Efficacy of an oral suspension containing xyloglucan and pea proteins on a murine model of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is the most common foregut disease, affecting about 20% of the adult population. Esophageal epithelial barrier plays a fundamental role in the pathophysiology of GERD; however, pharmacological therapies mainly aim to reduce the acidity of the gastroesophageal environment rather than to protect esophageal tissue integrity. This study aims to evaluate the efficacy of an oral solution containing xyloglucan and pea proteins (XP) in reestablishing gastroesophageal tissue integrity and biochemical markers. To induce GERD, C57BL/6 mice were alternatively overfed and fasted for 56 days and then treated with XP, sodium alginate, omeprazole, or omeprazole+XP twice daily for 7 days. Gastric pain and inflammatory markers were evaluated after 3 and 7 days of treatment. After sacrifice, the esophagi and stomachs were surgically removed for macroscopic and histological examination. Gastric pain was significantly reduced at days 3 and 7 by XP, omeprazole, and omeprazole+XP, while alginates were ineffective at day 3. XP was able to diminish gastric macroscopic damage and demonstrated the same efficacy as omeprazole in reducing esophageal damage. XP significantly reduced histological damage, with an efficacy comparable to that of omeprazole, but superior to alginates. Inflammatory markers were significantly reduced by XP, with superior efficacy compared with alginates at day 7. Interestingly, XP was also able to significantly increase gastric pH. This study demonstrated that XP restored gastric homeostasis, improved esophageal integrity, and decreased inflammation and pain with a similar efficacy to omeprazole and greater than alginates.

Therapeutic Potential of BAY-117082, a Selective NLRP3 Inflammasome Inhibitor, on Metastatic Evolution in Human Oral Squamous Cell Carcinoma (OSCC).

Oral squamous cell carcinoma (OSCC) is a commonly occurring head and neck cancer and it is characterized by a high metastasis grade. The aim of this study was to evaluate for the first time the effect of BAY-117082, a selective NLRP3 inflammasome inhibitor, in an in vivo orthotopic model of OSCC and its role in the invasiveness and metastasis processes in neighbor organs such as lymph node, lung, and spleen tissues. Our results demonstrated that BAY-117082 treatment, at doses of 2.5 mg/kg and 5 mg/kg, was able to significantly reduce the presence of microscopic tumor islands and nuclear pleomorphism in tongue tissues and modulate the NLRP3 inflammasome pathway activation in tongue tissues, as well as in metastatic organs such as lung and spleen. Additionally, BAY-117082 treatment modulated the epithelial-mesenchymal transition (EMT) process in tongue tissue as well as in metastatic organs such as lymph node, lung, and spleen, also reducing the expression of matrix metalloproteinases (MMPs), particularly MMP2 and MMP9, markers of cell invasion and migration. In conclusion, the obtained data demonstrated that BAY-117082 at doses of 2.5 mg/kg and 5 mg/kg were able to reduce the tongue tumor area as well as the degree of metastasis in lymph node, lung, and spleen tissues through the NLRP3 inflammasome pathway inhibition.