In our experience, university students enrolling in health science and forensic science degrees show difficulty in retaining and integrating basic scientific knowledge learned in their first academic year. Furthermore, in the forensic sciences case, many students have oversimplified and unrealistic expectations as a result of the exposure to crime TV shows, internet blogs, and other social media platforms. Our pedagogical proposal is focused on second-year university students, aiming at promoting effective learning and the integration of scientific knowledge from previous courses, in this particular example, molecular and cell biology and biochemistry, with more advanced forensic courses, such as forensic anthropology and odontology. Teams composed of students and tutors from the teaching staff, with the help of dichotomous keys, are challenged to analyze a crime scene and choose the relevant evidence to further investigate, determine the scientific approach, execute the experimental work, interpret the results and, finally, resolve the case. To assess the pedagogical advantages and the receptivity of this project, a survey is to be carried out among students, and respective statistical analysis is also proposed. Finally, we hope this project outline may be adapted to other subjects, and, therefore, be used to address different pedagogical questions in forensic studies.

The search for alternative and effective therapies to fight cancer is one of the main goals of the pharmaceutical industry. Recently, ionic liquids (ILs) have emerged as potential therapeutic agents with antitumor properties. The goal of this study was to synthesize and evaluate the bioactivity of different ILs coupled with the active pharmaceutical ingredient (API) valproate (VPA) as an antitumor agent. The toxicity of the prepared ionic liquids was evaluated by the MTT cell metabolic assay in human neuroblastoma SH-SY5Y and human primary Gingival Fibroblast (GF) cell lines, in which they showed inhibitory effects during the study period. In addition, low cytotoxicity against GF cell lines was observed, suggesting that these compounds are not toxic to human cell lines. [C2OHDMiM][VPA] demonstrated an outstanding antitumor activity against SH-SY5Y and lower activity against the non-neoplastic GF line. The herein assessed compounds played an important role in the modulation of the signaling pathways involved in the cellular behavior. This work also highlights the potential of these ILs-API as possible antitumor agents.

Herein the quantitative synthesis of eight new mono- and dianionic Organic Salts and Ionic Liquids (OSILs) from alendronic acid (ALN) is reported by following two distinct sustainable and straightforward methodologies, according to the type of cation. The prepared ALN-OSILs were characterized by spectroscopic techniques and their solubility in water and biological fluids was determined. An evaluation of the toxicity towards human healthy cells and also human breast, lung and bone (osteosarcoma) cell lines was performed. Globally, it was observed that the monoanionic OSILs showed lower toxicity than the corresponding dianionic structures to all cell types. The highest cytotoxic effect was observed in OSILs containing a [C2OHMIM] cation, in particular [C2OHMIM][ALN]. The latter showed an improvement in IC50 values of ca. three orders of magnitude for the lung and bone cancer cell lines as well as fibroblasts in comparison with ALN. The development of OSILs with high cytotoxicity effect towards the tested cancer cell types, and containing an anti-resorbing molecule such as ALN may represent a promising strategy for the development of new pharmacological tools to be used in those pathological conditions.

AbstractNovel ionic liquids and organic salts based on mono‐ or dianionic zoledronate and protonated superbases, choline and n‐alkylmethylimidazolium cations, were prepared and characterized by spectroscopic and thermal analyses. Most of the prepared salts display amorphous structures and very high solubility in water and saline solutions, especially the dianionic salts. Among the zoledronate‐based ionic compounds, those containing choline [Ch] and methoxyethylmethylimidazolium [C3OMIM] cations appear to have significant cytotoxicity against human osteosarcoma cells (MG63) and low toxicity toward healthy skin fibroblast cells. Because osteosarcoma is a bone pathology characterized by an increase in bone turnover rate, the results presented herein may be a promising starting point for the development of new ionic pharmaceutical drugs against osteosarcoma.

Bisphosphonates (BPs) are stable analogues of the Inorganic Pyrophosphate (PPi), an endogenous regulator of bone mineralization, which can resist the hydrolysis in the gastrointestinal tract. Their conformation allows targeting the bone as a result of their three-dimensional structure, which makes them primary agents against osteoclast-mediated bone loss. They are used in many bone pathological conditions, like bone metastasis, because of its ability to modulate bone metabolism into a less favorable place to cancer cell growth, through the inhibition of osteoclastogenesis and bone resorption. This review is focused on the mechanisms of action through which BPs affect the cellular activity and survival, mainly on their antitumoral effects. In conclusion, BPs are considered the primary therapy for skeletal disorders due to its high affinity for bone, but now they are also considered as potential antitumor agents due to its ability to induce tumor cell apoptosis, inhibition of cell adhesion, invasion and proliferation, modulation of the immune system to target and eliminate cancer cells as well as affect the angiogenic mechanisms. Like any other drug, they also have some adverse effects, but the most common, the acute phase reaction, can be minimized with the intake of calcium and vitamin D.

AbstractAntiepileptic drugs (AED) have been associated to in vivo deleterious consequences in bone tissue. The present work aimed to characterize the cellular and molecular effects of five different AED on human osteoclastogenesis and osteblastogenesis. It was observed that the different drugs had the ability to differentially modulate both processes, in a way dependent on the identity and dose of the AED. Shortly, valproic acid stimulated either osteoclastogenesis and osteoblastogenesis, whereas carbamazepine, gabapentin, and lamotrigine revealed an opposite behavior; topiramate elicited a decrease of osteoclast development and an increase in osteoblast differentiation. This is the first report describing the direct effects of different AED on human primary bone cells, which is a very important issue, because these drugs are usually consumed in long‐term therapeutics, with acknowledged in vivo effects in bone tissue.

: The unique properties of ionic liquids make them quite appealing for diverse applications, from “green” solvents (1st generation ionic liquids) to finely tuned materials (2nd generation ionic liquids). A decade ago, a 3rd generation of ionic liquids emerged which is focused on their prospective clinical applications, either as drugs per se or as adjuvants in drug formulations. In recent years, research focused on the use of ionic liquids for topical drug delivery has been increasing and holds great promise towards clinical application against skin cancers. This article highlights the growing relevance of ionic liquids in medicinal chemistry and pharmaceutical technology, which is opening new windows of opportunity.