Lipidomic analyses have suggested that palmitic acid (PA) is linked to gastric cancer. However, its effects and action mechanisms remain unclear. Therefore, we evaluated the effects of PA on cell proliferation, invasion, and apoptosis in human gastric cancer, as well as the role of p-STAT3 in mediating its effects. The results of the MTT and colony formation assays revealed that PA blocked gastric cancer cell proliferation in a concentration-dependent manner. The EdU-DNA assay indicated that 50 μM of PA could block gastric cell proliferation by 30.6–80.0%. The Transwell assay also confirmed the concentration dependence of PA-induced inhibitory effect on cell invasion. The flow cytometry analysis indicated that PA treatment for 18 h could induce gastric cancer cell apoptosis. The immunohistochemical staining revealed that p-STAT3 levels were higher in the gastric cancer tissues than in the control tissues. We demonstrated that PA treatment for 12 h decreased the expressions of p-STAT3, p-JAK2, N-cadherin, and vimentin, and inhibited the nuclear expression of p-STAT3 in gastric cancer cells. Finally, PA treatment (50 mg/kg) decreased gastric cancer growth (54.3%) in the xenograft models. Collectively, these findings demonstrate that PA inhibits cell proliferation and invasion and induces human gastric cancer cell apoptosis.

Background/Objectives: Ceramide, a sphingolipid metabolite, has emerged as a key player in various physiological and pathological processes. Changes in ceramide levels are associated with the occurrence and development of various diseases, highlighting its potential as a biomarker of various clinical diseases. Methods: The biosynthesis and metabolism of ceramide are discussed, along with its functions in cell signaling, apoptosis, and inflammation. This study further examines the potential of ceramide as a biomarker for disease diagnosis and treatment. Results: This article highlights the involvement of ceramide in several diseases, including cardiovascular diseases, dermatosis, cancer, neurodegenerative disorders and metabolic syndromes. For each disease, the potential of ceramide as a biomarker for disease diagnosis and prognosis is explored, and the feasibility of therapeutic strategies targeting ceramide metabolism are reviewed. Additionally, the challenges and future directions in the field of ceramide research are addressed. Conclusions: This review article provides an overview of the recent advances in understanding the role of ceramide in clinical diseases and its potential as a diagnostic and therapeutic tool.

Background: Our previous study showed that antibiotic exposure was linked to depressive symptomatology in community-dwelling older adults in China. Our current study aims to explore the underlying mechanisms by assessing the intermediated effects of circulating short-chain organic acids (SCOAs) on this association. Methods: Depressive symptoms were screened by the 30-item Geriatric Depression Scale (GDS-30). Urinary concentrations of antibiotics and serum SCOAs were measured using a liquid chromatography–mass spectrometry method. Results: Increased exposure to sulfadiazine, azithromycin, tetracyclines, or veterinary antibiotics (VAs) was positively associated with GDS-30 scores. Tetracycline reduced levels of caproic acid, iso-butyric acid, and iso-caproic acid (iso-CA), with iso-CA concentration inversely correlating with GDS-30 scores, while β-hydroxybutyric acids showed a positive correlation. The mediating effect of serum iso-CA on the association between depression and ofloxacin, with a mediating effect of 25.3%, and the association between depression and tetracycline, with a mediating effect of 46.3%, were both statistically significant, indicating partial mediation. Conclusions: Antibiotics may affect the levels of SCOAs in older adults and could potentially contribute to depressive symptoms by influencing alterations in serum iso-CA levels.

Background: Severe obesity is associated with both circadian rhythm disturbances and cognitive deficits; however, the specific role of melatonin rhythmicity in neurocognitive dysfunction remains poorly understood. This study aimed to investigate the relationship between detailed salivary melatonin secretion profiles and cognitive performance across multiple domains in patients with severe obesity awaiting bariatric surgery. Methods: A total of 54 participants underwent salivary melatonin sampling at seven overnight time points. Cosinor analysis was used to extract circadian parameters, including mesor, amplitude, and acrophase. Neuropsychological assessments evaluated executive function, processing speed, memory, and general intelligence. The primary outcome was performance on the Stroop test, which captures core aspects of processing speed, executive function, and attention. Other neuropsychological measures, including IQ, MQ, and Trail Making Test performance, were considered secondary outcomes. Multivariable linear regression models, adjusted for demographic and metabolic covariates, were used to examine the associations between melatonin parameters and cognitive outcomes. Results: Participants exhibited substantial interindividual variation in melatonin profiles. A later melatonin acrophase was significantly associated with reduced processing speed, executive function, and attention, as reflected by longer completion times on the Stroop test ( β values ranged from 3.11 to 9.90, FDR-adjusted P < 0.05). The amplitude of melatonin secretion demonstrated a much weaker association with cognitive performance. Although nominal associations were observed between lower amplitude and slower Stroop Color Naming ( β = −1.22, 95% CI: −2.26 to −0.18, P = 0.023) and Incongruent ( β = −2.43, 95% CI: −4.74 to −0.11, P = 0.040) times, neither of these findings remained significant after FDR correction, indicating they may be due to chance. Conclusions: A later melatonin acrophase was associated with poorer cognitive performance in individuals with severe obesity undergoing evaluation for bariatric surgery. Larger longitudinal studies are needed to validate this association and determine whether changes in circadian timing are related to cognitive trajectories after bariatric surgery.