KDM6B promotes ESCC cell proliferation and metastasis by facilitating C/EBPß transcription.

BACKGROUND: As an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression, KDM6B has been implicated in the development and malignant progression in various types of cancers. However, its potential roles in esophageal squamous cell carcinoma (ESCC) have not been explored. METHODS: The expression of KDM6B in human ESCC tissues and cell lines was examined using RT-qPCR, immunohistochemical staining and immunoblotting. The effects of KDM6B on the proliferation and metastasis of ESCC were examined using in vitro and in vivo functional tests. RNA-seq and ChIP-seq assay were used to demonstrate the molecular biological mechanism of KDM6B in ESCC. RESULTS: We show that the expression level of KDM6B increased significantly in patients with lymph node metastasis. Furthermore, we confirmed that KDM6B knockdown reduces proliferation and metastasis of ESCC cells, while KDM6B overexpression has the opposite effects. Mechanistically, KDM6B regulates TNFA_SIGNALING_VIA_NFκB signalling pathways, and H3K27me3 binds to the promoter region of C/EBPß, leading to the promotion of C/EBPß transcription. Besides, we show that GSK-J4, a chemical inhibitor of KDM6B, markedly inhibits proliferation and metastasis of ESCC cells. CONCLUSIONS: The present study demonstrated that KDM6B promotes ESCC progression by increasing the transcriptional activity of C/EBPß depending on its H3K27 demethylase activity.

Icaritin Inhibits Collagen Degradation-Related Factors and Facilitates Collagen Accumulation in Atherosclerotic Lesions: A Potential Action for Plaque Stabilization.

Most acute coronary syndromes result from rupture of vulnerable atherosclerotic plaques. The collagen content of plaques may critically affect plaque stability. This study tested whether Icaritin (ICT), an intestinal metabolite of Epimedium-derived flavonoids, could alter the collagen synthesis/degradation balance in atherosclerotic lesions. Rabbits were fed with an atherogenic diet for four months. Oral administration of ICT (10 mg·kg(-1)·day(-1)) was started after two months of an atherogenic diet and lasted for two months. The collagen degradation-related parameters, including macrophages accumulation, content and activity of interstitial collagenase-1 (MMP-1), and the collagen synthesis-related parameters, including amount and distribution of smooth muscle cells (SMC) and collagen mRNA/protein levels, were evaluated in the aorta. ICT reduced plasma lipid levels, inhibited macrophage accumulation, lowered MMP-1 mRNA and protein expression, and suppressed proteolytic activity of pro-MMP-1 and MMP-1 in the aorta. ICT changed the distribution of the SMCs towards the fibrous cap of lesions without increasing the amount of SMCs. Higher collagen protein content in lesions and aorta homogenates was observed with ICT treatment compared with the atherogenic diet only, without altered collagen mRNA level. These results suggest that ICT could inhibit the collagen degradation-related factors and facilitate collagen accumulation in atherosclerotic lesions, indicating a new potential of ICT in atherosclerotic plaques.

[Adsorption of Phosphate and Heavy Metals by Lanthanum Modified Zeolite and Its Performance in Sediment Inactivation].

Due to the large scale of mining and smelting activities, considerable amounts of heavy metals are discharged into the environment and accumulate in the sediment of rivers and lakes. The combined pollution of heavy metals and the intrinsic phosphorus in sediment calls for novel remediation technologies. In this study, lanthanum-modified zeolite (LMZ) was employed as an inactivation agent for the immobilization of phosphorus, zinc, and lead in sediments. The adsorption capacities as well as the inactivation performance of LMZ for P, Zn, and Pb were investigated, and the adsorption mechanisms were explored via desorption experiments, X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). The results indicated that the adsorption maximums of LMZ for P, Zn, and Pb were 53.76, 27.70, and 123.45 mg·g-1, respectively. Pre-adsorption of Zn and Pb had a negligible effect on the P adsorption by LMZ, whereas the adsorption of Zn and Pb were inhibited significantly by the pre-adsorption. P, Zn, and Pb in the sediment were transformed to more stable or less bioavailable forms by dosing 0.83% and 1.66% weight percentages of LMZ. It was found that P, Zn, and Pb were adsorbed through the formation of inner-sphere complexes. Further, desorption experiments and XRD patterns suggested that electrostatic attraction and surface precipitation also contributed to the adsorption of Zn and Pb, respectively.

[Molecular mechanism of effect of wenban humai granule on stability of atheromatous plaque].

OBJECTIVE: To explore the molecular mechanism of wenban humai granule (WHG) in stabilizing atheromatous plaque, by observing its effect on the collagen degradation and synthesis imbalance manner in the fibrous cap of the plaque. METHODS: Atherosclerosis (AS) rabbit model established by feeding high fat diet. The changes of protein and mRNA expression of macrophage CD68, metalloproteinase-1 (MMP-1), alpha-smooth muscle actin (alpha-SMA) and collagen I (C-I) in model rabbits' neo-genesic intima were determined by immunohistochemical stain and in situ hybridization methods before and after treatment as well as before and after modeling. RESULTS: After being fed with high fat diet for 7 weeks, the protein and mRNA expression of macrophage CD68, MMP-1 in neo-genesic intima of aorta in the model rabbits significantly increased, these changes could be significantly restored after 8 weeks treatment with WHG or simvastatin. At the same time, the expressions of alpha-SMA protein and C-I protein and mRNA slightly increased due to the immigration of SMC in aortic media to neo-genesic intima, these expressions could be further increased after WHG treatment but showed a reducing trend after simvastatin treatment (P < 0.05 and P < 0.01). In the whole course, positive correlation was shown between protein expressions of CD68 and MMP-1 (r = 0.952, P < 0.01) and also between these of alpha-SMA and C-I (r = 0.793, P < 0.01). CONCLUSION: WHG affects the collagen degradation and synthesis imbalance in the fibrous cap of the plaque to stabilize plaque through bi-directional regulation, up-regulating synthesis thesis factors and down-regulating degradation factors, while simvastatin perform its action on plaque stability by down-regulating degradation factors alone.

[Discussion about treatment of severe acute respiratory syndrome based on syndrome differentiation].

Severe acute respiratory syndrome is an infectious disease caused by a new type of coronavirus. It belongs to the seasonal febrile diseases in traditional Chinese medicine. The prevention and treatment of severe acute respiratory syndrome (SARS) can be under the guidance of the doctrines for treating febrile diseases of traditional Chinese medicine, treatment based on syndrome differentiation, such as syndrome differentiation of triple energizer, syndrome differentiation according to defensive phase, qi phase, nutrient phase and blood phase. During April and May of 2003, 8 cases of SARS were diagnosed in Shanghai, and 6 patients accepted complementary therapy of traditional Chinese medicine, without death case. The only one patient who didn't take glucocorticoid therapy was complementarily treated with traditional Chinese herbs through the whole treating procedure. Upon the successful treatment of the eight cases of SARS in Shanghai, it is demonstrated that the triple-energizer syndrome differentiation and defensive-qi-nutrient-blood syndrome differentiation in traditional Chinese medicine are of high value in treating SARS patients.

Effect of Lianshu preparation on lipopolysaccharide-induced diarrhea in rats.

AIM: To investigate the effect of Lianshu preparation on lipopolysaccharide (LPS)-induced diarrhea in rats. METHODS: A diarrhea model was established in Sprague Dawley rats via injection of 1 mL of 30 mg/kg LPS. A total of 40 rats were randomly divided into normal group, LPS group, LPS + Lianshu group, LPS + berberine group (n = 10 in each group). Their intestinal mucosal barrier and frequency of diarrhea were observed. Levels of glucose, serum Na(+), K(+), Cl(-) and hematocrit, plasma nitrogen monoxide (NO), diamine oxidase (DAO), and D (-)-lactate were measured. The number of IgA+ plasma cells in small intestine was detected and SIgA levels in the intestinal fluid were measured. The antipyretic activity of Lianshu preparation in rats was evaluated using Brewer's yeast-induced pyrexia (10 mL/kg of 20% aqueous suspension). Acetaminophen (250 mg/kg, intragastric administration, bid) was used as a standard drug for comparison. Temperature was recorded 1 h before and 6 h after Brewer's yeast injection. Finally, small intestinal transmission in mice treated with Lianshu was detected after intraperitoneal injection of methyl prostigmin (2 mg/kg). Atropine (10 g/kg) was used as a control. The ink content in intestine was determined and the total length of intestine was measured. RESULTS: The frequency of diarrhea was higher in LPS group than in LPS + Lianshu group and LPS + berberine group (36.70 +/- 5.23 vs 28.50 +/- 4.06 and 32.70 +/- 9.30 respectively, P < 0.01), and lower in LPS + Lianshu group than in LPS + berberine group (P = 0.03). The levels of Na(+), glucose, Cl(-), K(+) were significantly lower in LPS + Lianshu group than in LPS + berberine group (140.35 +/- 3.19 mmol/L vs 131.99 +/- 4.86 mmol/L, 8.49 +/- 1.84 mmol/L vs 6.54 +/- 2.30 mmol/L, 106.29 +/- 4.41 mmol/L vs 102.5 +/- 1.39 mmol/L, 5.08 +/- 0.66 mmol/L vs 4.32 +/- 0.62 mmol/L respectively, P < 0.05). The level of hematocrit was lower in LPS + Lianshu group than in LPS + berberine group (0.50% +/- 0.07% vs 0.59% +/- 0.10% respectively, P < 0.05). The plasma levels of NO, DAO and D (-)-lactate were higher in LPS group than in normal group (79.74 +/- 7.39 micromol/L vs 24.94 +/- 3.38 micromol/L, 2.48 +/- 0.42 micro/mL vs 0.82 +/- 0.33 micro/mL, 5.63 +/- 0.85 microg/mL vs 2.01 +/- 0.32 microg/mL respectively, P < 0.01), and lower in LPS + Lianshu group than in LPS + berberine group (48.59 +/- 4.70 micromol/L vs 51.56 +/- 8.38 micromol/L, 1.43 +/- 0.53 micromol/mL vs 1.81 +/- 0.42 micromol/mL, 4.00 +/- 0.54 microg/mL vs 4.88 +/- 0.77 microg/mL respectively, P < 0.05). The morphology of the intestinal mucosa showed destroyed villi in LPS group and atrophied intestinal mucosa in other groups. The pathological intestinal mucosal changes were less in LPS + Lianshu group than in LPS group. The number of IgA+ plasma cells and amount of SIgA were higher in LPS + Lianshu group than in LPS group (1.16 +/- 0.19/microm(2) vs 1.09 +/- 0.28/microm(2), P = 0.026; 0.59 +/- 0.12 mg/L vs 0.15 +/- 0.19 mg/L respectively, P = 0.000). Lianshu had counteractive effects on yeast-induced pyrexia and enterokinesia in rats. CONCLUSION: Lianshu preparation has therapeutic effects on LPS-induced diarrhea and enterokinesia in rats.