Due to its exceptional physical properties, such as high electronic conductivity, good thermal stability, excellent mechanical strength, and chemical versatility, graphene has sparked a lot of interest in the scientific community for various applications. It has therefore been employed as an antibacterial agent, in photothermal therapy (PTT) and biosensors, in gene delivery systems, and in tissue engineering for regenerative purposes. Since it was first discovered in 1947, different graphene derivatives have been synthetized from pristine graphene. The most adaptable derivate is graphene oxide (GO). Owing to different functional groups, the amphiphilic structure of GO can interact with cells and exogenous or endogenous growth/differentiation factors, allowing cell adhesion, growth, and differentiation. When GO is used as a coating for scaffolds and nanomaterials, it has been found to enhance bone, chondrogenic, cardiac, neuronal, and skin regeneration. This review focuses on the applications of graphene-based materials, in particular GO, as a coating for scaffolds in bone and chondrogenic tissue engineering and summarizes the most recent findings. Moreover, novel developments on the immunomodulatory properties of GO are reported.

Snail slime (SS) is a viscous secretion obtained from different snail species. SS composition is variable according to factors such as the extraction method. Even if several papers have been published regarding this topic, the molecular mechanisms at the base of SS biological effects remain unexplored. Thus, the aim of this study is to evaluate the capability of SS, extracted with the cruelty-free Muller method, to promote viability and angiogenesis processes and, in parallel, to counteract inflammation occurrence on skin cell populations. SS was administered to keratinocytes, macrophages and fibroblasts, then cell viability, through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, cytotoxicity by lactate dehydrogenase (LDH) assay, morphology by haematoxylin-eosin staining, gene and protein expression through real-time polymerase chain reaction (PCR) and Western blot, cell cycle phases by flow cytometry, and collagen secretion using an enzyme-linked immunosorbent assay (ELISA) test, were measured. Our results evidence SS capability to promote fibroblast viability and to trigger recovery mechanisms by activating the Erk protein. Moreover, an appreciable anti-inflammatory effect due to the significant reduction in cyclooxygenase-2 expression, and a positive modulation of new blood vessel formation demonstrated by increased Angiopoietin 1 gene expression and a higher matrix deposition (evidenced by the augmented amount of released collagen I) can be identified. This evidence led us to assume that the Muller method extracted-SS represents a valuable and promising natural product suitable for cosmetic and skin care formulations.

Natural products have attracted attention due to their safety and potential effectiveness as anti-inflammatory drugs. Particularly, xanthones owning a unique 9H-xanthen-9-one scaffold, are endowed with a large diversity of medical applications, including antioxidant and anti-inflammatory activities, because their core accommodates a vast variety of substituents at different positions. Among others, α- and γ-mangostin are the major known xanthones purified from Garcinia mangostana with demonstrated anti-inflammatory and antioxidant effects by in vitro and in vivo modulation of the Nrf2 (nuclear factor erythroid-derived 2-like 2) pathway. However, the main mechanism of action of xanthones and their derivatives is still only partially disclosed, and further investigations are needed to improve their potential clinical outcomes. In this light, a library of xanthone derivatives was synthesized and biologically evaluated in vitro on human macrophages under pro-inflammatory conditions. Furthermore, structure–activity relationship (SAR) studies were performed by means of matched molecular pairs (MMPs). The data obtained revealed that the most promising compounds in terms of biocompatibility and counteraction of cytotoxicity are the ones that enhance the Nrf2 translocation, confirming a tight relationship between the xanthone scaffold and the Nrf2 activation as a sign of intracellular cell response towards oxidative stress and inflammation.

Eg5 is a kinesin essential in bipolar spindle formation, overexpressed in tumours, thus representing a new target in cancer therapy. We aimed at evaluating the anti-cancer activity of Eg5 thiadiazoline inhibitors 2 and 41 on gastric adenocarcinoma cells (AGS), focusing on the modulation of angiogenic signalling. Docking studies confirmed a similar interaction with Eg5 to that of the parent compound K858. Thiadiazolines were also tested in combination with Hesperidin (HSD). Cell cycle analysis reveals a reduction of G1 and S phase percentages when 41 is administered as well as HSD in combination with K858. Western blot reveals Eg5 inhibitors capability to reduce PI3K, p-AKT/Akt and p-Erk/Erk expressions; p-Akt/Akt ratio is even more decreased in HSD+2 sample than the p-Erk/Erk ratio in HSD+41 or K858. VEGF expression is reduced when HSD+2 and HSD+41 are administered with respect to compounds alone, after 72 h. ANGPT2 gene expression increases in cells treated with 41 and HSD+2 compared to K858. The wound-healing assay highlights a reduction in the cut in HSD+2 sample compared to 2 and HSD. Thus, Eg5 inhibitors appear to modulate angiogenic signalling by controlling VEGF activity even better if combined with HSD. Overall, Eg5 inhibitors can represent a promising starting point to develop innovative anti-cancer strategies.

Novel twenty-three 3(2H)-pyridazinone derivatives were designed and synthesized based on the chemical requirements related to the anti-proliferative effects previously demonstrated within this scaffold. The introduction of a piperazinyl linker between the pyridazinone nucleus and the additional (un)substituted phenyl group led to some compounds endowed with a limited cytotoxicity against human gingival fibroblasts (HGFs) and good anti-proliferative effects against gastric adenocarcinoma cells (AGS) as evaluated by MTT and LDH assays, using doxorubicin as a positive control. Successive analyses revealed that the two most promising representative compounds (12 and 22) could exert their effects by inducing oxidative stress as demonstrated by the hydrogen peroxide release and the morphological changes (cell blebbing) revealed by light microscopy analysis after the haematoxylin-eosin staining. Moreover, to further assess the apoptotic process induced by compounds 12 and 22, Bax expression was measured by flow cytometry. These findings enlarged our knowledge of the structural requirements in this scaffold to display valuable biological effects against cancerous cell lines.

Sustained oxidative stress and inflammation have been reported as the major factors responsible for the failure of tendon healing during rotator cuff tears (RCTs) and rotator cuff disease (RCD). Although, their therapeutic management remains still challenging. Carbonic anhydrases (CAs) are involved in many pathological conditions, and the overexpression of both CA9 and 12 in inflamed joints has been recently reported. Consequently, a selective CA9/12 inhibition could be a feasible strategy for improving tendon recovery after injury. In addition, since carbon monoxide (CO) has been proven to have an important role in modulating inflammation, CO releasing molecules (CORMs) can be also potentially suitable compounds. The present study aims at evaluating five newly synthesized dual-mode acting CA inhibitors (CAIs)-CORMs compounds, belonging to two chemical scaffolds, on tendon-derived human primary cells under H₂O₂ stimulation in comparison with Meloxicam. Our results show that compounds 2 and 7 are the most promising of the series in counteracting oxidative stress-induced cytotoxicity and display a better profile in terms of enhanced viability, decreased LDH release, and augmented tenocyte proliferation compared to Meloxicam. Moreover, compound 7, as a potent superoxide scavenger, exerts its action inhibiting NF-ĸB translocation and downregulating iNOS, whereas compound 2 is more effective in increasing collagen I deposition. Taken together, our data highlight a potential role of CA in RCTs and RCD and the prospective effectiveness of compounds acting as CAI-CORM during inflammation.