Neuropathic pain, a debilitating nerve injury-induced condition, remains a significant clinical challenge. This study evaluates the effect of histone deacetylase 6 (HDAC6) inhibition in a spared nerve injury (SNI) mouse model. Systemic administration of the selective HDAC6 inhibitor ACY-1215 (20 mg/kg/day, 14 days), alleviated SNI-induced pain in mice of both sexes. ACY-1215 increased acetylated signal transducer and activator of transcription 3 (Ac-STAT3) and reduced phosphorylated STAT3 (p-STAT3) in the lumbar spinal cord of SNI mice. HDAC6 and p-STAT3 were expressed in spinal dorsal horn neurons, and SNI-enhanced HDAC6/STAT3 interaction was reversed by ACY-1215. Neuronal STAT3 overexpression induced pain hypersensitivity and elevated p-STAT3, tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), effects suppressed by ACY-1215. Cytokine profiling identified CC-chemokine ligand 7 (CCL7) as a key downstream effector of the HDAC6/STAT3 axis, with ACY-1215 attenuating SNI-induced CCL7 upregulation. HDAC6 knockdown in neurons reduced p-STAT3, while HDAC6 or STAT3 knockdown diminished CCL7 production. These findings demonstrate that ACY-1215 mitigates neuropathic pain by modulating STAT3 acetylation/phosphorylation and suppressing HDAC6/STAT3-driven CCL7 and cytokine release. This study underscores the role of the HDAC6/STAT3/CCL7 signaling axis in neuropathic pain and highlights the therapeutic potential of HDAC6 inhibitors for pain management.
Qian Feng,Laiwei Luo,Xindi Chen,Kaijie Zhang,Fang Fang,Zhaoxia Xue,Chao Li,Jiashun Cao,Jingyang Luo
The N-Acy-L-homoserine lactones (AHLs) mediated quorum sensing (QS) system exhibited important ecological significance in bacterial biofilm formation. However, the previous studies mainly focused on indigenous AHLs while the role of exogenous AHLs has remained unclear. This study evaluated the roles of exogenous AHLs on the biofilm formation of Pseudomonas aeruginosa . Both the C6-HSL and C8-HSL promoted the biofilm formation of P. aeruginosa with an enhancement of 2.47 and 1.88 times, respectively. Further analysis showed that exogenous AHLs contributed greatly to the adhesive ability instead of growth rate. Also, the bacterial motility and metabolic activities were significantly improved by AHLs. Moreover, the microbial functional genes ( i.e. lasI , lasR , rhlI and rhlR ) involved in regulating the biofilm formation were highly expressed in AHLs reactors. These findings expanded the knowledge of AHLs functions in mediating biofilm formation, and provided insightful guidance on the biofilm regulation in the wastewater treatment via biofilm technology.
Ji Wang,Jing Che,Xu-Song Wang,Lei Qin,Xu-Hui Huang
The levels of flavor compounds and hazardous compounds are important indicators for evaluating high-temperature roasted food. In this paper, the effect of tea pre-marination on non-volatile compounds, volatile compounds, and hazardous compounds in roasted chicken. The results showed that the total content of key umami non-volatile compounds in roasted chicken marinated with green tea, white tea, and black tea increased by 17.43 % to 100.11 %. The content of alkenes, alcohols, aldehydes, and ketones in high-temperature roasted chicken marinated with oolong tea and yellow tea was increased. Different teas had varying inhibitory effects on hazardous compounds in high-temperature roasted chicken, while green tea exhibited the highest inhibition efficacy. The inhibition rates of green tea for ACY, 5-HMF, HCAs, and PAHs were 72.12 %, 69.87 %, 92.49 %, and 14.92 %, respectively. Flavonoids in tea may play an important role in the flavor enhancement and hazardous compounds inhibition of high-temperature roasted chicken.
危险品化学品经营许可证（带存储）