nano-ZnO particles’ toxicity mechanism with special emphasis to their neurotoxic potential, as well as the primary toxicity pathways, providing an overall review of the up-to-date development and future perspectives of nano-ZnO particles in the biomedicine field.

The currently available anti-cancer therapies, such as gamma-radiation and chemotherapeutic agents, induce cell death and cellular senescence not only in cancer cells but also in the adjacent normal tissue. New anti-tumor approaches focus on limiting the side effects on normal cells. In this frame, the potential anti-tumor properties of Pulsed Electromagnetic Fields (PEMFs) through the irradiation of breast cancer epithelial cells (MCF-7 and MDA-MB-231) and normal fibroblasts (FF95) were investigated. PEMFs had a frequency of 8 Hz, full-square wave type and magnetic flux density of 0.011 T and were applied twice daily for 5 days. The data collected showcase that PEMF application decreases the proliferation rate and viability of breast cancer cells while having the opposite effect on normal fibroblasts. Moreover, PEMF irradiation induces cell death and cellular senescence only in breast cancer cells without any effect in the non-cancerous cells. These findings suggest PEMF irradiation as a novel, non-invasive anti-cancer strategy that, when combined with senolytic drugs, may eliminate both cancer and the remaining senescent cells, while simultaneously avoiding the side effects of the current treatments.

The currently available anti-cancer therapies, such as gamma-radiation and chemotherapeutic agents, induce cell death and cellular senescence not only in cancer cells but also in the adjacent normal tissue. New anti-tumor approaches focus on limiting the side effects on normal cells. In this frame, the potential anti-tumor properties of Pulsed Electromagnetic Fields (PEMFs) through irradiation of breast cancer epithelial cells (MCF-7 and MDA-MB-231) and normal fibroblasts (FF95) were investigated. PEMFs had a frequency of 8 Hz, full-square wave type, magnetic flux density of 0.011 T and applied twice daily for 5 days. Data collected showcases that PEMF application decreases the proliferation rate and viability of breast cancer cells while having the opposite effect on normal fibroblasts. Moreover, PEMF irradiation induced cell death and cellular senescence only in breast cancer cells without any effect in the non-cancerous cells. These findings suggest PEMF irradiation as a novel, non-invasive anti-cancer strategy in combination with senolytic drugs, to eliminate both cancer and the remaining senescent cells while simultaneously avoiding the side effects of the current treatments.

Endothelial glycocalyx (EG) derangement has been associated with cardiovascular disease (CVD). Studies on EG integrity among people living with HIV (PLWH), are lacking. We conducted a prospective cohort study among treatment-naïve PLWH who received emtricitabine/tenofovir alafenamide, combined with either an integrase strand transfer inhibitor (INSTI, dolutegravir, raltegravir or elvitegravir/cobicistat), or a protease inhibitor (PI, darunavir/cobicistat). We assessed EG at baseline, 24 (±4) and 48 (±4) weeks, by measuring the perfused boundary region (PBR, inversely proportional to EG thickness), in sublingual microvessels. In total, 66 consecutive PLWH (60 (90.9%) males) with a median age (interquartile range, IQR) of 37 (12) years, were enrolled. In total, 40(60.6%) received INSTI-based regimens. The mean (standard deviation) PBR decreased significantly from 2.17 (0.29) μm at baseline to 2.04 (0.26) μm (p = 0.019), and then to 1.93 (0.3) μm (p < 0.0001) at 24 (±4) and 48 (±4) weeks, respectively. PBR did not differ among treatment groups. PLWH on INSTIs had a significant PBR reduction at 48 (±4) weeks. Smokers and PLWH with low levels of viremia experienced the greatest PBR reduction. This study is the first to report the benefit of antiretroviral treatment on EG improvement in treatment-naïve PLWH and depicts a potential bedside biomarker and therapeutic target for CVD in PLWH.

The contemporary lifestyle of the last decade has undeniably caused a tremendous increase in oxidative-stress-inducing environmental sources. This phenomenon is not only connected with the rise of ROS levels in multiple tissues but is also associated with the induction of senescence in different cell types. Several signaling pathways that are associated with the reduction in ROS levels and the regulation of the cell cycle are being activated, so that the organism can battle deleterious effects. Within this context, autophagy plays a significant role. Through autophagy, cells can maintain their homeostasis, as if it were a self-degradation process, which removes the “wounded” molecules from the cells and uses their materials as a substrate for the creation of new useful cell particles. However, the role of autophagy in senescence has both a “dark” and a “bright” side. This review is an attempt to reveal the mechanistic aspects of this dual role. Nanomedicine can play a significant role, providing materials that are able to act by either preventing ROS generation or controllably inducing it, thus functioning as potential therapeutic agents regulating the activation or inhibition of autophagy.