ABSTRACT
BACKGROUND: The progression of gallbladder cancer (GBC) is accompanied by abnormal fatty acid ß-oxidation (FAO) metabolism. Different types of lipids perform various biological functions. This study aimed to determine the role of acyl carnitines in the molecular mechanisms of GBC progression. METHODS: Distribution of lipids in GBC was described by LC-MS-based lipidomics. Cellular localization, expression level and full-length of lncBCL2L11 were detected using fluorescence in situ hybridization (FISH) assays, subcellular fractionation assay and 5' and 3' rapid amplification of the cDNA ends (RACE), respectively. In vitro and in vivo experiments were used to verify the biological function of lncBCL2L11 in GBC cells. Methylated RNA Immunoprecipitation (MeRIP) was performed to detect the methylation levels of lncBCL2L11. RNA pull-down assay and RNA immunoprecipitation (RIP) assay were used to identify lncBCL2L11 interacting proteins. Co-Immunoprecipitation (Co-IP) and Western blot assay were performed to validate the regulatory mechanism of lncBCL2L11 and THO complex. RESULTS: Acylcarnitines were significantly up-regulated in GBC tissues. High serum triglycerides correlated to decreased survival in GBC patients and promoted tumor migration. LncBCL2L11 was identified in the joint analysis of highly metastatic cells and RNA sequencing data. LncBCl2L11 prevented the binding of THOC6 and THOC5 and causes the degradation of THOC5, thus promoting the accumulation of acylcarnitines in GBC cells, leading to the malignant progression of cancer cells. In addition, highly expressed acylcarnitines stabilized the expression of lncBCL2L11 through N6-methyladenosine methylation (m6A), forming a positive feedback regulation in tumor dissemination. CONCLUSIONS: LncBCL2L11 is involved in gallbladder cancer metastasis through FAO metabolism. High lipid intake is associated with poor prognosis of GBC. Therefore, targeting lncBCL2L11 and its pathway-related proteins or reducing lipid intake may be significant for the treatment of GBC patients.
Subject(s)
Carnitine/analogs & derivatives , Gallbladder Neoplasms , Humans , Gallbladder Neoplasms/genetics , In Situ Hybridization, Fluorescence , RNA , Lipids , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Nuclear Proteins/metabolism , RNA-Binding Proteins/geneticsABSTRACT
Electrochemical oxidation (EO) can effectively reduce the degree of humification and toxicity of landfill leachate by generating highly active oxidative species in situ. However, the selective and competitive oxidation of humic acid (HA) and ammonia (NH4+) and the role of different oxidative species during the EO process in complex aqueous conditions remain unclear. In this study, a nanostructured tin-antimony electrode (Ti/Sb-SnO2 NFs) was prepared and compared with three types of commercial electrodes (Ti/Ir-RuO2, Ti4O7, Ti/Sb-SnO2) in terms of electrochemical properties and electrocatalytic oxidation of HA and NH4+. The de-humification capacity, interactive effects of HA and NH4+ on each other's oxidation by different oxidative species, as well as the related oxidation byproducts were investigated. The differences in pollutant electrooxidation among the different electrodes were found to be insignificant. The presence of HA was found to be detrimental to NH4+ degradation while reducing the N2 conversion rate. Interestingly, NH4+ initially inhibited the degradation rates of HA while promoted the degradation and reduced the accumulation of organic chlorine during the later EO process. A proposed mechanism accounts for both competitive and promotional effects for simultaneous HA and NH4+ oxidation during the EO process.
ABSTRACT
Aberrant expression of G protein-coupled receptor class C group 5 member A (GPRC5A) has been reported in multiple cancers and is closely related to patient prognosis. However, the mechanistic role of GPRC5A in gallbladder cancer (GBC) remains unclear. Here, we determined tumor expression levels of GPRC5A and the molecular mechanisms by which GPRC5A regulates gallbladder cancer metastasis. We found that GPRC5A was significantly upregulated in GBC, correlating with poorer patient survival. Knocking down GPRC5A inhibited GBC cell metastasis both in vitro and in vivo. GRPRC5A knockdown resulted in downregulation of TNS4 expression through the JAK2-STAT3 axis. Clinically, GPRC5A expression positively correlated with TNS4. Finally, STAT3 bound to TNS4's promoter region, inducing its expression. Overall, GPRC5A showed high expression in GBC tissues, associated with poor patient prognosis. Our findings first demonstrate that the GPRC5A-JAK2-STAT3-TNS4 pathway promotes GBC cell metastasis, suggesting potential therapy targets.
Subject(s)
Gallbladder Neoplasms , Gene Expression Regulation, Neoplastic , Janus Kinase 2 , Receptors, G-Protein-Coupled , STAT3 Transcription Factor , Signal Transduction , Up-Regulation , Humans , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/genetics , Gallbladder Neoplasms/metabolism , Janus Kinase 2/metabolism , Janus Kinase 2/genetics , STAT3 Transcription Factor/metabolism , STAT3 Transcription Factor/genetics , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/genetics , Cell Line, Tumor , Animals , Male , Female , Mice , Prognosis , Neoplasm Metastasis , Mice, Nude , Cell Movement , Middle Aged , Mice, Inbred BALB CABSTRACT
Objective: To investigate the effectiveness of finger reconstruction using nail flap anastomosing the nerve branch of the first toe nail bed. Methods: Between January 2016 and December 2022, 18 patients (18 fingers) with thumb or finger nail bed defects were admitted. There were 12 males and 6 females, with an average age of 32 years (range, 19-42 years). Four cases were finger tip tissue damage caused by machine compression, and 4 cases were distal tissue necrosis after finger replantation. There were 9 cases of thumb injury, 3 cases of index finger injury, 5 cases of middle finger injury, and 1 case of ring finger injury. There were 11 cases of distal nail damage and 7 cases of distal nail root (including nail root) damage. The time from injury to admission was 1-5 hours, with an average of 2 hours. After debridement and anti-infection treatment for 5-7 days, the wounds in size of 1 cm×1 cm to 4 cm×3 cm were reconstructed by using nail flaps anastomosing the nerve branches of the first toe nail bed. The size of the nail flaps ranged from 1.5 cm×1.5 cm to 4.5 cm×3.5 cm. The donor sites were repaired with the flaps in 16 cases and skin graft in 2 cases. Results: All nail flaps, flaps, and skin grafts survived after operation and the wounds healed by first intention. All patients were followed up 6-12 months (mean, 10 months). The nails of 18 cases were all grown, in which 16 cases had smooth nails with satisfactory appearances, 1 case had uneven nails, and 1 case had obvious scar hyperplasia around the suture opening. At 6 months after operation, the two-point discrimination of the skin flap was 4-8 mm (mean, 6 mm). Meanwhile, the skin grafts and flaps at the donor sites regained protective sensation, good abrasion resistance, and had no negative effect upon walking and wearing shoes. Conclusion: The application of a nail flap that anastomoses the nerve branch of the first toe nail bed for finger reconstruction has minimal damage and can achieve good nail bed repair results.