Development of liver fibrosis is closely associated with angiogenesis and abnormal vascular remodeling. Recent studies have highlighted the importance of angiogenesis and vascular remodeling in fibrogenesis, the results that inhibition of angiogenesis is effective in suppression of liver fibrosis demonstrate that therapies with several molecular targets against angiogenesis, inflammation and fibrosis might be beneficial for the treatment of cirrhosis. However, there is some evidence that inhibition of angiogenesis can even worsen fibrosis. This article outlines recent advances regarding the interplay between inflammation, angiogenesis and fibrogenesis in terms of cellular and molecular mechanisms, and suggests a requirement of greater understanding to intervene in these key processes, such as liver sinusoidal endothelial cell fenestration and impact distinct chemokine actions driving monocyte migration and differentiation, for therapeutic benefit in the future.

Connexin43 has been shown to play a pivotal role in wound healing process. Wound repair is enhanced by acute downregulation of connexin43, by increasing proliferation and migration of keratinocyte and fibroblast. Angiogenesis is also a central feature of wound repair, but little is known about the effects of connexin43 modulation on functions of endothelial cells. We used connexin43 specific small interference RNA (siRNA) to reduce the expression of connexin43 in human umbilical vein endothelial cell (HUVEC), and investigated the effects of connexin43 downregulation on intercellular communication, viability, proliferation, migration and angiogenic activity of HUVEC. Treatment of siRNA markedly reduced the expression of connexin43 by -80% in HUVEC (P < 0.05), and decreased the intercellular communication by -65% (P < 0.05). The viability, proliferation, migration and angiogenic activity of HUVEC decreased significantly (P < 0.05), compared with that of the normal cells. The results suggest that temporally downregulation of connexin43 expression at early stage of wound to inhibit the abnormal angiogenesis characterized with leaky and inflamed blood vessels, maybe a prerequisite for coordinated normal healing process.

Objective:To explore CT imaging features related to disease-free survival (DFS) for gastric cancer (GC) patients with no clinical lymph node metastasis (cN0).Methods:From January 2005 to December 2018, 298 patients with GC were collected retrospectively in Peking University People′s Hospital. All the patients performed CT scanning before operation, and cT1-4N0M0 was defined by CT images. The clinical tumor stage (cT), extramural vessel invasion (EMVI), tumor morphological type, location and size were defined and recorded based on preoperative contrast-enhanced CT images. According to the pathological results, the patients were divided into pT1-2, pT3-4, pN0, and pN1-3 subgroups, with 148, 150, 135, and 163 cases, respectively. Progressive events and corresponding time were recorded during follow-up. DFS was defined as the time from radical operation to progressive events; if no progressive events occurred, DFS was defined as the time from radical operation to the last follow-up. The Kaplan-Meier curve and log-rank test were used to analyze the differences in cumulative DFS among patients with different CT imaging features, and Cox survival analysis was used to explore the independent CT imaging risk factors affecting DFS of cN0 patients. The log-rank test was used to test the effect of independent risk factors on cumulative DFS in different subgroups.Results:The follow-up time of enrolled patients was 36.0 (14.9, 59.3) months. The 3-year cumulative DFS rates of cT3-4 and cT1-2 GC patients were 61.2% and 85.6%, respectively, and the difference of DFS was statistically significant (χ 2=22.72, P<0.001). The 3-year cumulative DFS rate of EMVI-positive patients was 46.3%, which was lower than that of EMVI-negative patients (77.1%), and the difference was statistically significant (χ 2=21.34, P<0.001). There was no significant difference in 3-year cumulative DFS between different tumor locations and morphological types (χ 2=1.75, 1.73, P=0.189, 0.196). The difference in 3-year cumulative DFS between the tumor maximal diameter ≥3.4 cm and <3.4 cm groups was statistically significant (χ 2=17.58, P<0.001). On Cox survival analysis, cT (HR=5.203, P=0.001) and EMVI (HR=1.971, P=0.025) were independent risk factors for 3-year DFS in patients with cN0 GC. The results of subgroup analysis showed that the effect of EMVI on the 3-year DFS in pN0, pN1-3, pT1-2 and pT3-4 subgroups was statistically significant ( P<0.05). The effect of cT on the 3-year DFS was statistically significant in pN0, pN1-3, and pT1-2 subgroups ( P<0.05), but not in pT3-4 group (χ 2=2.58, P=0.108). Conclusion:cT and EMVI defined on preoperative CT examination are independently prognostic factors of 3-year DFS for patients with cN0 GC.

The PEPC family proteins are ubiquitous in various plants and play an important role in the process of photosynthetic carbon assimilation and have many non-photosynthetic biological functions. However, PEPC genes have not been reported in apple. In this study, the members of apple MdPEPC family were identified based on the new apple genome data by bioinformatics analysis, and their expression patterns in different tissues and the apple axillary bud transcriptome treated by decapitation and TDZ (cytokinin) were analyzed in order to explore the role of MdPEPC genes in apple axillary bud outgrowth. The results showed that 6 MdPEPC family members were identified in apple, which distributed on 6 different chromosomes, and had similar physicochemical characteristics. Phylogenetic tree and sequence alignment analysis showed that the MdPEPC could be divided into two subgroups (Group Ⅰ and Group Ⅱ), in which four members in MdPEPC family were clustered into Group Ⅰ, belonging to plant-type PEPCs. However, MdPEPC4 and MdPEPC5 were clustered into Group Ⅱ with AtPPC4, belonging to bacterial-type PEPCs. There were 7 pairs of fragments repeats among MdPEPC members, but no tandem repeats existed. The promoter cis-acting element analysis showed that MdPEPC genes were not only affected by light and stress, but also regulated by multiple hormones. The expression profiles showed that all MdPEPCs except MdPEPC4 and MdPEPC5 were expressed in different apple tissues. Transcriptome data analysis showed that the expression levels of MdPEPC1 and MdPEPC3 were up-regulated after decapitation and TDZ treatment, whereas MdPEPC2 was significantly down-regulated at 48 h after treatments. In conclusion, MdPEPC1, MdPEPC2 and MdPEPC3 were selected as the candidate genes involved in axillary bud outgrowth regulation for further study.
Malus/metabolism* ; Gene Expression Regulation, Plant ; Phylogeny ; Decapitation ; Family ; Plant Proteins/metabolism*

OBJECTIVETo explore the effects of acrylonitrile on T lymphocyte subsets, expression of toll-like receptor 4 and related cytokines in rats.

METHODSSixty-four Sprague-Dawley rats were randomly divided into 4 female groups and 4 male groups, and there were 8 rats in each group. Rats in each group were respectively given a single dose of 0, 5, 10 and 20 mg/kg acrylonitrile by gavage, once a day, 5 days a week, for 13 weeks. Blood and spleen T lymphocyte subsets was detected by flow cytometry, the mRNA expression of TLR4, IL-1β and TNF-α was analyzed by real-time quantitative PCR, the protein expression of TLR4 was evaluated by Western blot.

RESULTSCompared with control group, the percentages of blood CD3, CD4 T cells in 20 mg/kg female group and CD4/CD8 ratio in 5, 10 and 20 mg/kg female groups was significantly decreased, CD8 T cells in 20 mg/kg group was significantly increased (P < 0.05 or P < 0.01), blood CD3 T cells in 5 mg/kg male group, CD4 T cells and CD4/CD8 ratio in 20 mg/kg male groups were lower than that of control group, CD8 T cells in 20 mg/kg make group was significantly in oreased (P < 0.05 or P < 0.01). Spleen CD4, CD8 T lymphocyte percentages and CD4/CD8 ratio in 20 mg/kg female group decreased significantly, CD8 T cells in 20 mg/kg male group was significantly increased (P < 0.05 or P < 0.01), spleen CD3, CD4, CD8 T cells in 20 mg/kg male group and CD4/CD8 ratio in 10, 20 mg/kg male groups was also significantly decreased, CD3 T cells in 20 mg/kg and CD8 T cells in 10, 20 mg/kg male groups were significantly increased (P < 0.05 or P < 0.01) (TLR4 mRNA was lower expressed in 5, 10 and 20 mg/kg male groups and 10 mg/kg female group (P < 0.05 or P < 0.01), and TLR4 protein in 5 mg/kg female group and 20 mg/kg male group was significantly lower than control group (P < 0.05). The expression level of IL-1β mRNA was significantly decreased in 5, 10 and 20 mg/kg female group and 5, 10 mg/kg male group (P < 0.05 or P < 0.01), TNF-α mRNA was lower expressed in 10, 20 mg/kg female groups and 5, 10 mg/kg male groups (P < 0.01).

CONCLUSIONAcrylonitrile may lead to the changes of CD3, CD4, CD8 T lymphocyte percentages and CD4/CD8 ratio in rat blood and spleen, and also significantly effected the expression level of TLR4 mRNA and protein together with the secretion of IL-1β, TNF-α. This may cause effects on the cellular immune function.

Acrylonitrile ; toxicity ; Animals ; Female ; Interleukin-1beta ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; T-Lymphocyte Subsets ; drug effects ; immunology ; Toll-Like Receptor 4 ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism