Curcumin is a naturally occurring polyphenol extracted from turmeric, that exhibits several challenging properties such as anti-inflammatory, antioxidant, lipid-modulating, anti-thrombotic, immunomodulatory, neuroprotective, hepatoprotective and anti-tumor activities. Dry eye disease (DED) is recognized as a multifactorial disorder of the tears and ocular surface, associated with different symptoms, visual disturbance, and tear film instability, accompanied by inflammation of the ocular surface. Inflammation contributes to dry eye disese and in turn dry eyes can lead to worsening inflammation. Protective effects of curcumin have been proved in different eye diseases such as uveitis, idiopathic orbital inflammation, glaucomatous optic neuropathy and diabetes. Considering this background, the aim of the present study was to investigate the effects of curcumin loaded liposomes on human corneal epithelial culture cells subjected to oxidative stress, in order to detect cells' defensive response to the oxidative stress in presence of curcumin and to determine the optimal concentration of curcumin loaded liposomes for ophthalmic topical therapy in ocular surface disorders. Results obtained demonstrated that curcumin was able to protect cells from oxidative stress induced by hydrogen peroxide by reducing inflammation and activation of TNF-α (p < 0.01 vs H₂O₂ cells), NF-kB (p < 0.01 vs H₂O₂ cells) and NLRP3 (p < 0.01 vs H₂O₂ cells) pathways. Moreover, our results evidenced that curcumin reduced the levels of Bax (p < 0.01 vs H₂O₂ cells), a well known proapoptotic protein, and enhanced Bcl-2 protein (p < 0.01 vs H₂O₂ cells), thus exerting protection against apoptosis in corneal cells. All together, these results confirm the neutralizing effects of curcumin on the oxidative stress induced changes in corneal epithelial cells that might prevent cells damage and death with successive promoting of the inflammatory cascade.

Background: Mild cognitive impairment is increasingly recognized as a precursor to more severe neurodegenerative conditions, particularly in the context of aging. Recent studies have highlighted the intersection of hearing loss and cognitive decline, suggesting that auditory deficits may exacerbate cognitive impairments in older adults, proposing the use of hearing aids to mitigate cognitive decline, and indicating that early intervention in hearing loss could be crucial for preserving cognitive function. The underlying mechanisms of the relationship between hearing and cognitive impairment may involve neuroinflammatory processes and neurodegeneration. Recent studies have evidenced the role of tau proteins and neurofilaments as biomarkers in the onset and progression of neurodegenerative diseases. Methods: We selected 30 subjects with age-related hearing loss, and we evaluated their cognitive status through the administration of screening tests, which also measured neurofilament light chain and phospho-tau 181 serum levels as biomarkers of neurodegeneration. The subjects were re-evaluated six months after the hearing aid fitting. Results: Patients with hearing impairment presented slightly altered results on cognitive tests, typical of a mild cognitive impairment. At the same time, serum levels of neurofilament light chain and phospho-tau 181 were significantly increased compared to the matched control group. After the hearing aids fitting, auditory, cognitive, and serum values results improved. Conclusions: The results of the study highlight the cognitive involvement in patients with hearing impairment and identify neurofilament light chain and phospho-tau 181 as serum biomarkers of neurodegeneration useful in monitoring the pathology.

Medication-related osteonecrosis of the jaw (MRONJ) is a complex condition associated with the use of antiresorptive drugs, such as bisphosphonates and denosumab. The condition is characterized by the presence of exposed bone in the maxillofacial region that fails to heal. MRONJ remains highly intractable, as its pathogenic mechanisms are not yet fully understood. It is therefore essential to elucidate the molecular mechanisms underlying the disease. MiRNA expression analysis and proteomic studies were performed on a selected cohort of patients with MRONJ on jawbone tissue, using qRT-PCR and 2D electrophoresis followed by mass spectrometry. MiRNAs and proteomics data validation was carried out by Western blot analysis of differentially expressed proteins highlighted by a proteome study and predicted targets of differentially expressed miRNAs. Nineteen miRNAs were overexpressed and two downregulated in jawbone tissue from all MRONJ patients. Notably, five of these dysregulated miRNAs are involved in the regulation of angiogenesis and desmosome functions, suggesting a potential link to the molecular alterations observed at the protein level. Proteomic analysis revealed decreased concentrations of the pigment epithelium-derived factor, and of desmoglein-1, a desmosomal cadherin. Validation analysis confirmed the dysregulation of pathways involved in bone remodeling and necroptosis. The pathophysiology of MRONJ arises from a complex interplay of factors, including impaired bone remodeling, affected angiogenesis, and altered cell adhesion and differentiation mechanisms, ultimately leading to necroptosis. Through proteomic analysis and validation of miRNA expression, our study proposes specific molecular alteration in MRONJ-compromised bone tissue, involving desmosomal component imbalance and angiogenesis inhibition.