JOURNAL OF NEUROSCIENCE
·
2024
·
IF 4.4
Jing Chen,Yuan Gao,Shu-Ting Bao,Ying-Di Wang,Tao Jia,Cui Yin,Cheng Xiao,Chunyi Zhou
The comorbidity of chronic pain and depression poses tremendous challenges for the treatment of either one because they exacerbate each other with unknown mechanisms. As the posterior insular cortex (PIC) integrates multiple somatosensory and emotional information and is implicated in either chronic pain or depression, we hypothesize that the PIC and its projections may contribute to the pathophysiology of comorbid chronic pain and depression. We show that PIC neurons were readily activated by mechanical, thermal, aversive, and stressful and appetitive stimulation in naïve and neuropathic pain male mice subjected to spared nerve injury (SNI). Optogenetic activation of PIC neurons induced hyperalgesia and conditioned place aversion in naïve mice, whereas inhibition of these neurons led to analgesia, conditioned place preference (CPP), and antidepressant effect in both naïve and SNI mice. Combining neuronal tracing, optogenetics, and electrophysiological techniques, we found that the monosynaptic glutamatergic projections from the PIC to the basolateral amygdala (BLA) and the ventromedial nucleus in the thalamus (VM) mimicked PIC neurons in pain modulation in naïve mice; in SNI mice, both projections were enhanced accompanied by hyperactivity of PIC, BLA and VM neurons, and inhibition of these projections led to analgesia, CPP, and antidepressant-like effect. The present study suggests that potentiation of the PIC-BLA and PIC-VM projections may be important pathophysiological bases for hyperalgesia and depression-like behavior in neuropathic pain, and reversing the potentiation may be a promising therapeutic strategy for comorbid chronic pain and depression.Significance Statement Treatment of chronic pain is quite challenging because of the involvement of central sensitization and emotional disorders. It is keenly demanding to search for brain circuits commonly or separately contributing to hyperalgesia and emotional dysfunction in chronic pain. The PIC is involved in both pain and emotional processing. But, the relationship between the malfunction in the PIC and the comorbidity of chronic pain and depression has not been elucidated. Here, we demonstrate that in chronic pain, PIC neurons became hyperactive, and their projections to the BLA and the VM of the thalamus were augmented; these alterations may confer hyperalgesia and depression-like behaviors in chronic pain. Therefore, these pathways may be potential therapeutic targets for comorbid chronic pain and depression.
研究领域:
神经科学
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疼痛研究
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行为神经科学
·
神经回路
✓ 已验证
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2023
·
IF 8.8
Yongshuai Jing,Yameng Zhang,Meng Yan,Ruijuan Zhang,Beibei Hu,Shiguo Sun,Danshen Zhang,Yuguang Zheng,Lanfang Wu
Crataegus pinnatifida is a common food in China, Europe and North America. In order to confirm polysaccharide was the material basis for C. pinnatifida to exert immune regulation. A polysaccharide (CPP) with a molecular weight of 13.58 kDa was isolated from C. pinnatifida . The structure of CPP was determined to be a backbone composed of → 3,5)-α- l -Ara f -(1→, with two branches consisting of → 4)-α- d -Gal p -(1 → and → 5)-α- l -Ara f -(1→, with α- l -Ara f and α- d -Man p as the terminal unit. CPP (10 ∼ 500 μg/mL) could promote the secretion of nitric oxide, interleukin-2, interleukin-6 and tumor necrosis factor-α in vitro . CPP could significantly restore the body weight of immunosuppressive mice and improve the immune organ index and interleukin-2, interleukin-6, and tumor necrosis factor-α secretion. In addition, CPP increased the abundance of Bacteroidetes and Verrucomicrobia and decreased the abundance of Proteobacteria at the phylum level. So CPP can regulate the gut microbiota and play an important role in immune regulation.
研究领域:
药理学
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免疫学
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微生物学
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食品科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POLYMER DEGRADATION AND STABILITY
·
2024
·
IF 6.3
Fubin Luo,Shuguang Yang,Zhehang Shi,Yingbing Zou,Hongzhou Li
Epoxy-based vitrimers appear as a promising alternative to common epoxy materials. Nevertheless, the possibility of epoxy vitrimers in practical applications is limited by their high flammability. In this study, a novel bio-based casein phosphopeptide chelating zinc (CPP-Zn) is purposely developed, specifically designed to serve as a flame retardant and smoke suppressant for epoxy vitrimer, operating through a condensed phase mechanism. To further enhance the fire safety of epoxy resins, DOPO derivative (DDP) is synthesized through grafting with bio-based itaconate and subsequently used as a synergistic flame retardant in combination with CPP-Zn. DDP exhibits gas phase flame retardant mechanism through the release of free radical scavangers generated during combustion. As a result of the combination of condensed and gas phase effect, the composite achieves self-extinguishing within 1 second, attains a V-0 rating in UL-94 testing, and boasts an LOI of 32.3 %. Additional, it shows a remarkable 73.7 % reduction in heat release rate (HRR) and 27.2 % in total smoke production (TSP) compared with neat epoxy vitrimer. The experimental results also evidence that the characteristic features of vitrimers, self-healing and recyclability, have been retained in the prepared flame-retarded composites. The remolded 50D/EST-25Cz is still able to maintain 72.2 % of its tensile strength . This opens promising avenues for the development of highly fire-safe and eco-friendly epoxy resins.
研究领域:
材料科学
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化学工程
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消防安全工程
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环境科学
✓ 已验证
产品关联
DOI
高影响因子
Stem Cell Research & Therapy
·
2022
·Vol. 13
·期 1
·1-16
·
IF 8.079
Cui XiaoLing,Wang XiaoTan,Wen Jie,Li Xiao,Li Nan,Hao XuXiao,Zhao BaoXiang,Wu Xunwei,Miao JunYing
Background Human dermal fibroblasts (HDFs) have the potential to differentiate into vascular endothelial cells (VECs), but their differentiation rate is low and the mechanism involved is not clear. The small molecule pathway controls the phenotype of fibroblasts by activating cellular signaling pathways, which is a more convenient method in the differentiation strategy of HDFs into VECs. Methods In this study, HDFs were treated with the different doses of CPP ((E)-4-(4-(4-(7-(diethylamino)-2-oxo-2H-chromene-3-carbonyl) piperazin-1-yl) styryl)-1-methylpyridin-1-ium iodide), and the mRNA and protein levels of HDFs were detected by qPCR, Western blot, flow cytometry and immunofluorescent staining. The matrigel assays, acetylated-LDL uptake and angiogenesis assays of chick embryo chorioallantoic membrane (CAM) and hindlimb ischemia model of nude mice were performed to evaluate the functions of VECs derived from HDFs. Results Here, we report that the small chemical molecule, CPP, can effectively induce HDFs to differentiate into VECs. First, we observed the morphological changes of HDFS treated with CPP. Flow cytometry, Western blot and qRT-PCR analyses showed that CPP effectively decreased the level of the HDFs-marker Vimentin and increased levels of the VEC-markers CD31, CD133, TEK, ERG, vWF, KDR and CDH5. Detection of the percentage of CD31-positive cells by immunofluorescent staining confirmed that CPP can effectively induce HDFs to differentiate into VECs. The results of Matrigel assays, DiI-ac-LDL uptake, angiogenesis assays on CAM and hindlimb ischemia model of nude mice showed that CPP-induced HDFs have the functions of VECs in vitro and in vivo. Western blot and qRT-PCR analysis showed that CPP induces HDFs to differentiate into VECs by promoting the expression of pro-angiogenic factors (VEGF, FGF-2 and PDGF-BB). Conclusions Our data suggest that the small chemical molecule CPP efficiently induces the differentiation of HDFs into VECs. Simultaneously, this new inducer provides a potential to develop new approaches to restore vascular function for the treatment of ischemic vascular diseases.
研究领域:
细胞生物学
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分子生物学
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血管生物学
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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