Biomaterials: West China Hospital reveals molecular mechanism of energy metabolism by Mo2C nanoenzymes in the treatment of fibromyalgia

Associate Researcher Gong Meng's team, Institute of Disease Systems Genetics/Frontier Science Center of Disease Molecular Network/Proteomics-Metabolomics Platform, West China Hospital, and Li Tao, Research Team of Anesthesiology Surgery Center/Mitochondrial and Metabolism Research Laboratory, published the article "Integrated metabolomics revealed the" in Biomaterials (IF:15.
304) in July 2022 fibromyalgia-alleviation effect of Mo2C nanozyme through regulated homeostasis of oxidative stress and energy metabolism", Mo2C nanoenzymes were found for the first time to have a therapeutic effect on reserpine-induced fibromyalgia, For the first time, the molecular mechanism
of energy metabolism in the treatment of fibromyalgia was revealed with the help of comprehensive metabolomics technology.
This study believes that Mo2C nanoenzymes have the potential as a therapeutic drug for fibromyalgia, which provides new ideas
for the clinical treatment of fibromyalgia.

Zhang Dingkun, assistant researcher of proteomics-metabolomics platform, and Jiang Ling, Ph.
D.
of mitochondria and metabolism research laboratory, are co-first authors, and Gong Meng, associate researcher of proteomics-metabolomics platform, and Li Tao, researcher of mitochondrial and metabolism research laboratory, are co-corresponding authors
.
The research work was guided
by Professor Xiaohong of Pain and Professor Bairong Shen of the Institute of Disease Systematic Genetics.

Fibromyalgia (FM) is the most common cause of chronic muscle and bone pain, and the probability of occurrence in the population is increasing year by year
.
FM is associated with factors such as fatigue, anxiety, depression, sleep disturbance and cognitive dysfunction, and the quality of life of FM patients is significantly reduced, and mental status is also greatly affected
.
Since 1990, when the American College of Rheumatology developed the first diagnostic criteria for FM, FM has been considered a widespread chronic pain
.
FM currently affects almost 5% of the world's population, and most have a range of symptoms
caused by FM.
The presence and interaction of endogenous and exogenous factors in FM make it a very complex disease
.
However, novel treatments for FM are lacking and detailed mechanisms based on the molecular level remain unclear
.

Mo2C nanoenzymes were found to exhibit therapeutic effects on reserpine-induced FM in mouse models; At the same time, the FM model sample was studied by comprehensive metabolomics based on gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry, which revealed the molecular mechanism
of energy metabolism during treatment.

It was found that Mo2C nanozymes could mimic superoxide dismutase (SOD), glutathione oxidase (GPx) and catalase (CAT) to remove excess reactive oxygen species clusters (ROS) from plasma, and effectively promote metabolism related to energy metabolism in FM models, including glycolysis, citric acid cycle, pentose phosphate pathway, fatty acid biosynthesis and metabolism, and lipid biosynthesis and metabolism, and this effect is also an important factor for Mo2C nanozymes to inhibit oxidative stress and mitochondrial dysfunction
。 After Mo2C nanoenzyme treatment, many physiological indicators of FM mouse model also reached a homeostatic state similar to normal mice at the behavioral, histology and morphological
levels.
Comprehensive metabolomics results also show that the metabolic changes caused by Mo2C are mainly manifested in the changes in the levels of amino acids, organic acids, fatty acids, phospholipids, lysophospholipids and glycerides, and the excellent biological activity of Mo2C plays a crucial role
in the treatment of FM.

The study further suggests that the process of Mo2C nanoenzyme treatment of FM can be divided into the following steps: (1) Mo2C catalyzes the removal of excess ROS from plasma during blood transfusion; (2) Mo2C promotes the recovery of the gastrocnemius muscle from ROS-induced injury and oxidative stress; (3) protect cell membranes to reduce levels of pro-inflammatory cytokines; (4) inhibit mitochondrial damage; (5) Restore metabolic homeostasis
in the body.

Histology and pathology of Mo2C nanoenzymes in the treatment of FM

Water-soluble metabolomics study of Mo2C nanoenzymes in the treatment of FM

Based on the above results, Mo2C nanozymes have the potential to be used as FM therapeutics, and their effective scavenging of ROS in vivo to maintain normal metabolic homeostasis in vivo may be one of
the key mechanisms.
Although Mo2C nanozymes are difficult to clear from animal blood vessels, based on the results of the study, Mo2C nanozymes can be used to remove ROS from blood products in vitro or to develop biodegradable nanoenzymes to reduce possible adverse effects
.

Molecular mechanism of Mo2C nanoenzymes in the treatment of FM

This study uses comprehensive metabolomics technology to reveal the molecular mechanism of energy metabolism in the treatment of FM by Mo2C nanoase, which is an important attempt to expand the application field of Mo2C nanozyme biomedicine, and the therapeutic mechanism of Mo2C nanozymes for FM also provides new ideas
for the clinical treatment of FM.

Original link: