Study on the mechanism of magnesium calcium alloys/mineralized collagen composites mediating macrophage polarization to promote bone repair.

Magnesium-based composites are a focal point in biomaterials research. However, the rapid degradation rate of magnesium alloys does not align with the healing time of bone tissue. Additionally, the host reaction caused by magnesium implantation hampers its full osteogenic potential. To maintain an appropriate microenvironment, it is important to enhance both corrosion resistance and osteogenic activity of the magnesium matrix. In this study, a composite scaffold composed of mineralized collagen and magnesium alloy was utilized to investigate the regulatory effect of mineralized collagen on mouse macrophages and evaluate its impact on mouse bone marrow mesenchymal stem cells in terms of osteogenesis, immune response, and macrophage-induced osteogenic differentiation. This experiment examined the biocompatibility of mouse bone marrow mesenchymal stem cells and macrophage-induced osteogenic differentiation in vitro, and examined the expression levels of relevant pathways proteins. Magnesium calcium alloys/mineralized collagen exhibited extensive spreading, facilitated by broad and abundant pseudopodia that firmly adhered them to the material surface and promoted growth and pseudopodia formation. The findings revealed that magnesium calcium alloy/mineralized collagen scaffold materials induced osteogenic differentiation mainly through M2 polarization of macrophages. This effect was mainly mediated by promoting the integrin α2ß1-FAK-ERK1/2 signaling pathways and inhibiting the RANK signaling pathways.

AQP3 Promotes the Invasion and Metastasis in Cervical Cancer by Regulating NOX4-derived H2O2 Activation of Syk/PI3K/Akt Signaling Axis.

Unrestrained chronic inflammation leads to the abnormal activity of NOX4 and the subsequent production of excessive hydrogen peroxide (H2O2). Excessive H2O2 signaling triggered by prolonged inflammation is thought to be one of the important reasons for the progression of some types of cancer including cervical cancer. Aquaporin 3 (AQP3) is a member of the water channel protein family, and it remains unknown whether AQP3 can regulate the transmembrane transport of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4)-derived H2O2 induced by the stimulation of inflammatory factors to facilitate the malignant progression in cervical cancer. In this study, cervical cancer HeLa cell line was respectively treated with diphenyleneiodonium (DPI), N-Acetylcysteine (NAC) or lentivirus-shRNA- AQP3. Plate cloning, cell migration or transwell invasion assays, etc. were performed to detect the invasive and migration ability of the cells. Western blot and CO-IP were used to analyze the mechanism of AQP3 regulating H2O2 conduction. Finally, in vivo assays were performed for validation in nude mice. AQP3 Knockdown, DPI or NAC treatments all reduced intracellular H2O2 influx, and the activation of Syk/PI3K/Akt signal axis was inhibited, the migration and invasive ability of the cells was attenuated. In vivo assays confirmed that the excessive H2O2 transport through AQP3 enhanced the infiltration and metastasis of cervical cancer. These results suggest that AQP3 activates H2O2/Syk/PI3K/Akt signaling axis through regulating NOX4-derived H2O2 transport to contribute to the progression of cervical cancer, and AQP3 may be a potential target for the clinical treatment of advanced cervical cancer.

Effect of Heat Input on the Microstructure and Mechanical Properties of Local Dry Underwater Welded Duplex Stainless Steel.

Duplex stainless steel welded metals were underwater local dry prepared on S32101 lean duplex stainless steel trapezoidal groove plates with a self-made drain cover employing Supercore 2205P flux-cored filler wire. Different heat inputs were employed to investigate the effects on mechanical characteristics and the microstructure of welded metals. The results demonstrated that as the heat was applied, austenite concentrations in the weld metals increased. It was found that the austenite concentration and the fraction of Σ3-austenite twin-grain boundaries followed the same trends. With increasing heat input, the recrystallized ferrite and austenite grains initially decreased and subsequently increased, whereas the fraction of interphase boundaries between special ferrite and austenite exhibited the reverse trend. With a heat input of 1.4 kJ/mm, the toughness and plasticity of the weld metals were enhanced by an increase in austenite content, Σ3 recrystallized grains, and austenite twin-grain boundaries. The plasticity and tensile strength values of the welded metal changed more when the heat input was raised from 1.0 to 1.2 kJ/mm than when it was raised from 1.2 to 1.4 kJ/mm. Considering energy conservation, it is recommended to adopt 1.2 kJ/mm for welding heat input.

Combined treatment of marizomib and cisplatin modulates cervical cancer growth and invasion and enhances antitumor potential in vitro and in vivo.

Proteasome inhibition is an attractive approach for anticancer therapy. Cisplatin (cis-diamminedichloroplatinum, CDDP) is widely used as a standard chemotherapy drug in the treatment of solid malignant tumors, such as cervical cancer, ovarian cancer, colorectal cancer, and lung cancer. However, the development of CDDP resistance largely limits its clinical application. Proteasome inhibitors may enhance traditional chemotherapy agent-induced cytotoxicity and apoptosis. Marizomib (NPI-0052, salinosporamide A, Mzb), a second-generation proteasome inhibitor, shows synergistic anticancer activity with some drugs. Currently, the effect of Mzb on cervical cancer cell proliferation remains unclear. In this study, we explored the role of Mzb in three cervical cancer cell lines, HeLa, CaSki, and C33A, representing major molecular subtypes of cervical cancer and xenografts. We found that Mzb alone showed noteworthy cytotoxic effects, and its combination with CDDP resulted in more obvious cytotoxicity and apoptosis in cervical cancer cell lines and xenografts. In order to investigate the mechanism of this effect, we probed whether Mzb alone or in combination with CDDP had a better antitumor response by enhancing CDDP-induced angiopoietin 1 (Ang-1) expression and inhibiting the expression of TEK receptor tyrosine kinase (Tie-2) in the Ang-1/Tie-2 pathway, FMS-like tyrosine kinase 3 ligand (Flt-3L) and stem cell factor (SCF) as identified by a cytokine antibody chip test. The results suggest that Mzb has better antitumor effects on cervical cancer cells and can sensitize cervical cancer cells to CDDP treatment both in vitro and in vivo. Accordingly, we conclude that the combination of CDDP with Mzb produces synergistic anticancer activity and that Mzb may be a potential effective drug in combination therapy for cervical cancer patients.

Regulation of Magnesium Matrix Composites Materials on Bone Immune Microenvironment and Osteogenic Mechanism.

Despite magnesium based metal materials are widely used in bone defect repair, there are still various deficiencies, and their properties need to be optimized. Composites synthesized with magnesium based metal as matrix are the research hotspot, and the host immune response after biomaterial implantation is very important for bone binding. By studying the immunoregulation of bone biomaterials, it can regulate the immune response in the process of osteogenesis and create a good local immune microenvironment, which is conducive to biomaterials to reduce inflammatory response and promote good bone binding. This article introduces the osteogenic mechanism of magnesium based metal materials and its regulation on bone immune microenvironment in detail.

Borderline ovarian tumor in the pediatric and adolescent population: a clinopathologic analysis of fourteen cases.

Borderline ovarian tumors (BOTs) are rare among children and adolescents. This study was to probe into the clinicopathologic characteristics and prognosis in children and adolescents with BOT. A retrospective investigation was performed on 14 adolescents younger than age 21 years diagnosed with BOT. Clinical presentation, preoperative characteristics, surgery, tumor stage, histology, and recurrence were collected. The results showed that median age at diagnosis was 17.5 years, mostly after menarche. Abdominal mass/pain were the most common presenting symptoms. Median tumor size was 14 cm. Cancer antigen-125 (CA-125) in the blood serum was elevated by 41.67% (5/12), and CA-199 was elevated by 16.67% (2/12). All patients had fertility-preserving surgery: 66.67% (8/12) via laparoscopy (LSC) and cystectomy, 33.33% (4/12) via laparotomy and unilateral salpingo-oophorectomy (USO), and 1 case recurred, and underwent panhysterectomy and bilateral salpingo-oophorectomy. 4 out of 14 tumors (28.57%) had serous and 10 of 14 (71.43%) had mucinous histology. Five tumors showed histological microinvasion. Median follow-up time was 52 months. 10 of 14 cases were alive at last follow-up without disease, and 4 of 14 cases were at lost visit. Thus BOTs in children and adolescents are very rare tumors which have excellent prognosis even in advanced stages, when managed with fertility-preserving procedures. Close follow-up is important because of the high recurrence rates many years after diagnosis.

Microstructure and Impact Toughness of Local-Dry Keyhole Tungsten Inert Gas Welded Joints.

In this paper, the microstructure and impact toughness of a S32101 duplex stainless steel underwater local-dry keyhole tungsten inert gas welded joint were studied. The impact toughness value of the underwater weld metal reached 78% of the onshore weld metal, which is in accordance with the underwater welding standards. The proportion of austenite in the underwater weld metal was 0.9% lower than that of the onshore weld metal. The proportion of the Σ3 coincidence site lattice boundaries and random phase boundaries in the underwater weld metal, which significantly influence the impact toughness of the weld metal, were smaller than that of the onshore weld metal.

Sudden Death as a Sequel of Ruptured Giant Coronary Artery Aneurysm in Kawasaki Disease.

This article reports a case of Kawasaki disease (KD) and its rapid fatal course in a 5-year-old boy, who 3 days before hospitalization demonstrated fever and diffuse erythema in the face, neck, and torso, as well as swelling and pain below the right earlobe. During the admission, he was diagnosed with mumps and suspected scarlet fever. Abnormal laboratory findings included elevated values of procalcitonin, C-reactive protein, and interleukin 6. Sudden death occurred 8 days after admission. Autopsy confirmed the cause of death to be pericardial tamponade due to a ruptured, inflamed aneurysm of the left anterior descending coronary artery. We believe that any typical clinical sign of KD whenever associated with elevated indices of inflammation should set off suspicion of KD and further permit cardiovascular examination. This would contribute to distinguishing KD from other diseases with similar clinical signs in order to accelerate appropriate treatment.

Systematic prediction of target genes and pathways in cervical cancer from microRNA expression data.

Cervical cancer (CC) is a leading cause of cancer-associated mortality in women; thus, the present study aimed to investigated potential target genes and pathways in patients with CC by utilizing an ensemble method and pathway enrichment analysis. The ensemble method integrated a correlation method [Pearson's correlation coefficient (PCC)], a causal inference method (IDA) and a regression method [least absolute shrinkage and selection operator (Lasso)] using the Borda count election algorithm, forming the PCC, IDA and Lasso (PIL) method. Subsequently, the PIL method was validated to be a feasible approach to predict microRNA (miRNA) targets by comparing predicted miRNA targets against those from a confirmed database. Finally, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was conducted for target genes in the 1,000 most frequently predicted miRNA-mRNA interactions to determine target pathways. A total of 10 target genes were obtained that were predicted >5 times, including secreted frizzled-related protein 4, maternally expressed 3 and NIPA like domain containing 4. Additionally, a total of 17 target pathways were identified, of which cytokine-cytokine receptor interaction (P=8.91×10-7) was the most significantly associated with CC of all pathways. In conclusion, the present study predicted target genes and pathways for patients with CC based on miRNA expression data, the PIL method and pathway analysis. The results of the present study may provide an insight into the pathological mechanisms underlying CC, and provide potential biomarkers for the diagnosis and treatment of this tumor type. However, these biomarkers have yet to be validated; these validations will be performed in future studies.

Microstructure Evolution and Mechanical Properties of Underwater Dry and Local Dry Cavity Welded Joints of 690 MPa Grade High Strength Steel.

Q690E high strength low alloy (HSLA) steel plays an important role in offshore structures. In addition, underwater local cavity welding (ULCW) technique was widely used to repair important offshore constructions. However, the high cooling rate of ULCW joints results in bad welding quality compared with underwater dry welding (UDW) joints. Q690E high strength low alloy steels were welded by multi-pass UDW and ULCW techniques, to study the microstructural evolution and mechanical properties of underwater welded joints. The microstructure and fracture morphology of welded joints were observed by scanning electron microscope and optical microscope. The elemental distribution in the microstructure was determined with an Electron Probe Microanalyzer. The results indicated that the microstructure of both two welded joints was similar. However, martensite and martensite-austenite components were significantly different with different underwater welding methods such that the micro-hardness of the HAZ and FZ in the ULCW specimen was higher than that of the corresponding regions in UDW joint. The yield strength and ultimate tensile strength of the ULCW specimen are 109 MPa lower and 77 MPa lower, respectively, than those of the UDW joint. The impact toughness of the UDW joint was superior to those of the ULCW joint.

Next-generation proteasome inhibitor oprozomib enhances sensitivity to doxorubicin in triple-negative breast cancer cells.

Doxorubicin (DOX) is the most common chemotherapeutic drug for treatment of breast cancer but intrinsic and acquired resistance frequently occurs and severe side effects occur at high doses. DOX might induce activation of NF-κB causing this resistance, in which case proteasome inhibitors could inhibit activation of NF-κB by blocking inhibitory factor κB-alpha degradation. Triple-negative breast cancer (TNBC) is highly progressive and there are no established therapeutic targets against TNBC. Although some proteasome inhibitors have been shown to have antitumor effects in breast cancer, the effect of orally bioavailable proteasome inhibitor oprozomib on TNBC proliferation remains unclear. In the present study, we investigated the role of oprozomib in two TNBC lines, MDA-MB-231 and BT-549. Oprozomib had cytotoxic effects on TNBC cells and increased DOX-induced cytotoxic effects and apoptosis by enhancing DOX-induced JNK/p38 MAPK phosphorylation and inhibiting DOX-induced inhibitory factor êB alpha degradation. These results suggest that oprozomib has potent antitumor effects on TNBC in vitro and can sensitize TNBC cells to DOX treatment. The combination of DOX and oprozomib may be an effective and feasible therapeutic option for TNBC.

Microstructure, Pitting Corrosion Resistance and Impact Toughness of Duplex Stainless Steel Underwater Dry Hyperbaric Flux-Cored Arc Welds.

Duplex stainless steel multi-pass welds were made at 0.15 MPa, 0.45 MPa, and 0.75 MPa pressure, simulating underwater dry hyperbaric welding by the flux-cored arc welding (FCAW) method, with welds of normal pressure as a benchmark. The purpose of this work was to estimate the effect of ambient pressure on the microstructure, pitting corrosion resistance and impact toughness of the weld metal. The microstructure measurement revealed that the ferrite content in the weld metal made at 0.45 MPa is the lowest, followed by that of 0.75 MPa and 0.15 MPa. The analysis of potentiodynamic polarization tests at 30 °C and 50 °C demonstrated that the pitting corrosion resistance depends on the phases of the lower pitting resistance equivalent numbers (PREN), secondary austenite and ferrite. The weld metal made at 0.45 MPa had the best resistance to pitting corrosion at 30 °C and 50 °C with the highest PRENs of secondary austenite and ferrite. The weld metal made at 0.15 MPa displayed the lowest pitting corrosion resistance at 30 °C with the lowest PREN of secondary austenite, while the weld metal made at 0.75 MPa was the most seriously eroded after being tested at 50 °C for the lowest PREN of ferrite, with large cluster pits seen in ferrite at 50 °C. The impact tests displayed a typical ductile-brittle transition because of the body-centered cubic (BCC) structure of the ferrite when the test temperature was lowered. All the weld metals met the required value of 34 J at -40 °C according to the ASTM A923. The highest ferrite content corresponded to the worst impact toughness, but the highest toughness value did not correspond to the greatest austenite content. With the decreasing of the test temperature, the drop value of absorbed energy was correlated to the ferrite content. Additionally, in this work, the weld metal made at 0.45 MPa had the best combined properties of pitting resistance and impact toughness.

Novel MDM2 inhibitor SAR405838 (MI-773) induces p53-mediated apoptosis in neuroblastoma.

Neuroblastoma (NB), which accounts for about 15% of cancer-related mortality in children, is the most common childhood extracranial malignant tumor. In NB, somatic mutations of the tumor suppressor, p53, are exceedingly rare. Unlike in adult tumors, the majority of p53 downstream functions are still intact in NB cells with wild-type p53. Thus, restoring p53 function by blocking its interaction with p53 suppressors such as MDM2 is a viable therapeutic strategy for NB treatment. Herein, we show that MDM2 inhibitor SAR405838 is a potent therapeutic drug for NB. SAR405838 caused significantly decreased cell viability of p53 wild-type NB cells and induced p53-mediated apoptosis, as well as augmenting the cytotoxic effects of doxorubicin (Dox). In an in vivo orthotopic NB mouse model, SAR405838 induced apoptosis in NB tumor cells. In summary, our data strongly suggest that MDM2-specific inhibitors like SAR405838 may serve not only as a stand-alone therapy, but also as an effective adjunct to current chemotherapeutic regimens for treating NB with an intact MDM2-p53 axis.

Second-generation proteasome inhibitor carfilzomib enhances doxorubicin-induced cytotoxicity and apoptosis in breast cancer cells.

Proteasome inhibition is an attractive approach for anticancer therapy. Doxorubicin (DOX) is widely used for treatment in a number of cancers including breast cancer; however, the development of DOX resistance largely limits its clinical application. One of the possible mechanisms of DOX-resistance is that DOX might induce the activation of NF-κB. In this case, proteasome inhibitors could inhibit the activation of NF-κB by blocking inhibitory factor κB (IκB) degradation. Carfilzomib, a second-generation proteasome inhibitor, overcomes bortezomib resistance and lessens its side-effects. Currently, the effect of carfilzomib on breast cancer cell proliferation remains unclear. In this study, we exploited the role of carfilzomib in seven breast cancer cell lines, MCF7, T-47D, MDA-MB-361, HCC1954, MDA-MB-468, MDA-MB-231, and BT-549, representing all major molecular subtypes of breast cancer. We found that carfilzomib alone had cytotoxic effects on the breast cancer cells and it increased DOX-induced cytotoxic effects and apoptosis in combination by enhancing DOX-induced JNK phosphorylation and inhibiting DOX-induced IκBα degradation. The results suggest that carfilzomib has potent antitumor effects on breast cancer in vitro and can sensitize breast cancer cells to DOX treatment. DOX in combination with carfilzomib may be an effective and feasible therapeutic option in the clinical trials for treating breast cancer.

Association between micronucleus frequency and cervical intraepithelial neoplasia grade in Thinprep cytological test and its significance.

A micronucleus is an additional small nucleus formed due to chromosomes or chromosomal fragments fail to be incorporated into the nucleus during cell division. In this study, we assessed the utility of micronucleus counting as a screening tool in cervical precancerous lesions in Thinprep cytological test smears under oil immersion. High risk HPV was also detected by hybrid capture-2 in Thinprep cytological test smears. Our results showed that micronucleus counting was significantly higher in high-grade squamous intraepithelial lesion (HSIL) and invasive carcinoma cases compared to low-grade squamous intraepithelial lesion (LSIL) and non-neoplastic cases. Receiver operating characteristic (ROC) curve analysis revealed that micronucleus counting possessed a high degree of sensitivity and specificity for identifying HSIL and invasive carcinoma. Cut-off of 7.5 for MN counting gave a sensitivity of 89.6% and a specificity of 66.7% (P = 0.024 and AUC = 0.892) for detecting HSIL and invasive carcinoma lesions. Multiple linear regression analysis showed that only HSIL and invasive cancer lesions not age, duration of marital life and number of pregnancy are significantly associated with MN counting. The positive rate of high risk HPV was distinctly higher in LSIL, HSIL and invasive cancer than that in non-neoplstic categories. In conclusions, MN evaluation may be viewed as an effective biomarker for cervical cancer screening. The combination of MN count with HPV DNA detection and TCT may serve as an effective means to screen precancerous cervical lesions in most developing nations.

Aquaporin 8 involvement in human cervical cancer SiHa migration via the EGFR-Erk1/2 pathway.

Overexpression of aquaporins (AQPs) has been reported in several human cancers. Epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinases 1/2 (Erk1/2) are associated with tumorigenesis and cancer progression and may upregulate AQP expression. In this study, we demonstrated that EGF (epidermal growth factor) induces SiHa cells migration and AQP8 expression. Wound healing results showed that cell migration was increased by 2.79-1.50-fold at 24 h and 48 h after EGF treatment. AQP8 expression was significantly increased (3.33-fold) at 48 h after EGF treatment in SiHa cells. An EGFR kinase inhibitor, PD153035, blocked EGF-induced AQP8 expression and cell migration and AQP8 expression was decreased from 1.59-fold (EGF-treated) to 0.43-fold (PD153035-treated) in SiHa. Furthermore, the MEK (MAPK (mitogen-activated protein kinase)/Erk (extracellular signal regulated kinase)/Erk inhibitor U0126 also inhibited EGF-induced AQP8 expression and cell migration. AQP8 expression was decreased from 1.21-fold (EGF-treated) to 0.43-fold (U0126-treated). Immunofluorescence microscopy further confirmed the results. Collectively, our findings show that EGF induces AQP8 expression and cell migration in human cervical cancer SiHa cells via the EGFR/Erk1/2 signal transduction pathway.

Expression of aquaporin 8 and phosphorylation of Erk1/2 in cervical epithelial carcinogenesis: correlation with clinicopathological parameters.

Overexpression of aquaporins (AQPs) has been reported in several human cancers. Extracellular signal-regulated kinases 1/2 (Erk1/2) are associated with tumorigenesis and cancer progression and may upregulate AQPs expression. In this study, we examined cervical tissue samples to establish the relationship between Erk1/2 and AQPs in cervical carcinoma by RT-PCR, Western blot and immunohistochemistry. We also examined the relationship between AQP8, Erk1/2 and clinicopathological variables in patients with cervical cancer. Our results showed that Erk1/2 was differentially expressed at the level of transcription and was most highly expressed in CIN samples (P < 0.05). At the level of translation, significant differences were seen in the expression of AQP8, Erk1/2 and P-Erk1/2 (P < 0.05). Expression was highest in CIN samples, where 80.9%, 76.6%, and 66% of samples were positive for AQP8, Erk1/2 and P-Erk1/2, respectively. Expression in cervical carcinoma samples was higher than in normal cervical tissues (P < 0.01). AQP8 expression was associated with the depth of invasion of cervical cancer cells, and the expression of Erk1/2 and P-Erk1/2 was increased in earlier clinical stages and in lymphatic metastasis. AQP8 expression was positively correlated with Erk1/2 expression in cervical cancer. In conclusions, increased AQP8, Erk1/2 and P-Erk1/2 expression may play a role in transformation of CIN into cervical cancer, and in early invasion and lymphatic metastasis of cervical cancer. These proteins could potentially be used as molecular markers for early diagnosis of cervical carcinoma.

Expression and prognostic value of aquaporin 1, 3 in cervical carcinoma in women of Uygur ethnicity from Xinjiang, China.

BACKGROUND: Overexpression of several aquaporins has been reported in different types of human cancer but the role of aquaporins in carcinogenesis has not yet been clearly defined. There is few report concerning role of aquaporins in human cervical carcinogenesis so far. Here, we determined the expression and prognostic value of aquaporin 1, 3 in cervical carcinoma in Chinese women of Uygur ethnicity. METHODS AND RESULTS: Real-time PCR analyses demonstrated aquaporin 1, 3 mRNA were differentially expressed in cervical carcinoma, CIN 2-3 and mild cervicitis. Immunofluorescent and immunohistochemical analyses demonstrated aquaporin 1 was predominantly localized to stromal endothelial cells in cervical lesions. Aquaporin 3 was localized to the membrane of normal squamous epithelium, CIN and carcinoma cells. Aquaporin 1 and 3 were upregulated in cervical cancer compared to mild cervicitis and CIN2-3 (P<0.05); Tumor expression of aquaporin 1, 3 significantly increased in advanced stage disease, and patients with deeper tumor infiltration, lymph node metastases or larger tumor volume (P<0.05). Multivariate analysis demonstrated that aquaporin 1, 3 were not independent prognostic factors in cervical carcinoma. CONCLUSION: Aquaporins may participate in the initiation and progression of cervical carcinoma by promoting tumor growth, invasion or lymph node metastasis. Further study is required to determine whether aquaporins have potential as prognostic factors in cervical cancer.

Aquaporin-8 mediates human esophageal cancer Eca-109 cell migration via the EGFR-Erk1/2 pathway.

Abnormal expression of aquaporins (AQPs) has been reported in several human cancers. Epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinases1/2 (ERK1/2) are associated with tumorigenesis and cancer progression and may upregulate AQPs expression. In this study, we investigated acquaporin-8 expression and signaling via epidermal growth factor receptor-extracellular signal-regulated kinases1/2 in human esophageal cancer Eca-109 cells by western blot, immunofluorescence and wound healing (scratch) assays. Our results showed that epidermal growth factor (EGF) induced both Eca-109 migration and AQP8 expression. Wound healing results showed that cell migration was increased by 1.23-1.10-fold at 24 h and 48 h after EGF treatment. AQP8 expression was significantly increased (1.19-fold) at 48 h after EGF treatment in Eca-109. The EGFR kinase inhibitor, PD153035, blocked EGF-induced AQP8 expression and cell migration. AQP8 expression was decreased from 3.65-fold (EGF-treated) to 0.55-fold (PD153035-treated) in Eca-109. Furthermore, the MEK [MAPK (mitogen-activated protein kinase)/Erk1/2]/Erk1/2 inhibitor U0126 also inhibited EGF-induced AQP8 expression and cell migration. AQP8 expression was decreased from 3.92-fold (EGF-treated) to 1.38-fold (U0126-treated) in Eca-109. In conclusions, EGF induces AQP8 expression and cell migration in Eca-109 cells via the EGFR/Erk1/2 signal transduction pathway.

[Expression of monocyte chemotactic protein-1 and its receptor in sudden coronary death].

OBJECTIVE: To investigate the expression of monocyte chemotactic protein-1 (MCP-1) and its receptor CC chemokine receptor-2 (CCR-2) in coronary atherosclerosis plaques between sidden coronary death (SCD) and non-SCD. Methods The expression levels of MCP-1 and CCR-2 in SCD group, coronary atherosclerosis group (non-SCD), control group (normal coronary artery) were detected by immunohistochemistry. RESULTS: Positive rates of MCP-1 among the three groups were 78%, 47%, and 0%, respectively, with significant expressing differences between each two groups (P<0.05). Positive rates of CCR-2 among three groups were 72%, 47%, and 0%, respectively, with significant expressing differences between the SCD group and coronary atherosclerosis group as well as between the SCD group and control group (P<0.05), but with no significant expressing difference between coronary atherosclerosis group and control group (P>0.05). CONCLUSION: Overexpression of MCP-1 and CCR-2 in coronary atherosclerotic plaques is closely correlated with SCD.