Carbon Dots (CDs) are the latest members of carbon-based nanomaterials, which since their discovery have attracted notable attention due to their chemical and mechanical properties, brilliant fluorescence, high photostability, and good biocompatibility. Together with the ease and affordable preparation costs, these intrinsic features make CDs the most promising nanomaterials for multiple applications in the biological field, such as bioimaging, biotherapy, and gene/drug delivery. This review will illustrate the most recent applications of CDs in the biomedical field, focusing on their biocompatibility, fluorescence, low cytotoxicity, cellular uptake, and theranostic properties to highlight above all their usefulness as a promising tool for cancer diagnosis and therapy.

Background: Palmitoylethanolamide (PEA) is an endogenous fatty acid amide displaying anti-inflammatory and analgesic actions. Moreover, several data have suggested that PEA reduced inflammation and tissue injury associated with spinal cord trauma and showed a regulatory role for peroxisome proliferator-activated receptor (PPAR)-α signaling in the neuroprotective effect of PEA. However, several other mechanisms could explain the anti-inflammatory and anti-hyperalgesic effects of PEA, including the activation of PPAR-δ and PPAR-γ. The aim of the present study was to carefully investigate the exact contribution of PPAR-δ and PPAR-γ in addition to PPAR-α, in the protective effect of PEA on secondary inflammatory damage associated with an experimental model of spinal cord injury (SCI).Methods: SCI was induced in mice through a spinal cord compression by the application of vascular clips (force of 24 g) to the dura via a four-level T5 to T8 laminectomy, and PEA (10 mg/kg, intraperitoneally, 1 and 6 hours after SCI) was injected into wildtype mice and into mice lacking PPAR-α (PPAR-αKO). To deepen the ability of specific PPAR-δ and PPAR-γ antagonists to reverse the effect of PEA, mice were administered GSK0660 or GW9662, 30 minutes before PEA injection.Results: Genetic ablation of PPAR-α in mice exacerbated spinal cord damage, while PEA-induced neuroprotection seemed be abolished in PPARαKO mice. Twenty-four hours after spinal cord damage, immunohistological and biochemical studies were performed on spinal cord tissue. Our results indicate that PPAR-δ and PPAR-γ also mediated the protection induced by PEA. In particular, PEA was less effective in PPAR-αKO, GSK0660-treated or GW9662-pretreated mice, as evaluated by the degree of spinal cord inflammation and tissue injury, neutrophil infiltration, proinflammmatory cytokine, inducible nitric oxide synthase expression and motor function. PEA is also able to restore PPAR-δ and PPAR-γ expression in spinal cord tissue.Conclusion: This study indicates that PPAR-δ and PPAR-γ can also contribute to the anti-inflammatory activity of PEA in SCI.

Neurodegenerative diseases (NDs) represents debilitating conditions characterized by degeneration of neuronal cells in specific brain areas, causing disability and death in patients. In the pathophysiology of NDs, oxidative stress, apoptosis and neuroinflammation have a key role, as demonstrated by in vivo and in vitro models. Therefore, the use of molecules with antioxidant and anti-inflammatory activities represents a possible strategy for the treatment of NDs. Many studies demonstrated the beneficial effects of fumaric acid esters (FAEs) to counteract neuroinflammation and oxidative stress. Among these molecules, dimethyl fumarate (DMF) showed a valid therapeutic approach to slow down neurodegeneration and relieve symptoms in patients with NDs. DMF is a methyl ester of fumaric acid and acts as modulator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway as well as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) translocation. Therefore, this review aims to examine the potential beneficial effects of DMF to counteract oxidative stress and inflammation in patients with NDs.

The major end-products of dietary fiber fermentation by gut microbiota are the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate, which have been shown to modulate host metabolism via effects on metabolic pathways at different tissue sites. Several studies showed the inhibitory effects of sodium propionate (SP) on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. We carried out an in vitro model of inflammation on the J774-A1 cell line, by stimulation with lipopolysaccharide (LPS) and H₂O₂, followed by the pre-treatment with SP at 0.1, 1 mM and 10 mM. To evaluate the effect on acute inflammation and superoxide anion-induced pain, we performed a model of carrageenan (CAR)-induced rat paw inflammation and intraplantar injection of KO₂ where rats received SP orally (10, 30, and 100 mg/kg). SP decreased in concentration-dependent-manner the expression of cicloxigenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) following LPS stimulation. SP was able to enhance anti-oxidant enzyme production such as manganese superoxide dismutase (MnSOD) and heme oxygenase-1 (HO-1) following H₂O₂ stimulation. In in vivo models, SP (30 and 100 mg/kg) reduced paw inflammation and tissue damage after CAR and KO₂ injection. Our results demonstrated the anti-inflammatory and anti-oxidant properties of SP; therefore, we propose that SP may be an effective strategy for the treatment of inflammatory diseases.

Background: There is a growing realization that the gut–brain axis signaling is critical for maintaining the health and homeostasis of the Central Nervous System (CNS) and the intestinal environment. The role of Short-Chain Fatty Acids (SCFAs), such as Sodium Propionate (SP) and Sodium Butyrate (SB), has been reported to counteract inflammation activation in the central and Enteric Nervous System (ENS). Methods: In this study, we evaluated the role of the SCFAs in regulating the pathophysiology of migraine and correlated dysregulations in the gut environment in a mouse model of Nitroglycerine (NTG)-induced migraine. Results: We showed that, following behavioral tests evaluating pain and photophobia, the SP and SB treatments attenuated pain attacks provoked by NTG. Moreover, treatments with both SCFAs reduced histological damage in the trigeminal nerve nucleus and decreased the expression of proinflammatory mediators. Ileum evaluation following NTG injection reported that SCFA treatments importantly restored intestinal mucosa alterations, as well as the release of neurotransmitters in the ENS. Conclusions: Taken together, these results provide evidence that SCFAs exert powerful effects, preventing inflammation through the gut–brain axis, suggesting a new insight into the potential application of SCFAs as novel supportive therapies for migraine and correlated intestinal alterations.

Introduction: N-palmitoylethanolamine (PEA) is an endogenous fatty acid amide belonging to the family of theN-acylethanolamines (NAEs). Recently, several studies demonstrated that PEA is an important analgesic, antiinflammatory, and neuroprotective mediator. The aim of this study was to investigate the effect of co-ultramicronized PEA + luteolin formulation on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA).Methods: CIA was induced by an intradermally injection of 100 μl of the emulsion (containing 100 μg of bovine type II collagen (CII)) and complete Freund adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Mice subjected to CIA were administered PEA (10 mg/kg 10% ethanol, intraperitoneally (i.p.)) or co-ultramicronized PEA + luteolin (1 mg/kg, i.p.) every 24 hours, starting from day 25 to 35.Results: Mice developed erosive hind-paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hindpaws. The incidence of CIA was 100% by day 28 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period with a resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint. Treatment with PEA or PEA + luteolin ameliorated the clinical signs at days 26 to 35 and improved histologic status in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in PEA + luteolin-treated mice, as indicated by nitrotyrosine and malondialdehyde (MDA) levels. Plasma levels of the proinflammatory cytokines and chemokines were significantly reduced by PEA + luteolin treatment.Conclusions: We demonstrated that PEA co-ultramicronized with luteolin exerts an antiinflammatory effect during chronic inflammation and ameliorates CIA.