Hepatocellular carcinoma (HCC) is one of the leading causes of death from cancer in the world. Recently, the effectiveness of new antiviral therapies and the HBV vaccine have reduced HCC’s incidence, while non-alcoholic steato-hepatitis is an emerging risk factor. This review focuses on antiangiogenic molecules and immune checkpoint inhibitors approved for HCC treatment and possible future approaches. Sorafenib was the first drug approved for the treatment of advanced HCC (aHCC) and it has been shown to increase survival by a few months. Lenvatinib, a multikinase inhibitor, has shown non-inferiority in survival compared with sorafenib and an improvement in progression-free survival (PFS). The combination of atezolizumab (an anti-PDL1 antibody) and bevacizumab (an anti-VEGF antibody) was the first drug combination approved for HCC, demonstrating improved survival compared with sorafenib (19.2 vs. 13.4 months). As a second line of therapy, three regimens (regorafenib, cabozantinib, and ramucirumab) have been approved for the treatment of aHCC after progression on sorafenib according to guidelines. Furthermore, nivolumab, pembrolizumab, and nivolumab plus ipilimumab have been approved by the FDA (2017, 2018, and 2020, respectively). Finally, immune target therapy, cancer vaccines, and epigenetic drugs represent three new possible weapons for the treatment of HCC.

Oxidative stress plays an important role in brain aging and in neurodegenerative diseases. New therapeutic agents are necessary to cross the blood–brain barrier and target disease pathogenesis without causing disagreeable side effects. Resveratrol (RSV) may act as a neuroprotective compound, but little is known about its potential in improving the cognitive and metabolic aspects that are associated with neurodegenerative diseases. The objective of this study was to investigate the protective effects and the underlying mechanisms of RSV against hypoxia-induced oxidative stress in neuronal PC12 cells. For the induction of the hypoxia model, the cells were exposed to oxygen-deprived gas in a hypoxic chamber. Cell cycle and apoptosis were analyzed by a fluorescence activated cell sorting (FACS) analysis. The intracellular reactive oxygen species (ROS) level was analyzed by using dichlorodihydrofluorescein diacetate (DCFDA) and 5-(and-6)-chloromethyl-2’,7’-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA) tests. The expression of activated caspase-3, -9, Bcl-2, Bax, p53, and SOD was investigated by a Western blot analysis. We found that hypoxia reduced PC12 viability by inducing apoptosis, while RSV treatment attenuated the ROS-induced damage by reducing caspase-3, -9, and the Bax/Bcl-2 ratio. The RSV treated groups were found to improve cellular health, with a 7.41% increase in the S phase population in the 10 µM group, compared to the control. Hence, RSV has a protective effect in neuronal cells and may halt the cell cycle in the G1/S phase to repair the intracellular damage. Therefore, RSV could be a good candidate to act as an antioxidant and promising preventive therapeutic agent in neurodegenerative diseases for personalized medicine.

Osteoarthritis is a very disabling disease that can be treated with both non-pharmacological and pharmacological approaches. In the last years, pharmaceutical-grade chondroitin sulfate (CS) and glucosamine emerged as symptomatic slow-acting molecules, effective in pain reduction and improved function in patients affected by osteoarthritis. CS is a sulfated glycosaminoglycan that is currently produced mainly by extraction from animal tissues, and it is commercialized as a pharmaceutical-grade ingredient and/or food supplement. However, public concern on animal product derivatives has prompted the search for alternative non-extractive production routes. Thus, different approaches were established to obtain animal-free natural identical CS. On the other hand, the unsulfated chondroitin, which can be obtained via biotechnological processes, demonstrated promising anti-inflammatory properties in vitro, in chondrocytes isolated from osteoarthritic patients. Therefore, the aim of this study was to explore the potential of chondroitin, with respect to the better-known CS, in an in vivo mouse model of knee osteoarthritis. Results indicate that the treatment with biotechnological chondroitin (BC), similarly to CS, significantly reduced the severity of mechanical allodynia in an MIA-induced osteoarthritic mouse model. Decreased cartilage damage and a reduction of inflammation- and pain-related biochemical markers were also observed. Overall, our data support a beneficial activity of biotechnological unsulfated chondroitin in the osteoarthritis model tested, thus suggesting BC as a potential functional ingredient in pharmaceuticals and nutraceuticals with the advantage of avoiding animal tissue extraction.

Traumatic brain injuries (TBI) refer to multiple acquired dysfunctions arising from damage to the brain caused by an external force, including rapid acceleration/deceleration and concussion. Among them, mild TBI (mTBI) accounts for most cases (up to 90%) of injuries. It is responsible for a variety of symptoms, including anxiety, depression, and cognitive impairments that remain difficult to be treated. It has been reported that regular physical activity, as well as, improving life quality, display a neuroprotective function, suggesting a possible role in post-traumatic rehabilitation. In this study, we investigated the effects of treadmill exercise in a mice mTBI model by behavioural, electrophysiological and neurochemical analysis. Daily exercise decreased anxiety, aggressive behavior, and depression in mTBI mice. Accordingly, electrophysiological and neurochemical maladaptive rearrangement occurring in the hippocampus of mTBI mice were prevented by the exercise.