BMI-1 activates hepatic stellate cells to promote the epithelialmesenchymal transition of colorectal cancer cells

BACKGROUND Activated hepatic stellate cells(aHSCs)are the major source of cancer-associated fibroblasts in the liver.Although the crosstalk between aHSCs and colorectal cancer(CRC)cells supports liver metastasis(LM),the mechanisms are largely unknown.AIM To explore the role of BMI-1,a polycomb group protein family member,which is highly expressed in LM,and the interaction between aHSCs and CRC cells in promoting CRC liver metastasis(CRLM).METHODS Immunohistochemistry was carried out to examine BMI-1 expression in LM and matched liver specimens of CRC.The expression levels of BMI-1 in mouse liver during CRLM(0,7,14,21,and 28 d)were detected by Western blotting(WB)and the quantitative polymerase chain reaction(qPCR)assay.We overexpressed BMI-1 in HSCs(LX2)by lentivirus infection and tested the molecular markers of aHSCs by WB,qPCR,and the immunofluorescence assay.CRC cells(HCT116 and DLD1)were cultured in HSC-conditioned medium(LX2 NC CM or LX2 BMI-1 CM).CM-induced CRC cell proliferation,migration,epithelial-mesenchymal transition(EMT)phenotype,and transforming growth factor beta(TGF-β)/SMAD pathway changes were investigated in vitro.A mouse subcutaneous xenotransplantation tumor model was established by co-implantation of HSCs(LX2 NC or LX2 BMI-1)and CRC cells to investigate the effects of HSCs on tumor growth and the EMT phenotype in vivo.RESULTS Positive of BMI-1 expression in the liver of CRLM patients was 77.8%.The expression level of BMI-1 continued to increase during CRLM in mouse liver cells.LX2 overexpressed BMI-1 was activated,accompanied by increased expression level of alpha smooth muscle actin,fibronectin,TGF-β1,matrix metalloproteinases,and interleukin 6.CRC cells cultured in BMI-1 CM exhibited enhanced proliferation and migration ability,EMT phenotype and activation of the TGF-β/SMAD pathway.In addition,the TGF-βR inhibitor SB-505124 diminished the effect of BMI-1 CM on SMAD2/3 phosphorylation in CRC cells.Furthermore,BMI-1 overexpressed LX2 HSCs promoted tumor growth and the EMT phenotype in vivo.CONCLUSION High expression of BMI-1 in liver cells is associated with CRLM progression.BMI-1 activates HSCs to secrete factors to form a prometastatic environment in the liver,and aHSCs promote proliferation,migration,and the EMT in CRC cells partially through the TGF-β/SMAD pathway.

Therapeutic effect of Qingyi decoction in severe acute pancreatitis-induced intestinal barrier injury

AIM: To investigate the effect of Qingyi decoction onthe expression of secreted phospholipase A2(s PLA2) in intestinal barrier injury.METHODS: Fifty healthy Sprague-Dawley rats were randomly divided into control, severe acute pancreatitis(SAP), Qingyi decoction-treated(QYT), dexamethasonetreated(DEX), and verapamil-treated(VER) groups. The SAP model was induced by retrograde infusion of 1.5% sodium deoxycholate into the biliopancreatic duct of the rats. All rats were sacrificed 24 h post-SAP induction. Arterial blood, intestine, and pancreas from each rat were harvested for investigations. The levels of serum amylase(AMY) and diamine oxidase(DAO) were determined using biochemical methods, and serum tumor necrosis factor(TNF)-α level was measured by an enzyme linked immunosorbent assay. Pathologic changes in the harvested tissues were investigated by microscopic examination of hematoxylin and eosinstained tissue sections. The expressions of s PLA2 at m RNA and protein levels were detected by reverse transcriptase PCR and Western blot, respectively. A terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling assay was used to investigate apoptosis of epithelial cells in the intestinal tissues. RESULTS: Compared to the control group, the expression of s PLA2 at both the m RNA and protein levels increased significantly in the SAP group(0.36 ± 0.13 vs 0.90 ± 0.38, and 0.16 ± 0.05 vs 0.64 ± 0.05, respectively; P s < 0.01). The levels of AMY, TNF-α and DAO in serum were also significantly increased(917 ± 62 U/L vs 6870 ± 810 U/L, 59.7 ± 14.3 ng/L vs 180.5 ± 20.1 ng/L, and 10.37 ± 2.44 U/L vs 37.89 ± 5.86 U/L, respectively; P s < 0.01). The apoptosis index of intestinal epithelial cells also differed significantly between the SAP and control rats(0.05 ± 0.02 vs 0.26 ± 0.06; P < 0.01). The serum levels of DAO and TNF-α, and the intestinal apoptosis index significantly correlated with s PLA2 expression in the intestine(r = 0.895, 0.893 and 0.926, respectively; Ps < 0.05). Thelevels of s PLA2, AMY, TNF-α, and DAO in the QYT, VER, and DEX groups were all decreased compared with the SAP group, but not the control group. Qingyi decoction intervention, however, gave the most therapeutic effect against intestinal barrier damage, although the onset of its therapeutic effect was slower. CONCLUSION: Qingyi decoction ameliorates acute pancreatitis-induced intestinal barrier injury by inhibiting the overexpression of intestinal s PLA2. This mechanism may be similar to that of verapamil.

Qingyi decoction attenuates intestinal epithelial cell injury via the calcineurin/nuclear factor of activated T-cells pathway

BACKGROUND Recent studies have demonstrated that dysfunction of the intestinal barrier is a significant contributing factor to the development of severe acute pancreatitis(SAP).A stable intestinal mucosa barrier functions as a major anatomic and functional barrier,owing to the balance between intestinal epithelial cell(IEC)proliferation and apoptosis.There is some evidence that calcium overload may trigger IEC apoptosis and that calcineurin(CaN)/nuclear factor of activated Tcells(NFAT)signaling might play an important role in calcium-mediated apoptosis.AIM To investigate the potential mechanisms underlying the therapeutic effect of Qingyi decoction(QYD)in SAP.METHODS A rat model of SAP was created via retrograde infusion of sodium deoxycholate.Serum levels of amylase,tumor necrosis factor(TNF-α),interleukin(IL)-6,D-lactic acid,and diamine oxidase(DAO);histological changes;and apoptosis of IECs were examined in rats with or without QYD treatment.The expression of the two subunits of CaN and NFAT in intestinal tissue was measured via quantitative realtime polymerase chain reaction and western blotting.For in vitro studies,Caco-2 cells were treated with lipopolysaccharide(LPS)and QYD serum,and then cell viability and intracellular calcium levels were detected.RESULTS Retrograde infusion of sodium deoxycholate increased the severity of pancreatic and intestinal pathology and the levels of serum amylase,TNF-α,and IL-6.Both the indicators of intestinal mucosa damage(D-lactic acid and DAO)and the levels of IEC apoptosis were elevated in the SAP group.QYD treatment reduced the serum levels of amylase,TNF-α,IL-6,D-lactic acid,and DAO and attenuated the histological findings.IEC apoptosis associated with SAP was ameliorated under QYD treatment.In addition,the protein expression levels of the two subunits of CaN were remarkably elevated in the SAP group,and the NFATc3 gene was significantly upregulated at both the transcript and protein levels in the SAP group compared with the control group.QYD significantly restrained CaN and NFATc3 gene expression in the intestine,which was upregulated in the SAP group.Furthermore,QYD serum significantly decreased the LPS-induced elevation in intracellular free Ca^(2+)levels and inhibited cell death.CONCLUSION QYD can exert protective effects against intestinal mucosa damage caused by SAP and the protective effects are mediated,at least partially,by restraining IEC apoptosis via the CaN/NFATc3 pathway.

Isolated splenic metastases from gastric carcinoma:A case report and literature review

Isolated metastases to the spleen from gastric carcinoma is very rare.Only a few cases have been reported in the literature.We herein present a case of isolated splenic metastases in a 62-year-old man,occurring 12 mo after total gastrectomy for gastric carcinoma.The patient underwent a laparoscopic exploration,during which two lesions were found at the upper pole of the spleen,without involvement of other organs.A laparoscopic splenectomy was performed.Histological examination confirmed that the splenic tumor was a poorly differentiated adenocarcinoma similar to the primary gastric lesion.The postoperative course was uneventful and the patient has been well for 9 mo,with no tumor recurrence.The clinical data of 18 cases of isolated splenic metastases from gastric carcinoma treated by splenectomy were summarized after a literature review.To our knowledge,this is the first reported case of isolated splenic metastases undergoing laparoscopic splenectomy.

Heralded entanglement purification protocol using high-fidelity parity-check gate based on nitrogen-vacancy center in optical cavity

The decoherence of entangled states caused by the noisy channel is a salient problem for reducing the fidelity of quantum communication.Here we present a heralded two-photon entanglement purification protocol(EPP)using heralded high-fidelity parity-check gate(HH-PCG),which can increase the entanglement of nonlocal two-photon polarization mixed state.The HH-PCG is constructed by the input-output process of nitrogen-vacancy(NV)center in diamond embedded in a single-sided optical cavity,where the errors caused by the imperfect interaction between the NV center-cavity system and the photon can be heralded by the photon detector.As the unwanted components can be filtrated due to the heralded function,the fidelity of the EPP scheme can be enhanced considerably,which will increase the fidelity of quantum communication processing.