Fibulin7 Mediated Pathological Cardiac Remodeling through EGFR Binding and EGFR-Dependent FAK/AKT Signaling Activation.

Adverse remodeling after myocardial infarction (MI) result in heart failure and sudden cardiac death. Fibulin7 (FBLN7) is an adhesion protein excreted into the extracellular matrix that functions in multiple biological processes. However, whether and how FBLN7 affects post-MI cardiac remodeling remains unclear. Here, the authors identify FBLN7 as a critical profibrotic regulator of adverse cardiac remodeling. They observe significantly upregulated serum FBLN7 levels in MI patients with left ventricular remodeling compared to those without MI. Microarray dataset analysis reveal FBLN7 is upregulated in human heart samples from patients with dilated and hypertrophic cardiomyopathy compared with non-failing hearts. The authors demonstrate that FBLN7 deletion attenuated post-MI cardiac remodeling, leading to better cardiac function and reduced myocardial fibrosis, whereas overexpression of FBLN7 results in the opposite effects. Mechanistically, FBLN7 binds to the epidermal growth factor receptor (EGFR) through its EGF-like domain, together with the EGF-like calcium-binding domain, and induces EGFR autophosphorylation at tyrosine (Y) 1068 and Y1173, which activates downstream focal adhesion kinase/AKT signaling, thereby leading to fibroblast-to-myofibroblast transdifferentiation. In addition, FBLN7-EGFR mediates this signal transduction, and the fibrotic response is effectively suppressed by the inhibition of EGFR activity. Taken together, FBLN7 plays an important role in cardiac remodeling and fibrosis after MI.

Heat shock protein: a double-edged sword linking innate immunity and hepatitis B virus infection.

Heat shock proteins (HSPs), which have a variety of functions, are one of the stress protein families. In recent years, They have been reported to play a dual role in hepatitis B virus (HBV) which as persistent infection which is associated with, cirrhosis and liver cancer. In this article, we have summarized the regulatory mechanisms between HSPs and viruses, especially HBV and associated diseases based on HSP biological functions of in response to viral infections. In view of their potential as broad-spectrum antiviral targets, we have also discuss current progress and challenges in drug development based on HSPs, as well as the potential applications of agents that have been evaluated clinically in HBV treatment.

Aptamer functionalized cell membrane for brain and nerve cell sensing with high sensitivity and stability.

Accurate dopamine (DA) monitoring with high stability is essential for investigating the chemical basis of brain function and pathology. Electrochemical-based tissue-implantable carbon fiber electrodes (CFEs) show great potential in sensing the dynamics of neurochemicals at a sub-second timescale. However, their anti-fouling property, selectivity, and stability pose challenges. Here, we presented a novel strategy to enhance electrode biocompatibility and stability by modifying CFE with a chitosan (CS) film, brain cell membrane (M), and aptamer cholesterol amphiphiles (DNA-cho). We found that CFE was uniformly covered by a cicada-like membrane after being modified. Electrochemical characterizations indicated that DNA-cho-M-CS-CFE exhibited a wide linear range of DA concentration and showed high sensitivity, specificity, and stability. The electrode also presented excellent fouling resistance and biocompatibility. Moreover, the biosensor was used to detect DA in K+-induced brain slices and PC12 cells with a satisfactory stability and sensitivity and to prove that LPS treatment leads to the delayed and decreased release of DA. DNA-cho-M-CS-CFE showed excellent electrochemical performance and unique advantages for long-term in vivo sensing of living cells, thus providing a new feasible scheme for studying neurochemical kinetics and brain diseases.

Oscillatory shear stress promotes vein graft intimal hyperplasia via NADPH oxidase-related pathways.

Background: Uncontrolled intimal hyperplasia (IH) after autologous saphenous vein grafting triggers a high restenosis rate; however, its association with the activation of NADPH oxidase (NOX)-related pathways is unclear. Here, we investigated the effects and mechanism of oscillatory shear stress (OSS) on grafted vein IH. Methods: Thirty male New Zealand rabbits were randomly divided into control, high-OSS (HOSS), and low-OSS (LOSS) groups, and the vein grafts were harvested after 4 weeks. Hematoxylin and eosin staining and Masson staining assays were used to observe morphological and structural changes. Immunohistochemical staining was used to detect α-SMA, PCNA, MMP-2, and MMP-9 expression. Immunofluorescence staining was used to observe reactive oxygen species (ROS) production in the tissues. Western blotting was used to determine the expression levels of pathway-related proteins (NOX1, NOX2, AKT, p-AKT, and BIRC5), PCNA, BCL-2, BAX, and caspase-3/cleaved caspase-3 in tissues. Results: Blood flow velocity was lower in the LOSS group than in the HOSS group, while vessel diameter did not change significantly. Shear rate was elevated in both HOSS and LOSS groups but was higher in the HOSS group. Additionally, vessel diameter increased with time in the HOSS and LOSS groups, whereas flow velocity did not. Intimal hyperplasia was significantly lower in the LOSS group than in the HOSS group. IH was dominated by smooth muscle fibers in the grafted veins and collagen fibers in the media. OSS restriction significantly reduced the α-SMA, PCNA, MMP-2, and MMP-9 levels. Moreover, ROS production and the expression of NOX1, NOX2, p-AKT, BIRC5, PCNA, BCL-2, BAX, and cleaved caspase-3 were phase-reduced in LOSS compared to the levels in the HOSS group. Total AKT was not differentially expressed among the three groups. Conclusion: OSS promotes the proliferation, migration, and survival of subendothelial vascular smooth muscle cells in grafted veins, which may be related to the regulation of downstream p-AKT/BIRC5 levels through the increased production of ROS by NOX. Drugs inhibiting this pathway might be used to prolong vein graft survival time.

The Level and Significance of Circulating Angiotensin-III in Patients with Coronary Atherosclerosis.

OBJECTIVE: Angiotensin-III (Ang-III) is the downstream product of angiotensin-II (Ang-II) metabolized by aminopeptidase A (APA). At present, the research of Ang-III mainly concentrates on hypertension and the central renin-angiotensin system (RAS). However, few studies have focused on the relationship between Ang-III and coronary atherosclerosis (CAS). METHODS AND RESULTS: Plasma Ang-III and APA levels were measured by the enzyme-linked immunosorbent assay (ELISA) in 44 normal subjects and 84 patients confirmed as having CAS by coronary angiography. Circulating Ang-III levels were significantly lower in patients with CAS than in normal controls (P = 0.013). APA levels were slightly lower in the CAS group (P = 0.324). According to the severity of atherosclerosis, CAS patients were divided into two groups. Compared with the controls, the APA and Ang-III levels were lower in the high scoring group and APA decreased significantly. CONCLUSIONS: Circulating Ang-III levels were reduced in patients with CAS, and the possible reason may be related to the decrease in the APA level.

MicroRNA-211 suppresses prostate cancer proliferation by targeting SPARC.

Dysregulation of microRNAs (miRNAs/miRs) is frequently associated with cancer progression. Altered expression of miR-211 has been observed in various types of human cancer; however, its expression and role in prostate cancer (PCa) remains unknown. In the present study, the expression of miR-211 in PCa cell lines and tissues was measured by reverse transcription-quantitative PCR (qPCR), revealing that miR-211 was downregulated in PCa cell lines and tissues. Further analysis revealed that low miR-211 was associated with the tumor stage and Gleason score. With the assistance of miR-211 mimics and inhibitor, it was also revealed that the overexpression of miR-211 could inhibit PCa cell proliferation in vitro. Conversely, downregulated miR-211 expression promotes PCa cell proliferation. In addition, the secreted protein acidic and rich in cysteine (SPARC) was identified as a target of miR-211 in the PCa cell lines, and SPARC expression was inversely associated with miR-211. In conclusion, it was demonstrated that the miR-211 expression was downregulated in PCa cell lines and tissues. Additionally, miR-211 could inhibit PCa cell proliferation partially by downregulating SPARC. Therefore, miR-211 may be a potential therapeutic target for PCa treatment in the future.

[Practices and Discusses on Medical Equipment Information Management of Military Hospital].

This paper briefly expounds the present situation of medical equipment information management in military hospitals. From basic structure and main function of the software systems, it gives a detailed introduction of the probes and researches on medical equipment information management in recent years. It analyzes the existing problems and shortcomings, combined with the previous achievements and effects, and then it introduces the ideas and goals of the new medical equipment management information system, which now being developed. Then it discusses the key problems of the new system which need to be solved.

Intravenous flurbiprofen axetil enhances analgesic effect of opioids in patients with refractory cancer pain by increasing plasma ß-endorphin.

BACKGROUND: The study aimed to investigate the analgesic effect of a combination of intravenous flurbiprofen axetil and opioids, and evaluate the relationship between refractory pain relief and plasma ß-endorphin levels in cancer patients. MATERIALS AND METHODS: A total of 120 cancer patients was randomly divided into two groups, 60 patients took orally morphine sulfate sustained-release tablets in group A, and another 60 patients receiving the combination treatment of intravenous flurbiprofen axetil and opioid drugs in group B. After 7 days, pain relief, quality of life improvement and side effects were evaluated. Furthermore, plasma ß-endorphin levels were measured by radioimmunoassay. RESULTS: With the combination treatment of intravenous intravenous flurbiprofen axetil and opioids, the total effective rate of pain relief rose to 91.4%, as compared to 82.1% when morphine sulfate sustained-release tablet was used alone. Compared with that of group A, the analgesic effect increased in group B (p=0.031). Moreover, satisfactory pain relief was associated with a significant increase in plasma ß-endorphin levels. After the treatment, plasma ß-endorphin level in group B was 62.4±13.5 pg/ml, which was higher than that in group A (45.8±11.2 pg/ml) (p<0.05). CONCLUSIONS: Our results suggest the combination of intravenous flurbiprofen axetil and opioids can enhance the analgesic effect of opioid drugs by increasing plasma ß-endorphin levels, which would offer a selected and reliable strategy for refractory cancer pain treatment.

Retrieval of absorption and backscattering coefficients from HJ-1A/CCD imagery in coastal waters.

A simple semi-analytical model (SAB) was developed for computing a(560) and b(b)(550) from HJ-1A/CCD images. By comparison with field measurements, the SAB model produces 5.3-23.5% uncertainty for a(560) and b(b)(550) retrievals. The a(560) and b(b)(550) are also retrieved from satellite images. The match-up analysis results indicate that a(560) and b(b)(550) may be derived from the HJ-1A/CCD images with respective uncertainties of 29.84 and 21.35%. These findings imply that, provided that an atmospheric correction scheme for the green bands is available, the extensive database of HJ-1A/CCD imagery may be used for the quantitative monitoring of optical properties in coastal waters.

M2-polarized macrophages promote metastatic behavior of Lewis lung carcinoma cells by inducing vascular endothelial growth factor-C expression.

OBJECTIVES: Tumor-associated macrophages that generally exhibit an alternatively activated (M2) phenotype have been linked to tumor progression and metastasis. However, the role of M2-polarized macrophages in the growth and metastasis of lung adenocarcinoma remains enigmatic. The aim of this study was to explore the effect of M2 macrophages on the proliferation and migration of mouse Lewis lung carcinoma cells and tumor-induced lymphangiogenesis. METHODS: Trypan blue staining and the Transwell migration assay were performed to evaluate the effects of activated (M1 or M2) macrophages on the proliferation and migration of Lewis cells. Furthermore, vascular endothelial growth factor-C expression in Lewis cells and nitric oxide secretion from activated macrophages were detected during the co-culture assay. Following treatment with activated macrophages, lymphatic endothelial cells differentiated into capillary-like structures, and the induction of Lewis cell migration was assessed using a two-dimensional Matrigel-based assay. RESULTS: In the co-culture Transwell system, the proliferation and migration of Lewis cells were promoted by M2 macrophages. Moreover, the co-culture significantly increased the expression of vascular endothelial growth factor-C by Lewis cells and reduced the secretion of nitric oxide from M2 macrophages, which subsequently led to the capillary morphogenesis of lymphatic endothelial cells. Interestingly, following co-culture with Lewis cells, the function of RAW264.7 cells was polarized toward that of the M2 macrophage phenotype. CONCLUSION: M2-polarized macrophages promoted the metastatic behavior of Lewis cells by inducing vascular endothelial growth factor-C expression. Thus, the interruption of signaling between M2 macrophages and Lewis cells may be considered to be a new therapeutic strategy.

Peritumoral lymphatic microvessel density is related to poor prognosis in lung adenocarcinoma: A retrospective study of 65 cases.

Although recent investigations have identified that lymphangiogenesis is associated with regional lymph node metastasis and tumor prognosis in non-small cell lung cancer (NSCLC), peritumoral lymphatic microvessel density (LMVD) and its prognostic significance in lung adenocarcinoma remain unknown. In the present study, we assessed peritumoral LMVD in lung adenocarcinoma and investigated its correlation with patient prognosis. Using immunohistochemistry (SP method), the D2-40-positive peritumoral LMVD count in lung adenocarcinoma was found to be 11.56±10.73, which was higher than intratumoral LMVD (P<0.001), and was found to be associated with lymphatic metastasis (P=0.003) and pTNM staging (P=0.046). Furthermore, a significant difference in the patient overall survival time was demonstrated between tumors with a high peritumoral LMVD and those with a low peritumoral LMVD (P=0.005). Finally, using multivariate analysis, it was determined that peritumoral LMVD, lymphatic metastasis and pTNM staging were independent prognostic factors. In conclusion, the results suggest that D2-40-positive peritumoral LMVD may predict the prognosis of lung adenocarcinoma.

M2-polarized macrophages promote metastatic behavior of Lewis lung carcinoma cells by inducing vascular endothelial growth factor-C expression

OBJECTIVES: Tumor-associated macrophages that generally exhibit an alternatively activated (M2) phenotype have been linked to tumor progression and metastasis. However, the role of M2-polarized macrophages in the growth and metastasis of lung adenocarcinoma remains enigmatic. The aim of this study was to explore the effect of M2 macrophages on the proliferation and migration of mouse Lewis lung carcinoma cells and tumor-induced lymphangiogenesis. METHODS: Trypan blue staining and the Transwell migration assay were performed to evaluate the effects of activated (M1 or M2) macrophages on the proliferation and migration of Lewis cells. Furthermore, vascular endothelial growth factor-C expression in Lewis cells and nitric oxide secretion from activated macrophages were detected during the co-culture assay. Following treatment with activated macrophages, lymphatic endothelial cells differentiated into capillary-like structures, and the induction of Lewis cell migration was assessed using a twodimensional Matrigel-based assay. RESULTS: In the co-culture Transwell system, the proliferation and migration of Lewis cells were promoted by M2 macrophages. Moreover, the co-culture significantly increased the expression of vascular endothelial growth factor-C by Lewis cells and reduced the secretion of nitric oxide from M2 macrophages, which subsequently led to the capillary morphogenesis of lymphatic endothelial cells. Interestingly, following co-culture with Lewis cells, the function of RAW264.7 cells was polarized toward that of the M2 macrophage phenotype. CONCLUSION: M2-polarized macrophages promoted the metastatic behavior of Lewis cells by inducing vascular endothelial growth factor-C expression. Thus, the interruption of signaling between M2 macrophages and Lewis cells may be considered to be a new therapeutic strategy.

M2-polarized tumor-associated macrophages are associated with poor prognoses resulting from accelerated lymphangiogenesis in lung adenocarcinoma.

OBJECTIVES: Tumor-associated macrophages have been implicated in promoting tumor growth, progression and metastasis. However, the activated phenotype (M1 or M2) of tumor-associated macrophages remains unknown in solid tumors. Therefore, this study examined the density and prognostic significance of M2-polarized tumor-associated macrophages in lung adenocarcinoma. METHODS: Tumor specimens from 65 lung adenocarcinoma patients were assessed by ELISA for Th1/Th2 cytokine concentrations. The activated phenotype (M1 or M2) of tumor-associated macrophages was determined utilizing immunofluorescence staining. Additionally, to evaluate lymphangiogenesis, peritumoral lymphatic microvessel density was measured using D2-40. The correlation between tumor-associated macrophage subtype and overall patient survival was analyzed using the Kaplan-Meier method and compared using the log-rank test. RESULTS: A shift toward Th2 cytokine expression was detected within lung adenocarcinoma microenvironments. Approximately 79.71±16.27% of tumor-associated macrophages were M2 polarized; the remaining 20.35±5.31% were M1 polarized. The infiltration of M2-polarized macrophages was significantly associated with P-TNM staging and lymph node metastasis. The peritumoral lymphatic microvessel density was significantly higher in the high M2-polarized tumor-associated macrophage group than in the low M2-polarized tumor-associated macrophage group. A significant difference in overall patient survival was detected not only between patients with tumors with high and low macrophage counts but also between patients with tumors with high and low counts of M2-polarized macrophages. CONCLUSION: Tumor-associated macrophages in lung adenocarcinoma have an M2-polarized subtype and are associated with poor prognoses, perhaps resulting from accelerated lymphangiogenesis and lymph node metastasis.

M2-Polarized tumor-associated macrophages are associated with poor prognoses resulting from accelerated lymphangiogenesis in lung adenocarcinoma

OBJECTIVES: Tumor-associated macrophages have been implicated in promoting tumor growth, progression and metastasis. However, the activated phenotype (M1 or M2) of tumor-associated macrophages remains unknown in solid tumors. Therefore, this study examined the density and prognostic significance of M2-polarized tumor-associated macrophages in lung adenocarcinoma. METHODS: Tumor specimens from 65 lung adenocarcinoma patients were assessed by ELISA for Th1/Th2 cytokine concentrations. The activated phenotype (M1 or M2) of tumor-associated macrophages was determined utilizing immunofluorescence staining. Additionally, to evaluate lymphangiogenesis, peritumoral lymphatic microvessel density was measured using D2-40. The correlation between tumor-associated macrophage subtype and overall patient survival was analyzed using the Kaplan-Meier method and compared using the log-rank test. RESULTS: A shift toward Th2 cytokine expression was detected within lung adenocarcinoma microenvironments. Approximately 79.71±16.27 percent of tumor-associated macrophages were M2 polarized; the remaining 20.35±5.31 percent were M1 polarized. The infiltration of M2-polarized macrophages was significantly associated with P-TNM staging and lymph node metastasis. The peritumoral lymphatic microvessel density was significantly higher in the high M2-polarized tumor-associated macrophage group than in the low M2-polarized tumor-associated macrophage group. A significant difference in overall patient survival was detected not only between patients with tumors with high and low macrophage counts but also between patients with tumors with high and low counts of M2-polarized macrophages. CONCLUSION: Tumor-associated macrophages in lung adenocarcinoma have an M2-polarized subtype and are associated with poor prognoses, perhaps resulting from accelerated lymphangiogenesis and lymph node metastasis.

[Studies on blood viscosity and external thrombus in patients with silicosis and silicosis complicated with tuberculosis].

OBJECTIVE: To explore the changes of blood viscosity and external thrombus in patients with silicosis and silicosis complicated with tuberculosis (TB). METHOD: Blood viscosity and external thrombus were measured in 288 patients with silicosis, 178 patients with silicosis complicated by TB and 150 healthy subjects. RESULTS: Blood viscosity and external thrombus value were significantly higher in the patients of silicosis and silicosis complicated with TB than in the healthy controls, except for patients of phase I of silicosis. Blood viscosity in the silicotics increased significantly with the advance of the disease, but no significant difference in external thrombus between patients in different phases. Apparent viscosity of whole blood significantly increased in the high-shear rate (200 s(-1)) and middle-shear rate (30 s(-1)) in patients of silicosis complicated with TB than in those without complication of TB at the same phases, but not seen in the low-shear rate (5 s(-1)) and in plasma viscosity, and the length and dried weight of external thrombus increased significantly too. There was no significant difference in blood viscosity and external thrombus between patients of silicosis at phase III and those of silicosis complicated with TB at the same phase. CONCLUSION: Blood in patients with silicosis appeared highly viscous and highly coagulant status. Blood viscosity and external thrombus value significantly increased with the advance of the disease, especially in the patients complicated with TB.