Fatty acid amide hydrolase (FAAH) plays a key role in the control of cannabinoid signaling and it represents a promising therapeutic strategy for the treatment of a wide range of diseases, including neuropathic pain and chronic inflammation. Starting from kinetics experiments carried out in our previous work for the most potent inhibitor 2-amino-3-chloropyridine amide (TPA14), we have investigated its non-competitive mechanism of action using molecular dynamics, thermodynamic integration and QM-MM/GBSA calculations. The computational studies highlighted the impact of mutations on the receptor binding pockets and elucidated the molecular basis of the non-competitive inhibition mechanism of TPA14, which prevents the endocannabinoid anandamide (AEA) from reaching its pro-active conformation. Our study provides a rationale for the design of non-competitive potent FAAH inhibitors for the treatment of neuropathic pain and chronic inflammation.
Background: Casuarina equisetifolia, a crucial species of coastal windbreaks, is highly susceptible to infestation by Anoplophora chinensis. This stem-boring pest poses a significant threat to the health and sustainability of Casuarina equisetifolia forests. Understanding the molecular mechanisms underlying the host preference of A.
The conversion of methane and carbon dioxide to form C products is of great interest but presents a long-standing grand challenge due to the significant obstacle of activating the inert C-H and C═O bonds as well as forming the C-C bonds. Herein, the consecutive C-C coupling of CH and CO was realized by using heteronuclear metal cations CuTa, and the desorption of HC═C═O molecules was evidenced by state-of-the-art mass spectrometry. The CuTa reaction system is significantly different from the homonuclear metal systems of Cu and Ta.
Background: Esophageal cancer, particularly esophageal squamous cell carcinoma (ESCC), is a leading cause of cancer-related death and has a poor prognosis. Despite the advancements in multidisciplinary therapies, resistance to conventional treatments warrants the development of novel therapeutic strategies. Ferroptosis, a form of cell death dependent on intracellular iron, has emerged as a potential mechanism for targeting cancer cells resistant to apoptosis.
Shenxian-Shengmai (SXSM) is a Chinese patent medicine used in the treatment of sick sinus syndrome (SSS). However, its active chemical compounds and the underlying molecular mechanisms remain unclear. In this study, we researched the underlying mechanisms of SXSM in treating SSS.
The edible flower of Baroni, commonly known as "Huang Huacai" in China, has anti-depressant effects. However, targets and molecular mechanisms of Baroni edible flowers (HEF) in depression treatment are still unclear. The potential anti-depression targets in HEF were identified by the intersecting results from typical drug databases.
