Continuous Infusion of Angiotensin IV Protects against Acute Myocardial Infarction via the Inhibition of Inflammation and Autophagy.

Acute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide. Angiotensin (Ang) IV possesses many biological properties that are not yet completely understood. Therefore, we investigated the function and mechanism of Ang IV in AMI in in vivo and in vitro conditions. AMI was performed by ligation of the left anterior descending coronary artery (LAD) in male C57 mice. Ang IV was continuously infused by a minipump 3 d before AMI for 33 d. The neonatal rat ventricular myocytes (NRVCs) were stimulated with Ang IV and cultured under hypoxic conditions. In vivo, Ang IV infusion significantly reduced the mortality after AMI. By the 7th day after AMI, compared with the AMI group, Ang IV reduced the inflammatory cytokine expression. Moreover, terminal deoxyribonucleotidyl transferase- (TDT-) mediated dUTP nick-end labeling (TUNEL) assay showed that Ang IV infusion reduced AMI-induced cardiomyocyte apoptosis. Compared with AMI, Ang IV reduced autophagosomes in cardiomyocytes and improved mitochondrial swelling and disarrangement, as assessed by transmission electron microscopy. By 30th day after AMI, Ang IV significantly reduced the ratio of heart weight to body weight. Echocardiography showed that Ang IV improved impaired cardiac function. Hematoxylin and eosin (H&E) and Masson staining showed that Ang IV infusion reduced the infarction size and myocardial fibrosis. In vitro, dihydroethidium (DHE) staining and comet assay showed that, compared with the hypoxia group, Ang IV reduced oxidative stress and DNA damage. Enzyme-linked immunosorbent assay (ELISA) showed that Ang IV reduced hypoxia-induced secretion of the tumor necrosis factor- (TNF-) ɑ and interleukin- (IL-) 1ß. In addition, compared with the hypoxia group, Ang IV reduced the transformation of light chain 3- (LC3-) I to LC3-II but increased p62 expression and decreased cardiomyocyte apoptosis. Overall, the present study showed that Ang IV reduced the inflammatory response, autophagy, and fibrosis after AMI, leading to reduced infarction size and improved cardiac function. Therefore, administration of Ang IV may be a feasible strategy for the treatment of AMI.

Prediction of Long Non-Coding RNAs Based on Deep Learning.

With the rapid development of high-throughput sequencing technology, a large number of transcript sequences have been discovered, and how to identify long non-coding RNAs (lncRNAs) from transcripts is a challenging task. The identification and inclusion of lncRNAs not only can more clearly help us to understand life activities themselves, but can also help humans further explore and study the disease at the molecular level. At present, the detection of lncRNAs mainly includes two forms of calculation and experiment. Due to the limitations of bio sequencing technology and ineluctable errors in sequencing processes, the detection effect of these methods is  not very satisfactory. In this paper, we constructed a deep-learning model to effectively distinguish lncRNAs from mRNAs. We used k-mer embedding vectors obtained through training the GloVe algorithm as input features and set up the deep learning framework to include a bidirectional long short-term memory model (BLSTM) layer and a convolutional neural network (CNN) layer with three additional hidden layers. By testing our model, we have found that it obtained the best values of 97.9%, 96.4% and 99.0% in F1score, accuracy and auROC, respectively, which showed better classification performance than the traditional PLEK, CNCI and CPC methods for identifying lncRNAs. We hope that our model will provide effective help in distinguishing mature mRNAs from lncRNAs, and become a potential tool to help humans understand and detect the diseases associated with lncRNAs.

Urinary tract lymphoma: a clinical analysis of 16 cases and review of literature / 白血病·淋巴瘤

Objective To analyze the clinical features, treatment outcomes and prognosis of patients with urinary tract lymphoma. Methods The clinical data of 16 patients in Tongji Hospital of Tongji University from January 2009 to April 2016 were collected and retrospectively analyzed. Results The median age of these patients was 68 years. The onset symptoms of 14 cases were related to urinary system and imaging studies of 10 cases showed masses in the urinary system. The onset regions of lymphoma included:4 cases were renal lymphoma, 5 cases were adrenal lymphoma, 5 cases were testicular lymphoma, 1 case was prostate lymphoma and 1 case was from urethral mouth. The histological type of 12 cases was diffuse large B-cell lymphoma and 10 patients were non-germinal center B cell-like (non-GCB) molecular profiling. Twelve cases belonged to Ann Arbor stages ⅢE- ⅣE, 10 cases had international prognostic index scores ≥3, and 7 cases had B symptoms. 10 patients were confirmed by surgery. Fourteen cases accepted rituximab-containing regimen chemotherapy. Five cases achieved complete response and 3 were partial response. Conclusions The clinical manifestations and imagine examination of patients with urinary tract lymphoma are lack of specificity. The clinical features are highly aggressive and most of the patients are diagnosed at advanced stage. The main histological type is diffuse large B-cell lymphoma and non-GCB molecular profiling. Treatment regimens include surgery combined with chemotherapy and radiotherapy. Earlier diagnosis and treatment may improve the survival of patients.

Lipocalin 2 regulates intestine bacterial survival by interplaying with siderophore in a weaned piglet model of Escherichia coli infection.

Iron is an essential nutrient that facilitates cell proliferation and growth, which plays a pivotal role in modulating the battle for survival between mammalian hosts and their pathogens. Pathogenic bacteria secrete siderophores to acquire iron from the host. However, lipocalin 2 (Lcn2), a siderophore-binding antimicrobial protein, binds to siderophores to prevent bacterial uptake of iron, which is critical for the control of systemic infection with Escherichia coli (E. coli). But few studies focus on the anti-infective response of Lcn2 in the intestines by inhibiting bacterial proliferation based on microbial iron metabolism. In this study, we showed that iron was sequestrated within cells in a piglet model of E. coli K88 infection. Siderophores was produced following E. coli K88 infection and siderophore-related genes expression was upregulated in iron-deficiency environment in vitro. Meanwhile, we found that Lcn2 expression was rapidly and robustly induced in jejunum by E. coli K88 infection and could be stimulated by IL-17 and IL-22. Furthermore, both Lcn2 induced in epithelial cells IPEC-1 and added exogenously as a recombinant protein could inhibit the growth of E. coli. We can conclude that Lcn2 is a crucial component of mucosal immune defense against intestinal infection with E. coli K88.

[Levels of IL-8,IL-10 in patients with chronic periodontitis and coronary heart disease].

PURPOSE: To detect the level of interleukin-8 (IL-8) and interleukin-10 (IL-10) in serum and gingival crevicular fluid in patients with chronic severe periodontitis (CP) and coronary heart disease (CHD) and investigate the relationship between CP and CHD. METHODS: Thirty patients with CHD and CP(group A), twenty-five patients with only CP(group B) and thirty healthy controls (group C) were included in this study. Gingival crevicular fluid and serum IL-8, IL-10 levels were detected by ELISA. SPSS 11.5 software package was used for statistical analysis. RESULTS: The periodontal indexes including bleeding on probing and probing depth were significantly different among the 3 groups. In group A and B, the level of IL-8 in gingival crevicular fluid and serum were significantly lower, whereas the IL-10 level was significantly higher, in comparison to those in group C (P<0.05). CONCLUSIONS: IL-8 and IL-10 may be associated with the pathogenesis of periodontitis and CHD. There may be a relationship between CHD and CP.

Treatment of Ph-adult acute lymphoblastic leukemia patients with Tongji-96 regimen / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and side effects of the consecutive chemotherapeutic protocol, Tongji-96, for adult patients with Philadelphia chromosome negative acute lymphoblastic leukemia (Ph-aALL).</p><p><b>METHODS</b>A retrospective analysis was conducted on 95 cases of Ph-aALL patients treated between January 2004 and December 2012 with Tongji-96 regimen in Tongji hospital, Shanghai.</p><p><b>RESULTS</b>Among these 95 patients, the overall complete remission (CR) rate was 92.6%, 7-year overall survival (OS) and event-free survival (EFS) rates were (39.3±5.9)% and (31.5±5.3)%, respectively, with the median survival of 28 months. Based on multivariable COX proportional hazards regression model analysis, patients with the poor karyotype and failed to achieve CR after first course induction therapy had a higher risk of mortality compared to those who had good or normal cytogenetics and achieved CR after 1 course of induction treatment [the risk ratios (RR) were 3.380 (95% CI 1.530-7.463, P=0.003) and 3.005 (95% CI 1.522-5.933, P=0.002)，respectively]. By means of Kaplan-Meier analysis and Log-rank test，patients aged less than 60 years and successively achieved CR after first induction therapy had more favorable 7-year OS and EFS rates. Patients with normal karyotype and hyperdiploidy had significantly higher 2-year OS and EFS rates compared with those with complex karyotype, t(4;11) translocation and other karyotypes.</p><p><b>CONCLUSION</b>Age (60 years as the cut-off)，treatment courses for achieving CR and cytogenetics were predictive factors for the prognosis of Ph-aALL from this retrospective study. As a comprehensive and sequential therapy protocol, Tongji-96 regimen was proved to obtain long-term survival, reduce risks for relapse and improve outcomes for part Ph-aALL patients.</p>

[Study on predicting total acid content and soluble sugar of tomato juice by near infrared optical fiber spectrometer technique].

In order to explore a simple, rapid and efficient tomato quality detection method, in the present experiment near infrared spectroscopy and optical fiber sensing technology were applied to quickly measure the nutrition ingredient content in tomato juice samples. The main instrument used in this experiment was near infrared optical fiber spectrometer in a wavelength range from 900 to 2 500 nm, which measured the absorbance of the tomato juice samples; A collection of one hundred and sixty-four tomato juice samples were selected as the standard samples, the spectra and the corresponding chemical value were measured. Partial least squares (PLS) was adopted to establish the mathematical model of the total acid and soluble sugar content in tomato juice samples, and the regression equation was statistically analysed. The total acid in tomato juice prediction correlation coefficient was 0.967, calibration standard deviation (RMSEC) was 0.133, standard error of prediction (RMSEP) was 0.103; the soluble sugar prediction correlation coefficient is 0.976, calibration standard deviation (RMSEC) was 0.463, and the standard error of prediction (RMSEP) was 0. 460. The above data achieved better forecasting results, which showed that the method of quantitative analysis of tomato fruit multicomponent content was feasible. The method is rapid, simple and can do multicomponent analysis on the same sample simultaneously. It is a promising sensor and gradually becoming a international research focus in sensor field.

Non-coding RNAs and gastric cancer.

Non-coding RNAs (ncRNAs) play key roles in development, proliferation, differentiation and apoptosis. Altered ncRNA expression is associated with gastric cancer occurrence, invasion, and metastasis. Moreover, aberrant expression of microRNAs (miRNAs) is significantly related to gastric cancer tumor stage, size, differentiation and metastasis. MiRNAs interrupt cellular signaling pathways, inhibit the activity of tumor suppressor genes, and affect the cell cycle in gastric cancer cells. Some miRNAs, including miR-21, miR-106a and miR-421, could be potential markers for the diagnosis of gastric cancer. Long non-coding RNAs (lncRNAs), a new research hotspot among cancer-associated ncRNAs, play important roles in epigenetic, transcriptional and post-transcriptional regulation. Several gastric cancer-associated lncRNAs, such as CCAT1, GACAT1, H19, and SUMO1P3, have been explored. In addition, Piwi-interacting RNAs, another type of small ncRNA that is recognized by gastroenterologists, are involved in gastric carcinogenesis, and piR-651/823 represents an efficient diagnostic biomarker of gastric cancer that can be detected in the blood and gastric juice. Small interfering RNAs also function in post-transcriptional regulation in gastric cancer and might be useful in gastric cancer treatment.

[Rapid discriminating hogwash oil and edible vegetable oil using near infrared optical fiber spectrometer technique].

In the present study, a new method using near infrared spectroscopy combined with optical fiber sensing technology was applied to the analysis of hogwash oil in blended oil. The 50 samples were a blend of frying oil and "nine three" soybean oil according to a certain volume ratio. The near infrared transmission spectroscopies were collected and the quantitative analysis model of frying oil was established by partial least squares (PLS) and BP artificial neural network The coefficients of determina- tion of calibration sets were 0.908 and 0.934 respectively. The coefficients of determination of validation sets were 0.961 and 0.952, the root mean square error of calibrations (RMSEC) was 0.184 and 0.136, and the root mean square error of predictions (RMSEP) was all 0.111 6. They conform to the model application requirement. At the same time, frying oil and qualified edible oil were identified with the principal component analysis (PCA), and the accurate rate was 100%. The experiment proved that near infrared spectral technology not only can quickly and accurately identify hogwash oil, but also can quantitatively detect hog- wash oil. This method has a wide application prospect in the detection of oil.

[The initial CT findings in patients suffering from invasive pulmonary aspergillosis].

OBJECTIVE: To approach the initial CT findings of invasive pulmonary aspergillosis (IPA) in patients with immunosuppression. METHODS: All consecutive adult patients who met the diagnostic criteria of the 2008 European Organization for Research and Treatment of Cancer/ Mycoses Study Group (EORTC/MSG) for proven or probable IPA were included as of January 2005 to June 2011. The patients were divided into two groups according to patients with or without hematological malignancy. The initial CT findings in our study were retrospectively reviewed by two thoracic radiologists, while patients' demographics and clinical outcomes were blinded. The pattern and number of abnormalities were recorded. RESULTS: A total of 65 IPA patients were eligible, with 34 hematological malignancy patients and 31 non-hematological patients. Among all IPA patients, the pattern of ground-glass opacity and consolidation or mass formation was most commonly seen (56.9%), followed by macronodules (46.2%); halo sign (32.3%) was relatively uncommon. Ground-glass opacity and consolidation or mass formation were more commonly identified in non-hematological patients than in hematological malignancy patients (54.8%, 45.2% vs. 8.8%, both P<0.05), but macronodules, infarct-shaped macronodules and halo signs were less frequently identified in the non-hematological group (16.1%, 3.2%, 12.9%, respectively) than in the hematological malignancy group (73.5%, 23.5% and 50.0%, respectively, P<0.05 or P<0.01). The airway-invasive form of IPA was more frequently seen in non-hematological patients (67.8%), whereas the angioinvasive form was more common in hematological malignancy patients (64.7%, P<0.01). CONCLUSION: Our data indicate that CT findings of IPA in non-hematological patients more commonly present as the airway-invasive form, manifesting ground-glass opacity and consolidation or mass formation, whereas in patients with hematological malignancy it more likely shows evidence of the angioinvasive form with macronodules and halo signs.

[Acting mechanisms and research methods of long noncoding RNAs].

Long non-coding RNAs (lncRNAs) play biological roles through a variety of mechanisms, including genetic imprinting, chromatin remodeling, cell cycle control, splicing regulation, mRNA decay, and translational regulation. LncRNAs are involved in the regulation of gene expression through the above mechanisms in different levels. Establishment and application of research technologies are important in understanding of lncRNAs functions. Microarray, RNA sequencing, Northern blot, real time quantitative reverse transcription-polymerase chain reaction, fluorescence in situ hybridization, RNA interference, and RNA-binding protein immunoprecipitation are major tools of exploring biological functions of lncRNAs. Here, we highlighted three advanced methods, i.e., fast predictions of RNA and protein interactions and domains (catRAPID), chromatin isolation by RNA purification (ChIRP), and combined knockdown and localization analysis of non-coding RNAs (c-KLAN).

Magnetic resonance tumor targeting imaging using gadolinium labeled human telomerase reverse transcriptase antisense probes.

To develop a molecular probe for MRI detection of human tumor telomerase reverse transcriptase (hTERT) mRNA expression. Uniformly phosphorothioate-modified hTERT antisense oligonucleotide (ASON) homing hTERT mRNA was labeled with gadolinium (Gd) through the bifunctional chelator 1,4,7, 10-tetraazacyclododecane-N, N', N'', N'''-tetraacetic acid (DOTA) stirred within 45 minutes at 60 °C. The Gd labeled probes were characterized in vitro. The cellular uptake rate and biodistribution of (99m) Tc-DOTA-ASON was measured instead of that of Gd-DOTA-ASON. A549 lung adenocarcinoma model was established in BALB/c nude mice and Gd-DOTA-ASON was injected intraperitoneally and MR images were acquired using 7.0T Micro-MRI (Bruker Biospec, Ettlingen, Germany) at different time points. Immunohistochemical analysis of telomerase activity of each xenograft was operated two days after in vivo imaging. The binding efficiency of Gd-DOTA-ASON reached as high as 71.7 ± 4.5% (n = 6). Gd-DOTA-ASON displayed perfect stability in fresh human serum at 37 °C for 24 h. Compared with normal lung cells, A549 cells showed an obviously higher uptake of (99m) Tc-DOTA-ASON than that of lung cells (10.5 ± 2.7% vs. 4.8 ± 2.6%, P < 0.05). The signal intensity of A549 xenografts can be enhanced by Gd-DOTA-ASON and the signal to noise ratio (SNR) of tumor to muscle reached 2.37 and maintained a relatively high level within 6 h after injection. The activity of hTERT in A549 tumors can be suppressed by Gd-DOTA-ASON in pathological slices. The results of this study show that Gd-DOTA-ASON can be a promising intracellular MR contrast probe for targeting telomerase-positive carcinomas.

Growth inhibitory effect of 4-phenyl butyric acid on human gastric cancer cells is associated with cell cycle arrest.

AIM: To investigate the growth effects of 4-phenyl butyric acid (PBA) on human gastric carcinoma cells and their mechanisms. METHODS: Moderately-differentiated human gastric carcinoma SGC-7901 and lowly-differentiated MGC-803 cells were treated with 5, 10, 20, 40, and 60 µmol/L PBA for 1-4 d. Cell proliferation was detected using the MTT colorimetric assay. Cell cycle distributions were examined using flow cytometry. RESULTS: The proliferation of gastric carcinoma cells was inhibited by PBA in a dose- and time-dependent fashion. Flow cytometry showed that SGC-7901 cells treated with low concentrations of PBA were arrested at the G0/G1 phase, whereas cells treated with high concentrations of PBA were arrested at the G2/M phase. Although MGC-803 cells treated with low concentrations of PBA were also arrested at the G0/ G1 phase, cells treated with high concentrations of PBA were arrested at the S phase. CONCLUSION: The growth inhibitory effect of PBA on gastric cancer cells is associated with alteration of the cell cycle. For moderately-differentiated gastric cancer cells, the cell cycle was arrested at the G0 /G1 and G2/M phases. For lowly-differentiated gastric cancer cells, the cell cycle was arrested at the G0/G1 and S phases.

Silencing of survivin gene in Jeko-1 cell line with small interfering RNA / 中国实验血液学杂志

This study was aimed to investigate the impact of specific siRNA on survivin gene in transfected lymphoma cell line and provide experimental evidences for future treatment of mantle cell lymphoma. The small interfering RNA (siRNA) targeted survivin mRNA was synthesized in vitro and was transfected into Jeko-1 that showed high survivin expression in mRNA level. The levels of survivin mRNA and protein expression were detected by quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot respectively. The apoptosis effect was examined by calculating the ratio of Annexin V-FITC/PI positive cells using flow cytometry. The inhibition of cell proliferation was assayed with CCK-8 reagent after transfection. The results showed that expression of survivin mRNA was markedly suppressed by the siRNA. The relative expression levels were 0.49 ± 0.03, 0.38 ± 0.02 and 0.17 ± 0.02 at time points of 24, 48 and 72 h respectively, compared with the control group; the inhibitive rates of cell proliferation were (31.2 ± 2.1)%, (43.3 ± 3.4)% and (52.6 ± 2.5)%; the apoptotic rates of cells were (6.3 ± 0.5)%, (13.5 ± 1.1)% and (23.6 ± 1.6)% respectively; survivin protein expression levels were gradually reduced. It is concluded that the siRNA targeting survivin down-regulates the expressions of survivin mRNA and protein evidently. The siRNA of survivin displays the potent ability to inhibit the proliferation of lymphoma cell line Jeko-1; survivin may become a potential molecular target for the therapy of lymphoma in the future.

The effect of apoptosis induced by IL-21 in SUDHL-4 cell line and its mechanism / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the apoptosis effect of diffuse large B-cell lymphoma cell line (DLBCL) SUDHL-4 induced by IL-21 and its related mechanism.</p><p><b>METHODS</b>SUDHL-4 cells were treated with IL-21 at different concentration (1000 ng/ml, 100 ng/ml, 10 ng/ml, 1 ng/ml) for 24 h, 48 h, 72 h, respectively. The inhibitory rate of cell proliferation was detected by CCK-8 assay. The cell growth curves were drawn and half inhibitory concentration (IC(50)) values were calculated. The cell apoptosis were detected by flow cytometry (FCM), the expression of the caspase-9, caspase-3, cleaved caspase-3, Bcl-2, Bcl-XL, Bid, Bax and c-myc protein in SUDHL-4 cells treated with IL-21 by western blot, the mRNA expression of Bcl-2, Bcl-XL, Bid, Bax, c-myc by Survivin gene with RT-PCR.</p><p><b>RESULTS</b>IL-21 markedly inhibited SUDHL-4 cell growth in a time- and dose-dependent manner. The 48 hIC(50) was 140.9ng/ml; The FCM showed that the apoptosis proportion of SUDHL-4 cells treated with 100 ng/ml of IL-21 apoptosis (AnnexinV-FITC(+) positive cells) gradually increased (48 h: 19.7 ± 2.3%). The protein expression of caspase-9, caspase-3, Bcl-2 and Bcl-XL decreased in a time-dependent manner. The Bax and c-myc protein markedly increased, but the Bid protein level did not change. IL-21 up regulated c-myc and Bax gene expression, however down regulated Bcl-2 and BCL-XL gene expression, but the gene expression of Bid and Survivin hadn't been changed significantly.</p><p><b>CONCLUSIONS</b>IL-21 can inhibit proliferation and induce apoptosis of SUDHL-4 cell. The mechanism may involve in endogenous mitochondrial pathway mediated by the c-myc and the Bcl-2 genes.</p>

piRNA, the new non-coding RNA, is aberrantly expressed in human cancer cells.

BACKGROUND: Piwi-interacting RNAs (piRNAs) are a novel class of non-coding single strand RNAs. They are involved in germline development, in silencing of selfish DNA elements, and in maintaining germline DNA integrity. The relationship between piRNAs and carcinogenesis has not been shown yet. METHODS: The relationship between piRNAs and carcinogenesis was identified by microarray screening and real-time quantitative reverse transcription-polymerase chain reaction technology. The piR-651 inhibitor was transfected into gastric cancer cells to assess its influence on cell growth. Cell cycle analysis was used to reveal the cellular mechanisms of piR-651 in the genesis of gastric cancer. RESULTS: piR-651 expression was upregulated in gastric cancer tissues compared with paired non-cancerous tissues. The levels of piR-651 were associated with TNM stage (P=0.032). The expression of piR-651 in gastric, colon, lung, and breast cancer tissues was higher than that in paired non-cancerous tissues. The upregulated expression of piR-651 was confirmed in several cancer cell lines including gastric, lung, mesothelium, breast, liver, and cervical cancer cell lines. The growth of gastric cancer cells was inhibited by a piR-651 inhibitor and arrested at the G(2)/M phase. CONCLUSION: piR-651 might be involved in the development of gastric cancer and other cancers, and is a potential marker for cancer diagnosis.

Telmisartan attenuates aortic hypertrophy in hypertensive rats by the modulation of ACE2 and profilin-1 expression.

Profilin-1 has recently been linked to vascular hypertrophy and remodeling. Here, we assessed the hypothesis that angiotensin (Ang) II type I receptor antagonist telmisartan improves vascular hypertrophy by modulation of expression of profilin-1 and angiotensin-converting enzyme 2 (ACE2). Ten-week-old male spontaneously hypertensive rats (SHR) were received oral administration of telmisartan (5 or 10mg/kg; daily) or saline for 10 weeks. Compared with Wistar-Kyoto (WKY) rats, there were marked increases in systolic blood pressure and profilin-1 expression and reduced ACE2 and peroxisome proliferator activated receptor-γ (PPARγ) levels in aorta of SHR, associated with elevated extracellular-signal regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) phosphorylation signaling and aortic hypertrophy characterized with increased media thickness, which were strikingly reversed by telmisartan. In cultured human umbilical artery smooth muscle cells (HUASMCs), Ang II induced a dose-dependent increase in profilin-1 expression, along with decreased ACE2 protein expression and elevated ERK1/2 and JNK phosphorylation. In addition, blockade of ERK1/2 or JNK by either specific inhibitor was able to abolish Ang II-induced ACE2 downregulation and profilin-1 upregulation in HUASMCs. Importantly, treatment with telmisartan (1 or 10 µM) or recombinant human ACE2 (2mg/ml) largely ameliorated Ang II-induced profilin-1 expression and ERK1/2 and JNK phosphorylation and augmented PPARγ expression in the cultured HUASMCs. In conclusion, telmisartan treatment attenuates vascular hypertrophy in SHR by the modulation of ACE2 and profilin-1 expression with a marked reversal of ERK1/2 and JNK phosphorylation signaling pathways.

Study of hypermethylation of SOCS gene in typical myeloproliferative disease / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical role of hypermethylation of suppressor of cytokine signaling (SOCS) on typical myeloproliferative disease (MPD) patients and its mechanism.</p><p><b>METHODS</b>Methylation specific PCR was used to detect SOCS1, 2, 3 methylation, direct DNA sequencing was performed to detect JAK2V617F mutation, real-time fluorescence quantitative PCR were applied to evaluate transcriptional activity of SOCS1, 2, 3.</p><p><b>RESULTS</b>Among 100 MPD patients, hypermethylation of SOCS1 was detected in 27 (27%), hypermethylation of SOCS2 in 9 (9%), hypermethylation of SOCS3 in 34 (34%); JAK2V617F mutation in 64 (64%). Hypermethylation of SOCS1, 3 greatly inhibited gene expression compared with unmethylated ones (P < 0.05). Presence of JAK2V617F mutation markedly down-regulated SOCS1, 3 gene mRNA expression compared with wild JAK2V617F (P < 0.05).</p><p><b>CONCLUSION</b>Hypermethylation of SOCS1, 3 and JAK2V617F mutation exist in MPD, which inhibited SOCS1, 3 gene expression. SOCS hypermethylation and JAK2V617F mutation can activate JAK-STAT signaling pathways, these observations may provide a potential therapeutic direction.</p>

The distribution and scintigraphy of 99Tcm labeled NGR-interferon-alpha2a in tumor bearing mice / 中华核医学杂志

Objective To sythesize 99Tcm labeled asparagine-glycine-arginine (NGR)- interferon (INF)-α2a and investigate its biodistribution by scintigraphy in tumor bearing mice. Methods NGR-INFα2a was labeled with 99Tcm by a two-step method. Ethylenedicysteine (EC) and MDP were used as bifunctional and transferring chelating agents. The bioactivities of 99Tcm-NGR-IFN-EC-NGR-IFN-α2a, EC-NGRIFN-α2a and NGR-IFN-α2a were compared using least significant difference t-test. The hepatoma bearing mice models were established by subcutaneous injection of MHCC97-H cells. The mice were randomly divided into eight groups and 7.4 MBq 99Tcm-NGR-IFN-α2a was injected via the tail vein. The tissue uptake of the radiolabeled compound was measured as % ID/g. The scintigraphy was performed at 0.5, 1, 2, 4,6, 8, 12 and 24 h after injection. ROI were drawn around tumor and non-tumor tissue and the radioactivity ratio of T/NT was calculated. Results Both the labeling efficiency and radiochemical purity of 99Tcm-EC-NGR-IFN-α2a were more than 90%. The radiochemical purity was 71% after 24 h in saline. The bioactivity showed no significant difference among three compounds (t = 0.416, 0. 120 and 1. 300, all P >0.05). The tracer was mainly excreted through alimentary and urinary tract within 24 h after injection. The peak values of % ID/g in kidney, liver, interstinal tract and tumor were 41.5 ± 8.0_ (at 8 h), 31.3 ± 5.0(at 6 h), 36.0 ± 7.8 (at 6 h), 43.0 ± 4.8 (at 4 h), respectively. The tracer was cleared quickly from the blood and the highest T/NT ratio was 16.5. The optimal imaging time ranged from 4 to 8 h after injection. Conclusions The sythesis of 99Tcm-NGR-IFN-α2a is applicable and it may be used as a potential tumor imaging agent.

[Effect of microRNA on proliferation of human tongue carcinoma Tca8113 cells].

OBJECTIVE: To investigate the effects of microRNA (miRNA) on proliferation of cultured human squamous cell carcinoma of tongue Tca8113 cells. METHODS: The mimics or inhibitors of miRNA-31 or miRNA-139 were transfected into Tca8113 cells using liposome. Tca8113 cell proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. RESULTS: The absorbance (A) values of control group at 24 h, 48 h and 72 h were 0.125 +/- 0.002, 0.169 +/- 0.002 and 0.216 +/- 0.004, respectively. The mimics of miRNA-31 increased Tca8113 cell proliferation, with A values increasing to 0.136 +/- 0.001 (P < 0.001), 0.186 +/- 0.004 (P < 0.001) and 0.249 +/- 0.012 (P < 0.01), respectively. The inhibitors of miRNA-139 also increased A values to 0.148 +/- 0.002 (P < 0.001), 0.214 +/- 0.002 (P < 0.001) and 0.250 +/- 0.009 (P < 0.01), respectively. Contrast with these results, the inhibitors of miRNA-31 decreased Tca8113 cell proliferation, with A values decreasing to 0.145 +/- 0.001 and 0.155 +/- 0.011 (both of P < 0.001) at 48 h and 72 h, respectively. The mimics of miRNA-139 also decreased A to 0.135 +/- 0.001 and 0.170 +/- 0.009 (both of P < 0.001). CONCLUSIONS: miRNA-31 and miRNA-139 play an important role in the carcinogenesis of human tongue carcinomas. It may become a new method for the treatment of tongue carcinomas by adjustment the activities of miRNA.