Background and objectives: Each individual studies is limited to multi-factors and potentially lead to a significant difference of results among them. The present study aim to explore the critical genes related to the development of Esophageal squamous cell carcinoma (ESCC) by integrated transcriptomics and to investigate the clinical significance by experimental validation. Methods: Datasets of protein-coding genes expression which involved in ESCC were downloaded from Gene Expression Omnibus (GEO) database. The “Robustrankaggreg” package in language was used for data integration, and the different expression genes (DEGs) were identified based the cut-off criteria as follows: adjust p-value < 0.05, |fold change (FC)| ≥ 1.5; The protein expression of seed gene in 184 cases of primary ESCC tissues and 50 tumor adjacent normal tissues (at least 5 cm away from the tumor, and defind as the controls) were detected by immunohistochemistry; The relationship between the expression level of seed genes and clinical parameter were analyze. Enumeration data were represented by frequency or percentage (%) and were tested by x² test. The P value of less than 0.05 was considered statistically significant. Results: A total of 244 DEGs were identified by comparing gene expression patterns between ESCC patients and the controls based on integrating dataset of GSE77861, GSE77861, GSE100942, GSE26886, GSE17351, GSE38129, GSE33426, GSE20347 and GSE23400; The Cyclin-dependent kinase inhibitor 3 (CDKN3) were identified the top 1 seed gene of top cluster by use of protein-protein Interaction network and plug-in Molecular Complex Detection; The level of CDKN3 mRNA was significantly increased in ESCC patients compared to controls; The positive expression rate of CDKN3 protein in ESCC tissue samples was 32 and 61.4% in control, respectively. The correlations between the expression level of CDKN3 and lymph node metastasis or clinical staging of ESCC patients are statistically significant. Conclusion: Integrated transcriptomics is an efficient approach to system biology. By this procedure, our study improved the understanding of the transcriptome status of ESCC.

Alcoholic liver disease (ALD) is a major health burden linked to oxidative stress, gut dysbiosis, and disrupted hepatic metabolism. While Lactiplantibacillus plantarum ( L. plantarum ) has shown potential in alleviating ALD, the specific mechanisms and bioactive components remain unclear. This study investigated the hepatoprotective effects of L. plantarum fermentation liquid (PFL) and its key metabolite, 3,4-hydroxyphenyl lactic acid (HPLA), against alcohol-induced liver injury. Using acute and chronic alcohol intoxication mouse models, we demonstrated that PFL significantly reduced mortality, attenuated hepatocyte damage, and restored alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities. UHPLC-QTOF-MS/MS analysis identified HPLA as the primary active component in PFL, exhibiting potent antioxidant properties. In vitro and in vivo experiments revealed that HPLA mitigated oxidative stress by enhancing superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, reducing malondialdehyde (MDA) levels, and suppressing lipid accumulation. Mechanistically, network pharmacology and molecular validation highlighted that HPLA alleviated hepatic injury by modulating the EGFR/PPAR-α signaling axis, thereby counteracting alcohol-induced oxidative stress and lipid metabolism disorders. These findings elucidate a novel “gut-liver” axis mechanism mediated by HPLA, offering a theoretical foundation for the clinical application of L. plantarum and its metabolites in ALD management. Importance: Numerous animal studies and clinical trials have demonstrated the effectiveness of probiotics in treating alcoholic liver disease. In this study, we primarily created a mouse model for both acute and chronic alcoholism and discovered that Lactiplantibacillus plantarum fermentation solution significantly decreased the inflammatory response and oxidative stress caused by alcohol. Its key metabolite, 3,4-hydroxyphenyl lactic acid (HPLA), exhibited strong antioxidant properties, helping to reduce oxidative stress by preventing lipid accumulation. This research offers insights into how probiotic interventions can mitigate alcoholic liver damage, enhancing our understanding of the protective effects of Lactiplantibacillus plantarum and emphasizing the potential of its metabolite, HPLA, as a targeted treatment for alcoholic liver disease.

To investigate the expression and role of nicotinic acetylcholine α7 subunit (nAChRα7) in the hippocampus of rats with Parkinson's disease (PD) and Parkinson's disease dementia (PDD). PD model was established with 6-hydroxydopa. Then, methyllycaconitine was further used to prepare a PDD model. The behavioral indexes and malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured. The mRNA level and protein level of nAChRα7 in hippocampus was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western-blot, respectively. The α7nAchR and NeuN protein was detected by immunofluorescence. Compared with the PD model group, the escape latency of the PDD model group was significantly prolonged while the times of crossing platforms was significantly reduced (p < 0.05). The SOD level in the PDD and PD group decreased as compared with the control group (p < 0.05), while the MDA content increased (p < 0.05). The mRNA level and protein expression of nAChRα7 in the PDD and PD model group was significantly lower than that in the control group (p < 0.05). There was a significant difference in the nAChRα7 protein level between the PDD and PD model group (p < 0.05). Together, the nAChRα7 receptor level was significantly decreased in the PDD model group, indicating that the decrease in the nAChRα7 receptor levels is a possible mechanism of the pathogenesis of PDD.