Current Pharmaceutical Design - Current Issue

The metal oxide nanoparticles possess unique properties such as biological compatibility, superior reactivity, and capacity to develop reactive oxygen species, due to this they have drawn significant interest in cancer treatment. The various MONPs such as Cerium oxide, Copper oxide, Iron oxide, Titanium dioxide, and Zinc oxide have been investigated for several types of cancers including brain, breast, cervical, colon, leukemia, liver, lung, melanoma, ovarian, and prostate cancers. However, traditional physiochemical synthetic methods for MONPs commonly include toxic materials, a major concern that raises questions regarding their biocompatibility and safety.

This study aims to investigate the role of plant phytoconstituents in the development of MONPs via green synthesis and explore the therapeutic effectiveness of MONPs in treating several types of cancer. Primarily, it examines the potential of plant phytoconstituents (phenolic compounds, flavonoids, glycosides, alkaloids, etc.) in the development of MONPs as well as their improved ability to target numerous types of cancer.

A systemic search was conducted on recent literature, focusing on developing green MONPs by utilizing plants' phytoconstituents (plant extracts). The study of plant phytochemicals (present in different parts of a plant such as leaves, flowers, stems, peels, and roots) and their role in the synthesis of green metal oxide nanoparticles as well as their anticancer activity against several types of cancers was analyzed. Also focusing on their anticancer mechanism that involves ROS production, generates oxidative stress, and apoptosis leads to cancer inhibition.

Phytochemicals-mediated metal oxide nanoparticle synthesis revealed many advantages such as improved biological compatibility and enhanced sensitivity towards cancer cells. Phytochemicals present in plant extracts act as natural capping, reducing, and stabilizing agents, enhancing nanoparticle synthesis which leads to synergistic anticancer activity. Additionally, the natural antioxidant and anticancer activity of various phytochemicals enhances the therapeutic potential of metal oxide nanoparticles, producing them more effective against ROS-generated apoptosis and showing negligible toxicity towards normal cells.

The utilization of plant phytochemicals in metal oxide nanoparticle production presents a safe, eco-friendly, sustainable, and effective approach to developing effective and safer cancer nanomedicines. Green synthesis not only increases anticancer activity but also decreases the biocompatibility problems associated with the physiochemical synthetic approach. Further research needs to concentrate on improving this synergy to create a targeted phytochemical-based metal oxide nanoparticle for cancer therapeutics.

In recent years, sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as a valuable treatment for type 2 diabetes (T2D) and heart failure. Despite these medications seeming to be safe in older people, the literature about SGLT2i and frailty is still limited. This study aims to evaluate whether SGLT2i use is associated with increased survival in older adults and if frailty can affect the findings.

We enrolled over 65 patients admitted to the Geriatrics Wards at the University Hospital 'P. Giaccone' in Palermo, Italy, between December 2022 and May 2023. After 12 months of follow-up, various outcomes were assessed, including mortality, hospitalization, glycemic dysregulation, urinary tract infections, and falls. The association between SGLT2i use and mortality was analyzed and reported as hazard ratios (HRs) with their 95% confidence intervals (CIs).

A total of 80 patients were included in the study (mean age 79.5 ± 8.5 years; 50% were women). Patients using SGLT2i had a higher prevalence of T2D (p = 0.02) and cirrhosis (p = 0.001). After adjusting for potential confounders, SGLT2i use was significantly associated with a reduced mortality risk (HR = 0.53; 95% CI: 0.20-0.93; p = 0.02). When stratified by the presence of multidimensional frailty, SGLT2i use was significantly associated with a lower risk of mortality in frail patients (HR = 0.27; 95% CI: 0.06-0.88; p = 0.008), but not in robust ones.

In older frail patients, the use of SGLT2i is associated with reduced mortality after 12 months of follow-up. Further larger studies are needed to evaluate the role of these medications in older adults.

Chronic Kidney Disease (CKD) is recognized as a major global public health problem. Dialysis is the mainstay of treatment for patients with end-stage renal disease and can prolong survival in patients with CKD. As patient survival increases, the treatment of complications becomes more important. CKD-mineral and bone disorders (CKD-MBD) and renal anemia are common complications in patients with CKD. Cinacalcet is a calcimimetic for the treatment of secondary hyperparathyroidism (SHPT) in adult dialysis patients, which regulates the synthesis and secretion of parathyroid hormone by increasing the sensitivity of calcium-sensitive receptors. This retrospective study evaluated the efficacy of cinacalcet in dialysis patients.

Forty-six patients on dialysis with elevated parathyroid hormone were included. The selected patients have regular follow-up visits in our outpatient clinic and regular use of cinacalcet for no less than 6 months.

During the 6-month efficacy evaluation phase, cinacalcet not only reduced the levels of the intact parathyroid hormone (iPTH, P ≤ 0.05), serum calcium (P ≤ 0.01), and Ca×P (P ≤ 0.05) but also reduced weekly erythropoietin (EPO) dosage (P ≤ 0.01) and erythropoietin resistance index (ERI, P ≤ 0.05).

While controlling SHPT in patients with CKD, cinacalcet reduced EPO resistance and improved renal anemia. In conclusion, cinacalcet not only decreased the levels of the iPTH, serum calcium, and Ca×P but also reduced weekly EPO dosage and ERI levels. Controlling SHPT in patients with CKD, cinacalcet also reduced ERI and improved renal anemia.

The COVID-19 pandemic has necessitated rapid advancements in therapeutic discovery. This study presents an integrated approach combining machine learning (ML) and network pharmacology to identify potential non-covalent inhibitors against pivotal proteins in COVID-19 pathogenesis, specifically B-cell lymphoma 2 (BCL2) and Epidermal Growth Factor Receptor (EGFR).

Employing a dataset of 13,107 compounds, ML algorithms such as k-Nearest Neighbors (kNN), Support Vector Machine (SVM), Random Forest (RF), and Naïve Bayes (NB) were utilized for screening and predicting active inhibitors based on molecular features. Molecular docking and molecular dynamics simulations, conducted over a 100 nanosecond period, enhanced the ML-based screening by providing insights into the binding affinities and interaction dynamics with BCL2 and EGFR. Network pharmacology analysis identified these proteins as hub targets within the COVID-19 protein-protein interaction network, highlighting their roles in apoptosis regulation and cellular signaling.

The identified inhibitors exhibited strong binding affinities, suggesting potential efficacy in disrupting viral life cycles and impeding disease progression. Comparative analysis with existing literature affirmed the relevance of BCL2 and EGFR in COVID-19 therapy and underscored the novelty of integrating network pharmacology with ML. This multidisciplinary approach establishes a framework for emerging pathogen treatments and advocates for subsequent in vitro and in vivo validation, emphasizing a multi-targeted drug design strategy against viral adaptability.

This study's findings are crucial for the ongoing development of therapeutic agents against COVID-19, leveraging computational and network-based strategies.