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Objective: To study the protective effect of cannabidiol (CBD) on rats with pulmonary fibrosis and explore the possible mechanism of the use of CBD in the treatment of pulmonary fibrosis. Methods: Sixty SD rats were randomly divided into the normal control group, model group, prednisone group, CBD low, medium and high dose groups (12, 36, 108 mg/kg, ig),10 rats in each group. Except for the normal control group, the other 5 groups were all induced by tracheal injection of bleomycin to rat models of pulmonary fibrosis. After modeling, the rats were given intragastric administration once a day for 28 consecutive days and samples were taken. The degree of pulmonary edema was detected; the pathological changes of lung tissue were observed by HE and Masson staining; tumor necrosis factor a (TNF-a), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and lung tissue superoxide dismutase (SOD), malondialdehyde (MDA), hydroxyproline (HYP) contents were measured by ELISA, transforming growth factor-ß1 (TGF-ß1) and a-smooth muscle protein (a-SMA) concentration were detected by immunocytochemical method, real-time fluorescent quantitative PCR (qRT-PCR) method was used to detect the mRNA expression levels of TGF-ß1,a-SMA, Nrf2 and nuclear transcription factor-κB p65 (NF-κB p65). Results: The lung organ coefficient and W/D value were significantly decreased in the CBD administration group (P<0.05); medium and high doses of CBD could reduce the number of collagen fibers and fibroblasts; the pulmonary fibrosis in the low, medium, and high dose groups of CBD was significantly lower. The levels of TNF-a, IL-1ß, and IL-6 in rat serum, as well as MDA and HYP in lung tissue, were significantly lower compared to the model group. Additionally, the level of SOD was significantly increased (P<0.05); The expression of a-SMA was decreased compared with the model group (P<0.05); the contents of TGF-ß1, a-SMA and NF-κB p65 mRNA in lung tissue decreased, and the expression level of Nrf2 mRNA increased (P<0.05). Especially, the high-dose group had the most significant effect. Conclusion: CBD can significantly reduce the degree of pulmonary fibrosis in rats, and its potential mechanism may be related to inhibiting inflammatory response, enhancing antioxidant capacity and inhibiting the protein expression of TGF -ß1 and a-SMA. [ABSTRACT FROM AUTHOR]

Background: Endoscopic rubber band ligation (ERBL) is a nonsurgical technique for the treatment of symptomatic internal hemorrhoids but is limited by recurrence and post-procedural pain., Aim: To evaluate satisfaction, long-term recurrence, and post-procedural pain in managing internal hemorrhoids using a combination of polidocanol foam sclerotherapy and ERBL., Methods: This was a prospective, multicenter, randomized study. A total of 195 consecutive patients diagnosed with grade II-III internal hemorrhoids were enrolled from four tertiary hospitals and randomly divided into a cap-assisted endoscopic polidocanol foam sclerobanding (EFSB) or an ERBL group. All patients were followed-up for 12 months. Symptom-based severity and post-procedural pain were assessed using a hemorrhoid severity score (HSS) and a visual analog scale (VAS). Continuous variables were reported as medians and interquartile range., Results: One hundred and ninety-five patients were enrolled, with 98 in the EFSB group. HSS was lower in the EFSB group than in the ERBL group at 8 weeks [4.0 (3.0-5.0) vs 5.0 (4.0-6.0), P = 0.003] and 12-month [2.0 (1.0-3.0) vs 3.0 (2.0-3.0), P < 0.001] of follow-up. The prolapse recurrence rate was lower in the EFSB group at 12 months (11.2% vs 21.6%, P = 0.038). Multiple linear regression analysis demonstrated that EFSB treatment [B = -0.915, 95% confidence interval (CI): -1.301 to -0.530, P = 0.001] and rubber band number (B = 0.843, 95%CI: 0.595-1.092, P < 0.001) were negatively and independently associated with the VAS score 24 hours post-procedure. The median VAS was lower in the EFSB group than in the ERBL [2.0 (1.0-3.0) vs 3.0 (2.0-4.0), P < 0.001]., Conclusion: Cap-assisted EFSB provided long-term satisfaction and effective relief from the recurrence of prolapse and pain 24 hours post-procedure., Competing Interests: Conflict-of-interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Lactate, previously considered a metabolic byproduct, is pivotal in cancer progression and maintaining the immunosuppressive tumor microenvironment. Further investigations confirmed that lactate is a primary regulator, introducing recently described post-translational modifications of histone and non-histone proteins, termed lysine lactylation. Pancreatic adenocarcinomas are characterized by increased glycolysis and lactate accumulation. However, our understanding of lactylation-related genes in pancreatic adenocarcinomas remains limited., Aim: To construct a novel lactylation-related gene signature to predict the survival of patients with pancreatic cancer., Methods: RNA-seq and clinical data of pancreatic adenocarcinoma (PDAC) were obtained from the GTEx (Genotype-Tissue Expression) and TCGA (The Cancer Genome Atlas) databases via Xena Explorer, and GSE62452 datasets from GEO. Data on lactylation-related genes were obtained from publicly available sources. Differential expressed genes (DEGs) were acquired by using R package "DESeq2" in R. Univariate COX regression analysis, LASSO Cox and multivariate Cox regressions were produced to construct the lactylation-related prognostic model. Further analyses, including functional enrichment, ESTIMATE, and CIBERSORT, were performed to analyze immune status and treatment responses in patients with pancreatic cancer. PDAC and normal human cell lines were subjected to western blot analysis under lactic acid intervention; two PDAC cell lines with the most pronounced lactylation were selected. Subsequently, RT-PCR was employed to assess the expression of LRGs genes; SLC16A1, which showed the highest expression, was selected for further investigation. SLC16A1-mediated lactylation was analyzed by immunofluorescence, lactate production analysis, colony formation, transwell, and wound healing assays to investigate its role in promoting the proliferation and migration of PDAC cells. In vivo validation was performed using an established tumor model., Results: In this study, we successfully identified 10 differentially expressed lactylation-related genes (LRGs) with prognostic value. Subsequently, a lactylation-related signature was developed based on five OS-related lactylation-related genes ( SLC16A1, HLA-DRB1, KCNN4, KIF23, and HPDL ) using Lasso Cox hazard regression analysis. Subsequently, we evaluated the clinical significance of the lactylation-related genes in pancreatic adenocarcinoma. A comprehensive examination of infiltrating immune cells and tumor mutation burden was conducted across different subgroups. Furthermore, we demonstrated that SLC16A1 modulates lactylation in pancreatic cancer cells through lactate transport. Both in vivo and in vitro experiments showed that decreasing SLC16A1 Level and its lactylation significantly inhibited tumor progression, indicating the potential of targeting the SLC16A1/Lactylation-associated signaling pathway as a therapeutic strategy against pancreatic adenocarcinoma., Conclusion: We constructed a novel lactylation-related prognostic signature to predict OS, immune status, and treatment response of patients with pancreatic adenocarcinoma, providing new strategic directions and antitumor immunotherapies., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)