Zhoueriksen5299
Traumatic brain injury (TBI) is a common nervous system injury. However, the detailed mechanisms about functional dysregulation and dignostic biomarkers post-TBI are still unclear. So we aimed to identify potential differentially expressed proteins and genes in TBI for clinical diagnosis and therapeutic purposes.
Rat TBI model was established by the weight-drop method. First, through TMT-proteomics, we screened for the change in the proteins expression profile acute phase post-TBI. The DAVID and Reactome databases were used to analyze and visualize the dysregulation proteins. Then, using publicly available microarray datasets GSE45997, differentially expressed genes (DGEs) were identified for the 24h post-TBI stage. Also, the proteomic data were compared with microarray data to analyze the similarity.
We found significant proteomics and transcriptomic changes in post-TBI samples. 989, 881, 832, 1057 proteins were quantitated at 1h, 6h, 24h, and 3 d post-injury correspondingly. Concerning proteomics findBI.
Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease worldwide. Exogenous H
S has been shown to effectively mitigate NAFLD, although little is known about the underlying targets and molecular mechanisms.
C57BL/6 mice were fed with normal fat diet (NFD) or high fat diet (HFD) for a total 16weeks, and HFD-fed mice were treated with saline or NaHS beginning in 12th week. The combination analysis of metabolomics and proteomics of liver tissues was firstly performed to discover the candidate targets and potential molecular pathways involved in H
S mitigating the NAFLD.
Compared with NaCl, H
S relieved NAFLD by reducing liver weight, body weight and lipid accumulation in liver, and improving liver pathology and serum biochemical parameters. There were 40 overlapping metabolites in the intersection analysis between comparative analysis of HFD+NaCl vs NFD and HFD+NaHS vs HFD+NaCl based on liver metabolomics. Moreover, a total of 58 proteins were obtained whose changes were reversed after treatment with H
S. A combined analysis of liver metabolomics and proteomics was then conducted, revealing 8 shared molecular pathways, as well as the enrichment of unsaturated fatty acids. In addition, Plin2 may also be a potential target of H
S via the regulation of lipid droplet degradation in alleviating NAFLD.
We performed the first study combining metabolomics and proteomics to explore the mechanisms behind the alleviation of NAFLD by H
S. Our results not only provide evidence that H
S alleviates NAFLD but also reveals its possible molecular mechanisms and targets.
We performed the first study combining metabolomics and proteomics to explore the mechanisms behind the alleviation of NAFLD by H2S. Our results not only provide evidence that H2S alleviates NAFLD but also reveals its possible molecular mechanisms and targets.
Cancer pain seriously affects the life quality of patients. Morphine is commonly used for cancer pain, but tolerance development limits its clinical administration. Central immune signaling is important in the development of cancer pain and morphine tolerance. Cannabinoid receptor 2 (CB2) inhibits cancer pain and morphine tolerance by regulating central immune signaling. In the present study, we investigated the mechanisms of central immune signaling involved in morphine tolerance inhibition by the CB2 agonist AM1241 in cancer pain treatment.
Rats were implanted with tumor cells and divided into 4 groups Vehicle (PBS), 0.07μg AM1241, 0.03μg AM1241, and AM630 (10μg)+AM1241 (0.07μg). All groups received morphine (20μg/day, i.t.) for 8days. AM630 (CB2 antagonist) was intrathecally injected 30min before AM1241, and AM1241 was intrathecally injected 30min before morphine. Birabresib molecular weight The spinal cord (SC) and dorsal root ganglion (DRG) were collected to determine the expression of Toll-like receptor 4 (TLR4), the p38 mitogen-activated protein kinase (MAPK), microglial markers, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α.
The expression of TLR4, p38 MAPK, microglial markers, IL-1β, and TNF-α was significantly higher in AM1241-pretreated groups than in the vehicle group (P<0.05). No difference in microglial markers, IL-1β, and TNF-α expression was detected in the AM630+AM1241 group compared with the vehicle group.
Our results suggest that in a cancer pain-morphine tolerance model, an i.t. non-analgesic dose of AM1241 induces microglial activation and IL-1β TNF-α upregulation in SC and DRG via the CB2 receptor pathway.
Our results suggest that in a cancer pain-morphine tolerance model, an i.t. non-analgesic dose of AM1241 induces microglial activation and IL-1β TNF-α upregulation in SC and DRG via the CB2 receptor pathway.Insufficient T cell infiltration in triple-negative breast cancer (TNBC) has limited its response rate to immune checkpoint blockade (ICB) therapies and motivated the development of immunostimulatory approaches to enhance the ICB therapy. CXCR4 is a chemokine receptor highly upregulated both on cell surface and cytoplasm in tumor tissues. Activating CXCR4 has been associated with increased immunosuppression in the tumor microenvironment. Here, we developed a CXCR4-targeted liposomal formulation (Liposomal-AMD3100) to enhance therapeutic efficacy of AMD3100, a CXCR4 antagonist. Particularly, AMD3100 is not only encapsulated into the liposome but coated on the surface of the formulation to serve as a targeting moiety and a dual blocker capable of inhibiting CXCR4 activation extracellularly and intracellularly. The Liposomal-AMD3100 remodeled both immune and stromal microenvironment more efficiently compared with free AMD3100, indicating better pharmacodynamic profile of AMD3100 achieved by liposomal formulation. The combination of anti-PD-L1 with Liposomal-AMD3100 formulation exhibited an increased antitumor effect and prolonged survival time compared with monotherapies in a murine TNBC model (4T1). This work proves that immune activation via liposomal delivery of CXCR4 inhibitors has a great potential to expand ICB therapies to originally ICB-insensitive cancer types.
