Establishment and evaluation of pre-metastatic niche mouse model labelled with luciferase in lewis lung cancer cells / 细胞与分子免疫学杂志

Objective This study aimed to establish a pre-metastatic niche mouse model utilizing luciferase-labeled Lewis (Luc-Lewis) lung cancer cells and to assess the efficacy of this model employing both qualitative and quantitative methods. Methods C57BL/6 mice were categorized into two groups: a normal control group and a model group, each containing 15 individual mice. The pre-metastatic niche model was established via tail vein injection of Luc-Lewis lung cancer cells. Body mass were measured daily for all groups. Tumor fluorescence signals within the mice were detected using a high-throughput enzyme marker instrument. Lung tissue specimens were harvested to evaluate metastatic progression. HE staining was used to assess histopathological changes. Real-time quantitative PCR and Western blot analysis were used to detect the mRNA and protein expression of lysyl oxidase (LOX), matrix metalloproteinase 9 (MMP9), versican (VCAN), and fibronectin (FN), which are the specific markers for the formation of the microenvironment of lung tissues before metastasis. Results Significant declines in body mass and observable lethargy were noted in the model group when compared to the control group. Distinct fluorescence signals were observed in the lung tissue of the model group, demonstrating a positive correlation with the duration of model establishment. By day 14, elevated mRNA and protein expression levels of LOX, MMP9, VCAN, and FN were significantly evident. In addition, histopathological evaluations revealed augmented interstitial thickness, alveolar atrophy and significant inflammatory cell infiltration within the lung tissues of the model group. By the 21st day, metastatic lesions manifested in the lung tissues of the model group, suggesting an approximate pre-metastatic niche maturation timeline of 14 days. Conclusion A pre-metastatic niche mouse model for Lewis lung cancer is successfully established.

Regional Brain Activity During Rest and Gastric Water Load in Subtypes of Functional Dyspepsia: A Preliminary Brain Functional Magnetic Resonance Imaging Study

BACKGROUND/AIMS: Functional dyspepsia (FD) remains a great clinical challenge since the FD subtypes, defined by Rome III classification, still have heterogeneous pathogenesis. Previous studies have shown notable differences in visceral sensation processing in the CNS in FD compared to healthy subjects (HS). However, the role of CNS in the pathogenesis of each FD subtype has not been recognized. METHODS: Twenty-eight FD patients, including 10 epigastric pain syndrome (EPS), 9 postprandial distress syndrome (PDS), and 9 mixed-type, and 10 HS, were enrolled. All subjects underwent a proximal gastric perfusion water load test and the regional brain activities during resting state and water load test were investigated by functional magnetic resonance imaging. RESULTS: For regional brain activities during the resting state and water load test, each FD subtype was significantly different from HS (P < 0.05). Focusing on EPS and PDS, the regional brain activities of EPS were stronger than PDS in the left paracentral lobule, right inferior frontal gyrus pars opercularis, postcentral gyrus, precuneus, insula, parahippocampal gyrus, caudate nucleus, and bilateral cingulate cortices at the resting state (P < 0.05), and stronger than PDS in the left inferior temporal and fusiform gyri during the water load test (P < 0.05). CONCLUSIONS: Compared to HS, FD subtypes had different regional brain activities at rest and during water load test, whereby the differences displayed distinct manifestations for each subtype. Compared to PDS, EPS presented more significant differences from HS at rest, suggesting that the abnormality of central visceral pain processing could be one of the main pathogenesis mechanisms for EPS.

Levels of autophagy in T cells and B cell of patients with systemic lupus erythe-matosus and its clinical significance / 中国免疫学杂志

Objective:To investigate levels of autophagy in T cells and B cell of patients with systemic lupus erythematosus ( SLE) and its clinical significance.Methods: 68 SLE patients without treatment within 4 weeks were enrolled in this study.We accessed the levels of autophagy in T cells and B cells of 23 healthy controls and 68 patients before and after treatment by flow cytometry,and analyzed their correlations with serum levels of C3 and anti-dsDNA antibodies,SLEDAI score,et al.Results: Before treatment,a significantly increased levels of LC3-Ⅱ was observed in SLE patients than healthy controls, the active group ( SLEDAI score≥10) was significantly higher than the stable group(SLEDAI score0.05 ) . Conclusion:Levels of autophagy in T and B lymphocytes of SLE patients are abnormal compared to healthy controls,and these changes are associated with disease activity.Also,these changes are expected to be the indicators of disease activity and potential therapeutic targets in SLE.

Effects of Astragalus polysaccharide (APS) on cytokine and immune function impairment induced by cisplatin in mice bearing Lewis lung cancer / 中国实验动物学报

Objective To observe the effects of Astragalus polysaccharide ( APS) on tumor growth, cytokine and immune function impairment induced by cisplatin ( DDP) in mice bearing Lewis lung cancer.Methods A total of 90 mice were used in this study:10 for blank control group, and 80 mice with transplanted Lewis lung cancer were randomly divided into 8 groups:model control group (physiological saline), positive control group treated with DDP (6 mg/kg), low dose APS (50 mg/kg), moderate dose APS (100 mg/kg) and high dose APS (200 mg/kg) groups and three combinations of APS+DDP groups ( the same three APS levels with half dose of DDP, respectively) .0.3 mL of the drugs was intraper-itoneally injected to the mice, respectively, on the second day after moldeling.DDP was injected once a week and other drugs were injected once per day for consecutive 20 days.On the 21st day, blood samples were collected and serum levels of cytokine IL-2, IL-6, IL-12 and TNF-αwere determined by ELISA, and the tumor inhibition rate and immune organ in-dexes were assessed.Results The tumor inhibition rates of the positive control, low, moderate and high dose APS groups and three combinations of APS+DDP groups of mice bearing Lewis lung carcinoma were 49.30%, 17.21%, 39.68%, 17.21%, 51.02%, 57.21%and 65.11%, respectively.Compared with the model group, P<0.05 or P<0.01, and compared the three combination groups with the DDP group, P<0.05.Compared with the blank control group, the spleen index was significantly increased in the moderate and high dose APS groups and the three combinations of APS +DDP groups.There was a significant difference between the spleen indexes of the model control group, and the spleen indexes of high dose APS and the combination with high dose APS groups were significantly higher than that of the model control group (P<0.05).Compared with the DDP group, APS in various doses and combinations increased the thymus index and spleen index.Conclusions APS can improve the levels of cytokine IL -2, IL-6, IL-12 and TNF-αin mice bearing Lewis lung cancer, enhance the immune function impairment induced by DDP, has certain protective effect on the immune organs, and inhibit the growth of Lewis lung cancer in mice.When APS is used in combination with a half-dose of DDP, APS enhanced the inhibition of tumor growth.This mechanism may be related to the enhanced body immune function.Our results indicate that APS enhances the therapeutic effect of DDP and reduces its toxicity, therefore, may have potential application value in future treatment of solid tumors.