Downregulation of NF-κB by Shp-1 Alleviates Cerebral Venous Sinus Thrombosis-Induced Brain Edema Via Suppression of AQP4.

Aquaporin 4 (AQP4), a water channel protein, has been well studied in arterial stroke-induced brain edema. However, the role of AQP4 in cerebral venous sinus thrombosis (CVST) has not been reported. Here, we showed that AQP4 expression was increased in the brain of a rat CVST model, whereas inhibition of AQP4 decreased cerebral edema. Subsequent experiments showed that Shp-1 (Src homology 2-containing phosphatase-1) expression and NF-κB phosphorylation were upregulated after CVST. We found that Shp-1 inhibition resulted in enhancement of NF-κB activation and increased AQP4 expression accompanied by aggravated brain edema. We further showed that NF-κB inhibition led to decreased AQP4 expression and subsequent attenuation of brain edema but had no significant effect on Shp-1 expression. These results provide the first evidence suggesting that downregulation of NF-κB by Shp-1 alleviates CVST-induced brain edema through suppression of AQP4.

CCL14 exacerbates intraplaque vulnerability by promoting neovascularization in the human carotid plaque.

OBJECTIVE: To examine the role of CCL14 in the neovascularization process and vulnerability progression within carotid plaques by investigating the mechanism of CCL14 regulation of VEGF-A. METHODS: We first performed histological analysis and immunohistochemical staining of human carotid plaque tissue to detect the expression of CCL14, JAK2, STAT3 and VEGF-A. We next examined the protein expression of CCL14, VEGF-A, JAK2, STAT3, and phosphorylation of JAK2 and STAT3 in human carotid atherosclerotic plaques by Western blotting. Finally, we performed in vitro culture of human umbilical vein endothelial cells (HUVEC). In the tube formation assay of HUVEC, we added CCL14 siRNA or VEGF-A siRNA to the culture medium using lentiviral transfection to knock down CCL14 or VEGF-A and grouped them for control assays, and detected the changes in the expression of the above proteins using Western blotting. RESULTS: Histological and Western blotting analysis of human carotid plaque samples showed that the expression of CCL14 and VEGF-A was higher in the vulnerable plaques than in stable plaques. In the in vitro cultures of HUVEC, CCL14 was found to increase the number and length of intercellularly generated tubular structures. CCL14 increases VEGF-A expression via activating JAK2/STAT3 signaling. CONCLUSION: In the human carotid plaques, CCL14 promotes angiogenesis by upregulation of VEGF-A via JAK2/STAT3 pathway and thus drives the progression of carotid plaques vulnerability.

Genetic Analysis and Construction of a Fingerprint for Licensed Triadica sebifera Cultivars Using SSR Markers.

Triadica sebifera is an important landscaping tree species because of its colorful autumn leaves. In recent years, some cultivars have been bred and licensed, but it can be difficult to identify them from their morphological traits due to their similar phenotypes. To explore the genetic relationships and construct a fingerprint of the cultivars, the licensed T. sebifera cultivars were analyzed using SSR markers. A total of 179 alleles were identified among the 21 cultivars at 16 SSR loci, and these alleles exhibited a high level of genetic diversity (He = 0.86). The genetic variations mainly occurred among cultivars based on an analysis of molecular variance (AMOVA). According to phylogenetic analysis, principal coordinate analysis (PCoA), and Bayesian clustering analysis, the genetic relationships were independent of geographic distances, which may be mainly due to transplantations between regions. Some cultivars with different leaf colors showed obvious genetic differentiation and may be preliminary candidates for cross-breeding. Finally, the fingerprint for the licensed cultivars was constructed with two SSR markers. The results of this study can provide technical support for the application and legal protection of licensed Triadica sebifera cultivars.

Dimethyl Itaconate Reduces Cognitive Impairment and Neuroinflammation in APPswe/PS1ΔE9 Transgenic Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common type of dementia characterized by abnormal accumulation of amyloid-ß (Aß) plaques, neuroinflammation, and neuronal loss. Dimethyl itaconate (DI), a membrane-permeable derivative of itaconate, has been recently reported to limit inflammation. However, the effect of DI in the APPswe/PS1ΔE9 (APP/PS1) transgenic mouse model of AD remains unclear. We treated APP/PS1 mice with DI or saline. Our results showed that DI ameliorated the cognitive deficits of APP/PS1 mice. Further, DI significantly decreased brain Aß deposition and Aß levels, inhibited cell apoptosis, decreased hippocampal and cortical neuronal damage. We also found that DI promoted the expression of the Nrf2/HO-1 signaling pathway, while inhibited cognitive impairment, cell apoptosis, and the proinflammatory cytokine levels in the brains of APP/PS1 mice. Our results indicated that DI attenuated memory impairment and neuroinflammation via the Nrf2 signaling pathway in APP/PS1 mice, suggesting that DI might be recognized as a promising candidate for the treatment of AD.