Aims: Chronic diabetes complications, including diabetic nephropathy (DN), frequently result in end-stage renal failure. This study investigated empagliflozin (SGLT2i) effects on collagen synthesis, oxidative stress, cell survival, and protein expression in an LLC-PK1 model of DN. Methods: Combinations of high glucose (HG) and increasing empagliflozin concentrations (100 nM and 500 nM), as well as combinations of HG, H₂O₂, and empagliflozin, were used for cell culture treatment. The cell viability, glutathione (tGSH), ECM expression, and TGF-β1 concentration were measured. In addition, the protein expression of Akt, pAkt, GSK3, pGSK3, pSTAT3, and SMAD7 was determined. Results: The addition of both concentrations of empagliflozin to cells previously exposed to glucose and oxidative stress generally improved cell viability and increased GSH levels (p < 0.001, p < 0.05). In HG30/H₂O₂/Empa500-treated cells, significant increase in pSTAT3, pGSK3β, GSK3β, SMAD7, and pAKT levels (p < 0.001, p < 0.001, p < 0.05) was observed except for AKT. Lower drug concentrations did not affect the protein expression levels. Furthermore, empagliflozin treatment (100 nM and 500 nM) of HG30/H₂O₂-injured cells led to a decrease in TGF-β1 levels (p < 0.001). In cells exposed to oxidative stress and hyperglycemia, collagen production remained unchanged. Conclusion: Renoprotective effects of empagliflozin, in this LLC-PK1 cell model of DN, are mediated via activation of the Akt/GSK-3 signalling pathway, thus reducing oxidative stress-induced damage, as well as enhanced SMAD7 expression leading to downregulation of TGF-β1, one of the key mediators of inflammation and fibrosis.

Liver fibrosis represents one of the greatest challenges in medicine. The fact that it develops with the progression of numerous diseases with high prevalence (NAFLD, viral hepatitis, etc.) makes liver fibrosis an even greater global health problem. Accordingly, it has received much attention from numerous researchers who have developed various in vitro and in vivo models to better understand the mechanisms underlying fibrosis development. All these efforts led to the discovery of numerous agents with antifibrotic properties, with hepatic stellate cells and the extracellular matrix at the center of these pharmacotherapeutic strategies. This review focuses on the current data on numerous in vivo and in vitro models of liver fibrosis and on various pharmacotherapeutic targets in the treatment of liver fibrosis.

In recent years, the prevalence of laryngopharyngeal reflux has risen, especially among pediatric patients. The diagnosis of laryngopharyngeal reflux relies on patient history and clinical assessment using the Reflux Finding Score and Reflux Symptom Index as crucial diagnostic tools. Some studies have proposed a link between pepsin and laryngopharyngeal reflux, potentially triggering palatine tonsil hypertrophy. Our study aimed to investigate the correlation between laryngeal and pharyngeal manifestations of laryngopharyngeal reflux through two questionnaires and the presence of pepsin in saliva and palatine tonsils in a pediatric population. Pepsin in saliva was detected using a Western blot method, while immunohistochemistry assessed its presence in palatine tonsils. Although no statistically significant differences in Reflux Finding Score and Reflux Symptom Index were found between the immunohistochemistry-positive (IHC-positive) and immunohistochemistry-negative (IHC-negative) groups, median reflux symptom index and Reflux Finding Score values consistently trended higher in the IHC-positive group. This suggests a potential connection between elevated index values and pepsin presence in tonsillar tissue. Further investigations are essential to fully comprehend the clinical implications of these findings.

Sucralose is widely used as a non-nutritive sweetener (NNS). However, in order to justify its use as a non-nutritive food additive, sucralose would have to be metabolically neutral. The aim of this study was to examine whether sucralose altered the insulin signaling pathway in an in vitro cell model of Parkinson’s disease (PD)—the dopaminergic differentiated cell line SH-SY5Y. Cells were exposed to sucralose alone and in combination with either insulin or levodopa. Activation of the insulin signaling pathway was assessed by quantifying protein kinase B (AKT) and glycogen synthase kinase 3 (GSK3), as well as the phosphorylated forms of insulin-like growth factor 1 receptor (IGF1-R). Metabolic effects were assayed using MALDI-TOF MS analysis. In the cell viability test, 2 mM sucralose had a negative effect, and levodopa in all combinations had a positive effect. Sucralose treatment alone suppressed GSK3 and IGF1-R phosphorylation in a dose-dependent manner. This treatment also altered the metabolism of fatty acids and amino acids, especially when combined with insulin and levodopa. Suppression of the insulin signaling pathway and sucralose-induced changes in the metabolic profile could underlie a diet-acquired insulin resistance, previously associated with neurodegeneration, or may be an altered response to insulin or levodopa medical therapy.