-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
- Cosmetic Ingredient
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
iNature ferroptosis is a non-apoptotic cell death process that requires accumulation of cellular iron and lipid peroxides
.
In progressive rheumatoid arthritis (RA), synovial fibroblasts proliferate abnormally in the presence of elevated reactive oxygen species (ROS) and lipid oxidation
.
On February 3, 2022, Zhu Ping, Chen Zhinan, Wu Jiao, and Jiang Xuejun of Memorial Sloan Kettering Cancer Center published an online publication in Nature Communications entitled "TNF antagonist sensitizes synovial fibroblasts to ferroptotic cell death in collagen-induced arthritis mouse models" from Air Force Military Medical University.
", which used a mouse model of collagen-induced arthritis (CIA) to show that imidazolone erasin (IKE), a ferroptosis inducer, reduced the number of fibroblasts in the synovium
.
Data from single-cell RNA-sequencing further identified two groups of fibroblasts that were significantly sensitive to IKE-induced ferroptosis, and that ferroptosis-resistant fibroblasts were associated with increased TNF-related transcriptomes
.
Mechanistically, TNF signaling promotes cystine uptake and glutathione (GSH) biosynthesis, thereby protecting fibroblasts from ferroptosis
.
Finally, in the CIA model, low-dose IKE combined with the TNF antagonist etanercept induced fibroblast ferroptosis and delayed arthritis progression
.
Taken together, our findings suggest that the combined use of TNF inhibitors and ferroptosis inducers may be a potential candidate for RA treatment
.
Rheumatoid arthritis (RA) is an autoimmune inflammatory disease during which hyperplastic rheumatoid synovium covers the surface of cartilage and invades cartilage and bone, resulting in progressive joint destruction
.
Inflammation and disease progression can be effectively controlled by biotherapeutics targeting cytokines, such as TNF and IL-6, which contribute to the combined destruction and inflammation of RA
.
However, current treatments do not completely prevent progressive joint erosion and cure the disease
.
In addition, these treatments have similar upper therapeutic response limits
.
Therefore, there is a need to develop new therapeutic approaches to overcome the persistent inflammation of rheumatoid arthritis
.
Ferroptosis is a type of programmed necrosis caused by the accumulation of lipid peroxides caused by abnormal metabolic and biochemical processes
.
Although the physiological function of ferroptosis remains unproven, it has been shown to be an important cause of various pathological conditions, including ischemic organ damage and neurodegeneration, and can be used as a potential monotherapy or combination therapy Cancer Treatment Strategies
.
Recent studies suggest that ferroptosis may be involved in innate immunity, thereby playing a role in regulating inflammatory damage, signal transduction, and cell growth
.
However, knowledge about the exact link between inflammatory processes and ferroptosis is incomplete
.
As one of the major cell types in proliferating tissues, activated synovial fibroblasts promote inflammation, angiogenesis, and matrix degradation by producing inflammatory cytokines, pro-angiogenic factors, and matrix-degrading enzymes
.
Due to the dominant role of synovial fibroblasts in the pathophysiology of rheumatoid arthritis, new therapeutic approaches targeting activated synovial fibroblasts are in the spotlight
.
Treatment with cytokines reduced the destructive potential of fibroblasts but did not inhibit permanent activation of fibroblasts
.
High reactive oxygen species are thought to be involved in joint inflammation and destruction, and synovial fibroblasts proliferate abnormally under oxidative stress (which can lead to inflammation and joint damage), suggesting that synovial fibroblasts are protected in a pro-inflammatory environment , protected from oxidative stress
.
Therefore, the intervention of this protective signal may be used as a new strategy against fibroblast activation
.
In this study, we investigated how synovial fibroblasts in the hyperplastic rheumatoid synovium and synovial fluid of RA patients survive under physiological stress
.
Tumor necrosis factor (TNF) is an important pro-inflammatory cytokine in the pathogenesis of rheumatoid arthritis (RA).
GCLM) and glutamate-cysteine ligase regulatory subunit (GCLC), which inhibit the occurrence of ferroptosis, thereby promoting cellular uptake of cystine and biosynthesis of glutathione (GSH)
.
In the CIA model, the combination of a TNF antagonist and a low-dose ferroptosis inducer induces ferroptosis in synovial fibroblasts and significantly slows the progression of arthritis
.
Single-cell RNA sequencing reveals interactions between macrophage and fibroblast subsets via TNF signaling The underlying therapeutic potential of dysregulated fibroblasts in a broad range of diseases
.
Reference message: https://
.
In progressive rheumatoid arthritis (RA), synovial fibroblasts proliferate abnormally in the presence of elevated reactive oxygen species (ROS) and lipid oxidation
.
On February 3, 2022, Zhu Ping, Chen Zhinan, Wu Jiao, and Jiang Xuejun of Memorial Sloan Kettering Cancer Center published an online publication in Nature Communications entitled "TNF antagonist sensitizes synovial fibroblasts to ferroptotic cell death in collagen-induced arthritis mouse models" from Air Force Military Medical University.
", which used a mouse model of collagen-induced arthritis (CIA) to show that imidazolone erasin (IKE), a ferroptosis inducer, reduced the number of fibroblasts in the synovium
.
Data from single-cell RNA-sequencing further identified two groups of fibroblasts that were significantly sensitive to IKE-induced ferroptosis, and that ferroptosis-resistant fibroblasts were associated with increased TNF-related transcriptomes
.
Mechanistically, TNF signaling promotes cystine uptake and glutathione (GSH) biosynthesis, thereby protecting fibroblasts from ferroptosis
.
Finally, in the CIA model, low-dose IKE combined with the TNF antagonist etanercept induced fibroblast ferroptosis and delayed arthritis progression
.
Taken together, our findings suggest that the combined use of TNF inhibitors and ferroptosis inducers may be a potential candidate for RA treatment
.
Rheumatoid arthritis (RA) is an autoimmune inflammatory disease during which hyperplastic rheumatoid synovium covers the surface of cartilage and invades cartilage and bone, resulting in progressive joint destruction
.
Inflammation and disease progression can be effectively controlled by biotherapeutics targeting cytokines, such as TNF and IL-6, which contribute to the combined destruction and inflammation of RA
.
However, current treatments do not completely prevent progressive joint erosion and cure the disease
.
In addition, these treatments have similar upper therapeutic response limits
.
Therefore, there is a need to develop new therapeutic approaches to overcome the persistent inflammation of rheumatoid arthritis
.
Ferroptosis is a type of programmed necrosis caused by the accumulation of lipid peroxides caused by abnormal metabolic and biochemical processes
.
Although the physiological function of ferroptosis remains unproven, it has been shown to be an important cause of various pathological conditions, including ischemic organ damage and neurodegeneration, and can be used as a potential monotherapy or combination therapy Cancer Treatment Strategies
.
Recent studies suggest that ferroptosis may be involved in innate immunity, thereby playing a role in regulating inflammatory damage, signal transduction, and cell growth
.
However, knowledge about the exact link between inflammatory processes and ferroptosis is incomplete
.
As one of the major cell types in proliferating tissues, activated synovial fibroblasts promote inflammation, angiogenesis, and matrix degradation by producing inflammatory cytokines, pro-angiogenic factors, and matrix-degrading enzymes
.
Due to the dominant role of synovial fibroblasts in the pathophysiology of rheumatoid arthritis, new therapeutic approaches targeting activated synovial fibroblasts are in the spotlight
.
Treatment with cytokines reduced the destructive potential of fibroblasts but did not inhibit permanent activation of fibroblasts
.
High reactive oxygen species are thought to be involved in joint inflammation and destruction, and synovial fibroblasts proliferate abnormally under oxidative stress (which can lead to inflammation and joint damage), suggesting that synovial fibroblasts are protected in a pro-inflammatory environment , protected from oxidative stress
.
Therefore, the intervention of this protective signal may be used as a new strategy against fibroblast activation
.
In this study, we investigated how synovial fibroblasts in the hyperplastic rheumatoid synovium and synovial fluid of RA patients survive under physiological stress
.
Tumor necrosis factor (TNF) is an important pro-inflammatory cytokine in the pathogenesis of rheumatoid arthritis (RA).
GCLM) and glutamate-cysteine ligase regulatory subunit (GCLC), which inhibit the occurrence of ferroptosis, thereby promoting cellular uptake of cystine and biosynthesis of glutathione (GSH)
.
In the CIA model, the combination of a TNF antagonist and a low-dose ferroptosis inducer induces ferroptosis in synovial fibroblasts and significantly slows the progression of arthritis
.
Single-cell RNA sequencing reveals interactions between macrophage and fibroblast subsets via TNF signaling The underlying therapeutic potential of dysregulated fibroblasts in a broad range of diseases
.
Reference message: https://
