Naoluo Xintong Decoction activates caspase-1/Gasdermin D pathway to promote angiogenesis of rat brain microvascular endothelial cells after oxygen glucose deprivation/reperfusion injury / 南方医科大学学报

OBJECTIVE@#To investigate the effects of Naoluo Xintong Decoction (NLXTD) on pyroptosis and angiogenesis of brain microvascular endothelial cells (BMECs) and explore the possible mechanisms in rats with oxygen-glucose deprivation/ reperfusion (OGD/R).@*METHODS@#Rat BMECs with or without caspase-1 siRNA transfection were cultured in the presence of 10% medicated serum from NLXTD-treated rats (or blank serum) and exposed to OGD/R. CCK-8 assay, Transwell chamber assay, and tube formation assay were used to assess proliferation, migration, and tube-forming abilities of the cells. The activity of lactate dehydrogenase (LDH) in the culture supernatant was determined using a commercial assay kit, and the levels of inflammatory factors IL-1β and IL-18 were detected with ELISA. The cellular expressions of pro-caspase-1, caspase-1, NLRP3, Gasdermin D, and angiogenesis-related proteins VEGF and VEGFR2 were detected using Western blotting.@*RESULTS@#The BMECs showed obvious injuries after OGD/R exposure. Compared with the blank serum, the medicated serum significantly improved the cell viability, migration ability, and lumen-forming ability (P < 0.01) and lowered the levels of IL-1β and IL-18 and the LDH release (P < 0.01) of the cells with OGD/R exposure. Western blotting showed that in the BMECs exposed to OGD/R, the medicated serum strongly upregulated the expression of VEGF and VEGFR2 proteins (P < 0.01) and reduced the protein expressions of pro-caspase-1, caspase-1, NLRP3, and Gasdermin D (P < 0.01), and transfection of the cells with caspase-1 siRNA further promoted the expressions of VEGFR2 protein in the cells (P < 0.01).@*CONCLUSION@#NLXTD can improve the proliferation, migration, and tube- forming ability and promote angiogenesis of BMECs with OGD/R injury probably by inhibiting the caspase-1/Gasdermin D pathway in pyroptosis, alleviating cell injury, and upregulating the expressions of VEGF and VEGFR2.

Intervention Effect of Gandou Fumu Decoction on Renal Fibrosis in TX Mice Through JAK/STAT Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the protective effect and underlying mechanism of Gandou Fumu decoction （GDFMT） on renal fibrosis in a mouse model of Wilson's disease. MethodSixty adult male toxic milk （TX） mice were randomly divided into a model group， high-， medium-， and low-dose GDFMT groups， and a positive control （penicillamine） group， and another 12 wild-type mice were assigned to the normal group. The high-， medium-， and low-dose GDFMT groups were administered GDFMT at 13.92， 6.96， 3.48 g·kg-1， respectively， and the positive control group received penicillamine at 0.1 g·kg-1， while the model and normal groups were given an equal volume of 0.9% saline solution by gavage once a day for 4 consecutive weeks. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of blood urea nitrogen （BUN）， creatinine （CRE）， type Ⅲ procollagen （PC-Ⅲ）， and type Ⅳ collagen （C-Ⅳ） in the serum. Histological changes in the mouse kidneys were examined by hematoxylin-eosin （HE） and Masson's trichrome staining. Immunofluorescence was used to assess the protein expression of leptin， Janus kinase 2 （JAK2）， and signal transducer and activator of transcription （STAT） in renal cells. Real-time polymerase chain reaction （Real-time PCR） was performed to analyze the mRNA expression levels of leptin， leptin receptor（OB-R）， JAK2， and STAT. Western blot was used to detect the expression of transforming growth factor-β1 （TGF-β1） and monocyte chemoattractant protein-1 （MCP-1）. ResultCompared with the normal group， the model mice exhibited a significant increase in BUN， CRE， PC-Ⅲ， and C-Ⅳ levels （P<0.01）. Compared with the model group， the high- and medium-dose GDFMT groups and the penicillamine groups showed significant decreases in these parameters （P<0.05， P<0.01）， with the high-dose GDFMT group demonstrating the most significant reduction （P<0.01）. The histological examination of renal tissue revealed fibrosis in the model group， while the fibrotic damage was mitigated to varying degrees after drug intervention， with improvement in fibrosis. Immunofluorescence results showed that leptin， JAK2， and STAT3 protein expression levels were significantly upregulated in the renal fibrosis of the model group. After GDFMT intervention， the fluorescence intensity decreased， with the high-dose GDFMT group showing the lowest intensity. Real-time PCR results demonstrated that leptin， OB-R， JAK2， and STAT3 mRNA expression levels were significantly elevated in the model group compared with those in the normal group， while the high- and medium-dose GDFMT groups and the penicillamine group showed significant reductions in their expression levels （P<0.05， P<0.01）. Western blot analysis revealed that TGF-β1 and MCP-1 expression levels were significantly increased in the model group （P<0.01）， and the high- and medium-dose GDFMT groups exhibited significant reductions in their expression levels （P<0.01）. ConclusionGDFMT can alleviate renal fibrosis damage in TX mice， and its mechanism of action may be related to the regulation of leptin and the JAK/STAT signaling pathway.

Mechanism of long non-coding RNA in prostate cancer / 国际肿瘤学杂志

Long non-coding RNA (lncRNA) is a type of RNA molecule whose transcript is longer than 200 nucleotides and cannot encode protein. Studies in recent years have shown that lncRNA plays an important role in the physiological and pathological processes of the body. It participates in the occurrence, development and metastasis of prostate cancer. Further study on the role and mechanism of lncRNA in prostate cancer is expected to provide new ideas for the diagnosis and treatment of prostate cancer.

Effect of Loureirin A on Proliferation and Frizzled-4 Expression of Rat Hepatic Stellate Cells in vitro / 昆明医科大学学报

Objective To investigate the molecular mechanism of Loureirin A mediated anti-hepatic fibrosis by evaluting its effects on proliferation , secretion ofα-smooth muscle actin (α-SMA) and transforming growth factor-beta1 (TGF-β1), and expression of rat hepatic stellate cells in vitro . Methods Primary hepatic stellate cells were isolated and cultured from Sprague-Dawley rats. After activating and inducing primary hepatic stellate cells from qHSC to aHSC, the activated hepatic stellate cells model in vitro was established. Then we observed the morphological changes of static hepatic stellate cells and activated hepatic stellate cells with inverted phase contrast microscope. Cultured hepatic stellate cells were treated with different concentrations of loureirin A and the inhibitory rate of HSCs proliferation was measured by MTT assay. The expression of Frizzled-4 was measured by western blot analysis. The content ofα-SMA and TGF-β1 in the cultured HSCs'supernatant were measured by enzyme-linked immunosorbent assay (ELISA) . Results Loureirin A the proliferation of inhibited activated hepatic stellate cells in a time-dose-dependent manner compared with the control group,IC50=0.30 μg/μL. After loureirinA treatment of the HSCs, western blot analysis showed that Frizzled-4 expression level was obviously lower than control group. Loureirin A also inhibitedα-SMA and TGFβ1 (P<0.05) secretion in the cultured HSCs'supernatant in different degree by the assay of ELISA. Conclusions The molecular mechanism of Loureirin A and Wnt signaling pathway mediated anti-hepatic fibrosis and anti-angiogenesis may involve down-regulation the expression of Frizzled-4, inhibiting the synthesis and secretion ofα-SMA,TGF-β1and the proliferation of HSCs.

Establishment and evaluation of a rat model of ulcerative colitis with syndrome of dampness stagnancy due to spleen deficiency / 中西医结合学报

To establish a rat model of ulcerative colitis with syndrome of spleen deficiency and dampness stagnancy.

Expression of Merlin protein in non-small cell lung carcinoma and the clinical significance / 中南大学学报(医学版)

OBJECTIVE@#To determine the expression and clinical significance of Merlin protein in non-small cell lung cancer (NSCLC).@*METHODS@#The expression of Merlin protein in 45 cases of NSCLC and adjacent tissue of NSCLC and normal lung tissue was checked by immunohistochemistry. The relation between the expression of Merlin protein and the multiple factors of pathological type, gender, P-TNM stage, differentiation and lymph node metastasis was analyzed.@*RESULTS@#The expression rates of Merlin protein in NSCLC and normal lung tissue sections were 73.33% and 15.56%, respectively (P0.05).@*CONCLUSION@#Merlin protein might contribute to the initiation of metastasis of NSCLC.

Effects of two kinds of Chinese medicine compound on expression of Notch-1 and Jagged1 in ischemic penumbra after local cerebral ischemia/reperfusion in MCAO rats / 中国病理生理杂志

AIM: To investigate the effects of Yiqi Huoxue prescription and Bushen Shengsui prescription on the expression of Notch-1 and Jagged1 protein in ischemic penumbra after local cerebral ischemia/reperfusion in intraluminal thread occlusion of the middle cerebral artery (MCAO) rats. METHODS: The local cerebral ischemia/reperfusion model was established by intraluminal thread occlusion of the middle cerebral artery. The animals were randomly divided into pseudo surgery group (sham group), model (MCAO) group, Yiqi Huoxue prescription (MCAO+Yiqi Huoxue) and Bushen Shengsui prescription (MCAO+Bushen Shengsui) groups. Using the techniques of immuno-histochemical staining, the expression of Notch-1 and Jagged1 was observed at 1, 2 and 3 weeks in ischemic penumbra of the cortex of frontal and parietal lobe. RESULTS: A value and positive unit of Notch-1 and Jagged1 protein expression in model group were higher than those in sham in ischemic penumbra of the cortex of frontal or parietal lobe after local cerebral ischemia/reperfusion in MCAO rats (P<0.05 or P<0.01). A value and/or positive unit of the expression in Yiqi Huoxue prescription and Bushen Shengsui prescription groups were lower than those in model group (P<0.05 or P<0.01). CONCLUSION: Yiqi Huoxue prescription and Bushen Shengsui prescription affect the proliferation and differentiation of neural stem cells, depress Notch signal transduction after local cerebral ischemia/reperfusion in MCAO rats by inhibiting the expression of Notch-1and Jagged1 protein.

Oncolytic adenovirus in tumor targeted therapy / 国际肿瘤学杂志

Oncolytic adenovirus is known to carry out the transformation of adenovirus,which has kill-ing role on tumor defective gene phenotypes,and Can be used as vector for tumor targeted tbempy drugs.At pres-ent,H101 and dl1520 and other biological products are gained from adenovirus type 5-specific gene fragments,which targeted tumor cell defects in the p53 gene expression,can specifically recognize tumor cells and Carry out proliferation and lysis of tumor cells.These biological products can be used as vectors to carry the anti-tumor genes and result in more powerful anti-tumor effects.

Relationship between morphologic changes in neuron or neuroglial cells and expression of TNF-? and c-Myc in cortex after focal cerebral ischemia/reperfusion in MCAO rats / 中国病理生理杂志

AIM: To investigate the relationship between morphologic changes in neuron or neuroglial cells and expression of tumor necrosis factor ? (TNF-?) and c-Myc in cortex after focal cerebral ischemia/reperfusion in MCAO rats. METHODS: The focal cerebral ischemia/reperfusion model was established by intraluminal thread occlusion of the middle cerebral artery (MCAO). The middle cerebral arteries of rats were occluded for 2 hours and reperfused for 1, 3 and 7 days. Using the techniques of immunohistochemical staining and optical microscopy, the morphologic changes in neuron or neuroglial cells were observed in the cortex of frontal or parietal lobe; the cell types which dynamicaly expressed TNF-?, c-Myc in the different period were also observed. RESULTS: The degeneration or necrosis of neuron or neuroglial cells were observed at the center of infarction, it was very serious at 3 d after reperfussion. Astrocyte and microglial cell proliferation were observed at the broder of infarction. TNF-? and c-Myc positive cells, most of which were astrocytes and microglial cells, increased significantly at 3 d after reperfusion. CONCLUSION: TNF-? and c-Myc may play an important role in the regulation of neuron or neuroglial cells after focal cerebral ischemia with reperfusion. [