Involvement of Substance P (SP) and Its Related NK1 Receptor in Primary Sjögren's Syndrome (pSS) Pathogenesis.

Primary Sjögren's Syndrome (pSS) is a systemic autoimmune disease that primarily attacks the lacrimal and salivary glands, resulting in impaired secretory function characterized by xerostomia and xerophthalmia. Patients with pSS have been shown to have impaired salivary gland innervation and altered circulating levels of neuropeptides thought to be a cause of decreased salivation, including substance P (SP). Using Western blot analysis and immunofluorescence studies, we examined the expression levels of SP and its preferred G protein-coupled TK Receptor 1 (NK1R) and apoptosis markers in biopsies of the minor salivary gland (MSG) from pSS patients compared with patients with idiopathic sicca syndrome. We confirmed a quantitative decrease in the amount of SP in the MSG of pSS patients and demonstrated a significant increase in NK1R levels compared with sicca subjects, indicating the involvement of SP fibers and NK1R in the impaired salivary secretion observed in pSS patients. Moreover, the increase in apoptosis (PARP-1 cleavage) in pSS patients was shown to be related to JNK phosphorylation. Since there is no satisfactory therapy for the treatment of secretory hypofunction in pSS patients, the SP pathway may be a new potential diagnostic tool or therapeutic target.

Post-COVID-19 Anosmia and Therapies: Stay Tuned for New Drugs to Sniff Out.

Background: Anosmia is defined as the complete absence of olfactory function, which can be caused by a variety of causes, with upper respiratory tract infections being among the most frequent causes. Anosmia due to SARS-CoV-2 infection has attracted attention given its main role in symptomatology and the social impact of the pandemic. Methods: We conducted systematic research in a clinicaltrials.gov database to evaluate all active clinical trials worldwide regarding drug therapies in adult patients for anosmia following SARS-CoV-2 infection with the intention of identifying the nearby prospects to treat Anosmia. We use the following search terms: "Anosmia" AND "COVID-19" OR "SARS-CoV-2" OR "2019 novel coronavirus". Results: We found 18 active clinical trials that met our criteria: one phase 1, one phase 1-2, five phases 2, two phases 2-3, three phases 3, and six phases 4 studies were identified. The drug therapies that appear more effective and promising are PEA-LUT and Cerebrolysin. The other interesting drugs are 13-cis-retinoic acid plus aerosolized Vitamin D, dexamethasone, and corticosteroid nasal irrigation. Conclusions: COVID-19 has allowed us to highlight how much anosmia is an important and debilitating symptom for patients and, above all, to direct research to find a therapy aimed at curing the symptom, whether it derives from SARS-CoV-2 infection or other infections of the upper airways. Some of these therapies are very promising and are almost at the end of experimentation. They also provide hope in this field, which not addressed until recently.

Neurons, Nose, and Neurodegenerative Diseases: Olfactory Function and Cognitive Impairment.

Olfactory capacity declines with aging, but increasing evidence shows that smell dysfunction is one of the early signs of prodromal neurodegenerative diseases such as Alzheimer's and Parkinson's disease. The study of olfactory ability and its role in neurodegenerative diseases arouses much interest in the scientific community. In neurology, olfactory impairment is a potential early marker for the onset of neurodegenerative diseases, but the underlying mechanism is poorly understood. The loss of smell is considered a clinical sign of early-stage disease and a marker of the disease's progression and cognitive impairment. Highlighting the importance of biological bases of smell and molecular pathways could be fundamental to improve neuroprotective and therapeutic strategies. We focused on the review articles and meta-analyses on olfactory and cognitive impairment. We depicted the neurobiology of olfaction and the most common olfactory tests in neurodegenerative diseases. In addition, we underlined the close relationship between the olfactory and cognitive deficit due to nasal neuroepithelium, which is a direct extension of the CNS in communication with the external environment. Neurons, Nose, and Neurodegenerative diseases highlights the role of olfactory dysfunction as a clinical marker for early stages of neurodegenerative diseases when it is associated with molecular, clinical, and neuropathological correlations.

Salivary Biomarkers in Oral Squamous Cell Carcinoma: A Proteomic Overview.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most frequent cancers worldwide. Endoscopic methods may be useful in the evaluation of oral injuries even though the diagnostic gold standard is a biopsy. Targeted screenings could be considered the best way to prevent the occurrence of oral cancer. Aimed to elucidate the potential identification of specific biomarkers of OSCC, the use of saliva is convenient and noninvasive. Many studies reported more than a hundred putative saliva biomarkers for OSCC, and proteogenomic approaches were fundamental to disclosing this issue. METHODS: Relevant literature published in the last few years was systematically searched on PubMed and we focused on articles about the use and study of salivary biomarkers in the diagnostics of head and neck cancer (n = 110). Thereafter, we performed a selection focusing on diagnosis with salivary proteomics in OSCC (n = 8). RESULTS: Saliva proteomics can be a source of biomarkers for OSCC. We reviewed literature of biomarker proteins in saliva that could also be evaluated as probable targets for non-invasive screening of oral neoplasm such as cytokines, matrix metalloproteinases, and acute-phase response proteins. CONCLUSIONS: The measurement of salivary biomarkers is a highly hopeful technique for the diagnosis of OSCC. Proteogenomic approaches could permit an accurate and early diagnosis of OSCC. This review seeks to generate an up-to-date view on translational OSCC issues by raising awareness of researchers, physicians, and surgeons. Renewed clinical studies, which will validate the sensitivity and specificity of salivary biomarkers, are necessary to translate these results into possible strategies for early diagnosis of OSCC, thus improving patient outcomes.