sumatriptan succinate (Zelrix / NP101 / Zecuity)

[Research progress of gut microbial metabolite succinate in inflammatory diseases].

Chen Y X YX, Niu M M, Du Y Y

Inflammatory diseases are pathological conditions precipitated by inflammation, with the gut microbiota and its metabolites playing a pivotal role in the inflammatory process. Succinate, a key metabolite generated by gut microorganisms, is implicated not only in the energy metabolism of the tricarboxylic acid cycle but also in the modulation of inflammatory processes via the succinate receptor 1-mediated immune regulatory pathway. This review provides a unified elaboration on the metabolic pathways and biological characteristics of succinate, the detection techniques for succinate, and the potential applications of succinate in the diagnosis and treatment of inflammatory diseases, aiming to provide a scientific basis for the development of relevant diagnosis and treatment strategies.

Correction to "d-α-Tocopherol Polyethylene Glycol Succinate-Based Redox-Sensitive Paclitaxel Prodrug for Overcoming Multidrug Resistance in Cancer Cells".

Bao Yuling Y, Guo Yuanyuan Y, Zhuang Xiangting X, Li Dan D et al.

Integrated Multi-Omics Links Bisphenol AF (BPAF) Exposure to Hepatic Lipid Metabolism Disruption via Succinate Dehydrogenase Dysfunction and Mitochondrial Impairment.

Wang Ning N, Xu Jing J, Leng Jing J, Xu Jia-Le JL et al.

Background/Objective: Bisphenol AF (BPAF), a fluorinated analogue of bisphenol A, is an environmental contaminant associated with hepatotoxicity and metabolic disruption. However, the systematic molecular mechanisms linking early transcriptional events to metabolic dysfunction in the liver remain poorly defined. The aim of this study is to elucidate the association between BPAF exposure and hepatic lipid accumulation by integrating transcriptomics, cellular metabolomics, and targeted phenotypic assays. Methods: We performed RNA-sequencing on livers from mice exposed to BPAF (0.1-10 mg/kg/day, 28 days), and performed non-targeted metabolomics on AML12 murine hepatocytes co-cultured with RAW264.7 macrophages in a Transwell system (0-2500 nM BPAF, 48 h). Key metabolic pathways were identified through integrated bioinformatics and validated using enzymatic assays, qRT-PCR, Western blotting, and phenotypic staining (lipid droplets, ROS). Results: Multi-omics integration revealed significant disruption of PPAR signaling and the tricarboxylic acid (TCA) cycle. A striking dose-dependent accumulation of succinate was observed in exposed cells, concomitant with a significant inhibition of succinate dehydrogenase (SDH) activity (52% reduction at 2500 nM, p < 0.001). Transcriptomic data confirmed the downregulation of mitochondrial fatty acid β-oxidation genes. Phenotypic validation indicated that BPAF exposure is associated with oxidative stress, pro-inflammatory cytokine release (TNF-α, IL-6), and pronounced intracellular lipid droplet accumulation in hepatocytes. Conclusions: This study suggests that BPAF exposure is associated with SDH dysfunction, TCA cycle arrest, and lipid dysregulation. Whether BPAF directly inhibits SDH or acts through upstream mitochondrial targets warrants further structural and kinetic investigation.

Fiber type specific tibialis anterior muscle atrophy and oxidative capacity reduction is contemporaneous with death of larger lumbar motor neurons in old rats.

Rooker Kathryn D KD, Hernandez-Vizcarrondo Genesis A GA, Cheung Sang Won SW, Mahadev Bhat Sanjana S et al.

Age-associated muscle weakness and atrophy of limb muscles, termed sarcopenia, is a major factor in the morbidity of the elderly. It is becoming increasingly recognized that a substantial contribution to the sarcopenic phenotype arises from motor neuron (MN) death in old age and subsequent muscle denervation. In human and rodent models, mitochondrial dysfunction is a leading culprit in both muscle and MN deterioration with age. In other motor pools within the Fischer 344 (F344) aging rat model, we showed that sarcopenia is selective to type IIx/b muscle fibers. We also showed a loss of larger MNs and denervation of the IIx/b fibers, which together comprise more fatigable fast (type FF) motor units. This selective vulnerability of larger MNs and type IIx/b muscle fibers to sarcopenia is further reflected by reductions in oxidative capacity of IIx/b fibers, as assayed by determining the maximum velocity of the succinate dehydrogenase reaction (SDHmax). Here, we hypothesize similar changes will occur in F344 tibialis anterior (TA) muscle from young (6-months) and old (24-months) groups. We also predict lumbar MN death in young and old F344 rats. We found selective atrophy of type IIx/b fibers in the TA from old rats. In old age, SDHmax was reduced but only in IIx/b TA fibers. These muscle observations were concomitant with the death of larger lumbar MNs in old age. This study indicates the remarkable selectivity of type FF TA motor units to age-associated perturbations and sarcopenia.