Hydrogen Sulfide Regulating Myocardial Structure and Function by Targeting Cardiomyocyte Autophagy.

OBJECTIVE: Hydrogen sulfide (H2S), a gaseous signal molecule, plays a crucial role in many pathophysiologic processes in the cardiovascular system. Autophagy has been shown to participate in the occurrence of many cardiac diseases. Increasing evidences indicated that H2S regulates myocardial structure and function in association with the altered autophagy and plays a "switcher" role in the autophagy of myocardial diseases. The aim of this review was to summarize these insights and provide the experimental evidence that H2S targets cardiomyocyte autophagy to regulate cardiovascular function. DATA SOURCES: This review was based on data in articles published in the PubMed databases up to October 30, 2017, with the following keywords: "hydrogen sulfide," "autophagy," and "cardiovascular diseases." STUDY SELECTION: Original articles and critical reviews on H2S and autophagy were selected for this review. RESULTS: When autophagy plays an adaptive role in the pathogenesis of diseases, H2S restores autophagy; otherwise, when autophagy plays a detrimental role, H2S downregulates autophagy to exert a cardioprotective function. For example, H2S has beneficial effects by regulating autophagy in myocardial ischemia/reperfusion and plays a protective role by inhibiting autophagy during the operation of cardioplegia and cardiopulmonary bypass. H2S postpones cardiac aging associated with the upregulation of autophagy but improves the left ventricular function of smoking rats by lowering autophagy. CONCLUSIONS: H2S exerts cardiovascular protection by regulating autophagy. Cardiovascular autophagy would likely become a potential target of H2S therapy for cardiovascular diseases.

[Pollution Characteristics and Source Analysis of Polycyclic Aromatic Hydrocarbons in Agricultural Soils from Shandong].

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants that originate mainly from anthropogenic sources. PAHs have elicited much concern because they exhibit strong toxic, carcinogenic, and mutagenic properties. Agricultural soil is at risk of PAH contamination mainly caused by atmospheric depositions, wastewater irrigation, or organic substances and biowaste applied as fertilizers. The surface agricultural soils were collected from Shandong in July 2015, and measured for 16 US EPA priority PAHs using high performance liquid chromatography with UV and fluorescence detector. The content and composition of PAHs were analyzed. The differences of PAHs between soils from the field for growing crops and from vegetable greenhouses, and between soils from point sources and from non-point sources were compared. The sources of PAHs were determined with methods of ratio between PAHs and positive matrix factorization (PMF), and the risks of PAHs were assessed. The results showed that the total content of 16 PAHs (∑16PAHs) ranged from 111.5 ng·g-1 to 2744.1 ng·g-1, with the mean of 556.3 ng·g-1. The content of 3-ring PAHs was relatively high, with the mean of 201.5 ng·g-1; while the contents of 2-ring and 6-ring PAHs were relatively low, with the mean of 39.3 ng·g-1 and 43.4 ng·g-1, respectively. According to the contamination classification in Poland, 71% of the samples in Shangdong were weakly contaminated. Compared with other areas in China, the content of PAHs in the agricultural soils in Shandong was in the middle range. Acenaphthene, fluorine, and fluoranthene were the major PAH compounds, accounting for more than 10% of the total PAHs; while the contribution of indeno (1,2,3-cd) pyrene was low. The content of ∑16PAHs and contribution of 7 carcinogenic PAHs were significantly higher in soils polluted by point sources than those in soils from non-point sources. Moreover, the contribution of PAHs with 2-3 rings was significantly higher in soils from non-point sources, while the contribution of PAHs with 4-6 rings was significantly higher in soils polluted by point sources. There was no significant difference in soils from vegetable greenhouses and from adjacent field soils, and the contribution of PAHs with 3-4 rings was high. The PAH isomer pair ratios of Ant/(Ant+Phe), Flu/(Flu+Pyr), BaA/(BaA+Chr), and InP/(InP+BP) were utilized as molecular indices to elucidate the possible PAH sources, and the results suggested that the PAHs in the soils were mainly from combustion. To quantitatively assess the contribution of various sources to PAH contamination, PMF was used to analyze the sources. The sources of PAHs were combustion of coal biomass, oil combustion from traffic, coking, and petroleum pollution, with contribution of 42.7%, 19.3%, 22.8% and 15.2%, respectively. Toxic equivalency factors were used to evaluate PAH contamination in the soils, and the carcinogenicity of other PAHs relative to BaP was quantified to estimate the BaP-equivalent concentration (TEQBaP). The TEQBaPof 16 PAHs (∑16TEQBap) in soils from non-point sources and vegetable greenhouses was 31.69 and 44.47 ng·g-1, respectively, which were below the safe value in Canadian soil quality guidelines. However, the ∑16TEQBap in some field soils from point sources exceeded the safe value, indicating that there were potential risks in the soils from point sources in Shandong.

[Relation between Chinese Medical Constitutions and Chemotherapy-induced Leucopenia in Breast Cancer Patients: a Clinical Study].

OBJECTIVE: To analyze the relationship between Chinese medical constitutions and chemotherapy-induced leucopenia (CIL) of primary breast cancer patients. METHODS: Totally 306 breast cancer patients undergoing adjunctive chemotherapy for the 1st time, and effective 291 breast cancer patients were recruited in this study.Nine Basic Constitutional Scale was used before first chemotherapy. Chinese medical constitutions were classified and quantitatively scored. The highest grading for any item of adverse reactions in each case during the whole chemotherapy course was recorded after chemotherapy. Data were statistically analyzed using SPSS16.0. RESULTS: There was no significant difference in CIL between different chemotherapy regimens and various Chinese medical constitutions of breast cancer patients (P > 0.05). Yang deficiency constitution is one risk factor for CIL. The higher the score of yang deficiency constitution, the more severe the CIL. CONCLUSIONS: Yang deficiency constitution was correlated with the degree of CIL. The higher the score of yang deficiency constitution, the greater the risk of III-IV grade CIL in breast cancer patients.

Improved performance in differentiating benign from malignant sinonasal tumors using diffusion-weighted combined with dynamic contrast-enhanced magnetic resonance imaging.

BACKGROUND: Differentiating benign from malignant sinonsal lesions is essential for treatment planning as well as determining the patient's prognosis, but the differentiation is often difficult in clinical practice. The study aimed to determine whether the combination of diffusion-weighted (DW) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can improve the performance in differentiating benign from malignant sinonasal tumors. METHODS: This retrospective study included 197 consecutive patients with sinonasal tumors (116 malignant tumors and 81 benign tumors). All patients underwent both DW and DCE-MRI in a 3-T magnetic resonance scanner. Two different settings of b values (0,700 and 0,1000 s/mm 2 ) and two different strategies of region of interest (ROI) including whole slice (WS) and partial slice (PS) were used to calculate apparent diffusion coefficients (ADCs). A DW parameter with WS ADCs b0,1000 and two DCE-MRI parameters (time intensity curve [TIC] and time to peak enhancement [Tpeak]) were finally combined to use in differentiating the benign from the malignant tumors in this study. RESULTS: The mean ADCs of malignant sinonasal tumors (WS ADCs b0,1000 = 1.084 × 10-3 mm 2 /s) were significantly lower than those of benign tumors (WS ADCs b0,1000 = 1.617 × 10-3 mm 2 /s, P < 0.001). The accuracy using WS ADCs b0,1000 alone was 83.7% in differentiating the benign from the malignant tumors (85.3% sensitivity, 81.2% specificity, 86.4% positive predictive value [PPV], and 79.5% negative predictive value [NPV]). The accuracy using DCE with Tpeak and TIC alone was 72.1% (69.1% sensitivity, 74.1% specificity, 77.5% PPV, and 65.1% NPV). Using DW-MRI parameter was superior than using DCE parameters in differentiation between benign and malignant sinonasal tumors (P < 0.001). The accuracy was 87.3% (90.5% sensitivity, 82.7% specificity, 88.2% PPV, and 85.9% NPV) using DW-MRI combined with DCE-MRI, which was superior than that using DCE-MRI alone or using DW-MRI alone (both P < 0.001) in differentiating the benign from the malignant tumors. CONCLUSIONS: Diffusion-weighted combined with DCE-MRI can improve imaging performance in differentiating benign from malignant sinonasal tumors, which has the potential to improve diagnostic accuracy and to provide added value in the management for these tumors.

Silencing airway epithelial cell-derived hepcidin exacerbates sepsis induced acute lung injury.

INTRODUCTION: The production of antimicrobial peptides by airway epithelial cells is an important component of the innate immune response to pulmonary infection and inflammation. Hepcidin is a ß-defensin-like antimicrobial peptide and acts as a principal iron regulatory hormone. Hepcidin is mostly produced by hepatocytes, but is also expressed by other cells, such as airway epithelial cells. However, nothing is known about its function in lung infectious and inflammatory diseases. We therefore sought to investigate the role of airway epithelial cell-derived hepcidin in sepsis-induced acute lung injury. METHODS: Acute lung injury was induced by polymicrobial sepsis via cecal ligation and puncture (CLP) surgery. Adenovirus-mediated short hairpin RNA specific for the mouse hepcidin gene hepc1 and control adenovirus were intratracheally injected into mice. The adenovirus-mediated knockdown of hepcidin in airway epithelial cells was evaluated in vivo. Lung injury and the 7-day survival rate were assessed. The levels of hepcidin-related iron export protein ferroportin were measured, and the iron content and function of alveolar macrophages were evaluated. RESULTS: The hepcidin level in airway epithelial cells was upregulated during polymicrobial sepsis. The knockdown of airway epithelial cell-derived hepcidin aggravated the polymicrobial sepsis-induced lung injury and pulmonary bacterial infection and increased the mortality (53.33% in Ad-shHepc1 treated mice versus 12.5% in Ad-shNeg treated mice, P <0.05). The knockdown of hepcidin in airway epithelial cells also led to reduced ferroportin degradation and a low intracellular iron content in alveolar macrophages. Moreover, alveolar macrophages form the airway epithelial cell-derived hepcidin knockdown mice showed impaired phagocytic ability than those from the control mice. CONCLUSIONS: Airway epithelial cell-derived hepcidin plays an important role in CLP induced acute lung injury. The severe lung injury in the airway epithelial cell-derived hepcidin knockdown mice is at least partially related to the altered intracellular iron level and function of alveolar macrophages.

Anti-tumor effects of brucine immuno-nanoparticles on hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma is difficult to diagnose early, and most patients are already in the late stages of the disease when they are admitted to hospital. The total 5-year survival rate is less than 5%. Recent studies have showed that brucine has a good anti-tumor effect, but high toxicity, poor water solubility, short half-life, narrow therapeutic window, and a toxic dose that is close to the therapeutic dose, which all limit its clinical application. This study evaluated the effects of brucine immuno-nanoparticles (BIN) on hepatocellular carcinoma. MATERIALS AND METHODS: Anionic polymerization, chemical modification technology, and phacoemulsification technology were used to prepare a carboxylated polyethylene glycol-polylactic acid copolymer carrier material. Chemical coupling technology was utilized to develop antihuman AFP McAb-polyethylene glycol-polylactic acid copolymer BIN. The size, shape, zeta potential, drug loading, encapsulation efficiency, and release of these immune-nanoparticles were studied in vitro. The targeting, and growth, invasion, and metastasis inhibitory effects of this treatment on liver cancer SMMC-7721 cells were tested. RESULTS: BIN were of uniform size with an average particle size of 249 ± 77 nm and zeta potential of -18.7 ± 4.19 mV. The encapsulation efficiency was 76.0% ± 2.3% and the drug load was 5.6% ± 0.2%. Complete uptake and even distribution around the liver cancer cell membrane were observed. CONCLUSION: BIN had even size distribution, was stable, and had a slow-releasing effect. BIN targeted the cell membrane of the liver cancer cell SMMC-7721 and significantly inhibited the growth, adhesion, invasion, and metastasis of SMMC-7721 cells. As a novel drug carrier system, BIN are a potentially promising targeting treatment for liver cancer.

[Mesenchymal stem cells implantation increases the myofibroblasts congregating in infarct region in a rat model of myocardial infarction].

OBJECTIVE: To investigate the modulation effects of mesenchymal stem cells (MSC) implantation on the myofibroblasts congregating in the infarct region after myocardial infarction (MI). METHODS: MI was induced in SD rats by left anterior descending coronary artery ligation, and the experimental animals were assigned randomly into the sham group, MI + PBS group and MI + MSC group (myocardial injection of 0.1 ml 2×10(7)/ml in four locations in the infarct region). Echocardiography, hemodynamic examinations and Masson trichrome staining were performed. Implanted MSC differentiation and myofibroblasts congregating in infarct region were investigated by immunofluorescence staining. TGF-ß(1)-Smad2 signaling pathway was examined by real-time RT-PCR and Western blot. RESULTS: (1) Four weeks late, heart-weight/body-weight ratio [(3.04 ± 0.16) mg/g vs. (3.34 ± 0.14) mg/g, P < 0.01] and myocardial infarction size [(38.72 ± 2.38)% vs. (46.36 ± 2.81)%, P < 0.01] were significantly reduced in MI + MSC group than in MI + PBS group, while scar thickness of infarct region was thicker [(0.93 ± 0.17) mm vs. (0.65 ± 0.16) mm, P = 0.01], and LVEF was higher [LVEF: (32.5 ± 5.9)% vs. (26.5 ± 4.5)%, P = 0.03] in MI + MSC group than in MI + PBS group. (2) Myofibroblasts congregating in the infarct region was significantly enhanced in MI + MSC group compared with MI + PBS group [(196 ± 20) cells/mm(2) vs. (89 ± 25) cells/mm(2), P < 0.01], and part of implanted MSC expressed α-SMA(+). (3) TGF-ß(1) expression and the phosphorylating of Smad2 in the infarct region were significantly upregulated in MI + MSC group compared with MI + PBS group (all P < 0.05). CONCLUSIONS: MSC could improve myocardial function and promote myofibroblasts congregating in the infarct region via activating the TGF-ß(1)-Smad2 signaling pathway in this model.

[Influence of nano-silica content on flexural properties of the aluminum borate whisker and silica filler composite resins].

OBJECTIVE: To discuss the influence of nano-silica content which was hydrolyzed by tetraethyl orthosioate (TEOS) on the aluminum borate whisker (AlBw) and silica filler composite resins on flexural properties. METHODS: The nanometer-size silicon dioxide (SiO2) particles were prepared by sol-gel method based on tetraethyl orthosioate. Different proportion of AlBw and SiO2 were fused and attached onto the surface of AlBw through high temperature, then polymerized with resin matrix after surface siliconization and their flexural strength and flexural modulus were determined. The effects of heat treatment to the surface morphology of AlBw and the shapes of the mixture at various proportions were characterized by TEM. RESULTS: The flexural properties of dental composite resins with AlBw-SiO2 compound as inorganic fillers were significantly improved. The flexural property of a new type of dental composite resins was(130.29 +/- 8.38) MPa, when the mass ratio of AlBw and nano-SiO2 particle was 3:1. CONCLUSION: Nano-silica content which was hydrolyzed by tetraethyl orthosioate improved flexural properties of the aluminum borate whisker and silica filler composite resins.

[Dural modulation effects of mesenchymal stem cells implantation on myocardial collagen remodeling in a rat model of myocardial infarction].

OBJECTIVE: To investigate the modulation effects of mesenchymal stem cells (MSCs) implantation on the collagen remodeling in myocardial infarction. METHODS: Acute myocardial infarction (AMI) was induced in SD rats by left anterior descending coronary artery ligation, and the animals were assigned randomly into the Sham group, MI + PBS group and MI + MSCs group. Echocardiography and hemodynamic examinations were performed to evaluate the cardiac function. HE staining and Masson trichrome staining were used to evaluate the myocardial infarction size. Infarcted area and infarcted expansion index were calculated. The expression of collagens in infarcted hearts was evaluated by immunohistochemistry, RT-PCR and Western blot. RESULTS: (1) Infarct area was significantly reduced post MSCs transplantation [MI + MSCs vs. MI + PBS: (38.27 ± 2.70)% vs. (46.20 ± 3.17)%, P < 0.001]. (2) Cardiac function was significantly improved post MSCs transplantation [MI + MSCs vs. MI + PBS: FS(%): 29.98 ± 4.50 vs. 23.43 ± 3.34, P = 0.005; LVSP (mm Hg, 1 mm Hg = 0.133 kPa): 113.63 ± 10.81 vs. 99.25 ± 16.76, P < 0.05; LVEDP (mm Hg): 12.10 ± 4.28 vs. 20.08 ± 4.26, P < 0.05; +dp/dtmax (mm Hg/s): 4616.63 ± 363.34 vs. 3912.75 ± 248.79, P < 0.05; -dp/dtmax (mm Hg/s): 4254.63 ± 324.34 vs. 3530.88 ± 309.71, P < 0.05]. (3) Collagen synthesis was enhanced in infarcted area and decreased in non-infarcted area post MSCs transplantation (P < 0.05). CONCLUSIONS: MSCs transplantation could enhance the collagen synthesis in infarcted area while decrease the deposition of collagen in non-infarcted area in this MI model. This may be one of the mechanisms by which ventricular remodeling is attenuated post MSCs transplantation.

[The inhibitory effect of paclitaxel nanoparticles on ovarian cancer xenografts and lymphatic targeting].

OBJECTIVE: To develop a polymeric drug delivery system for paclitaxel and determine whether paclitaxel can inhibit the growth of ovarian carcinoma xenografts in F344 rats by intraperitoneal administration. METHODS: Paclitaxel loading nanoparticles (PLA) were synthesized by ultrasonic emulsification; rat ovarian carcinoma cells were injected into the peritoneal cavity of F344 rats. The antitumor effect of paclitaxel nanoparticles in vivo has been evaluated by measuring tumor weight and ascite volume. At the end of the procedure the rats were killed, tumors were excised and processed for PCNA staining, tissue terminal deoxynucleotide transferase-mediated dUTP nick and labeling (TUNEL) assay. Paclitaxel concentration in plasma, pelvic lymph nodes, liver, heart were determined by high-performance liquid chromatography (HPLC). RESULTS: In the implanted carcinoma cells, paclitaxel nanoparticles significantly reduced tumor weight [(4.55 +/- 0.11) g vs (10.13 +/- 0.52) g]and ascites volume [(3.55 +/- 0.50) mL vs (30.45 +/- 1.55) mL], and induced apoptosis of tumor cells [(105 +/- 15) vs (55 +/- 10)]. The paclitaxel concentration of pelvic lymph nodes in PLA treated animals was significantly higher than that of free PTX treated animals 48 h after intraperitoneal administration [(0.75 +/- 0.05) microg/g vs (0.188 +/- 0.045) microg/g]. CONCLUSION: The intraperitoneal administration of paclitaxel nanoparticles can significantly inhibit the progression of ovarian carcinoma in peritoneal cavity of female F344 rats. The paclitaxel nanoparticle is safe and lymphatic targeting.

[Mutation screening of RET proto-oncogene in Chinese sporadic patients with pheochromocytoma].

OBJECTIVE: To screen the mutations of RET proto-oncogene in sporadic patients with pheochromocytoma. METHODS: Forty-two cases of sporadic pheochromocytoma were tested for mutations of RET gene. Of these 42 DNA samples, 12 were extracted from peripheral blood cells and 30 from paraffin-embedded pheochromocytoma specimens. The PCR product of exon 10 and exon 11 was used to molecular analysis of the RET proto-oncogene. RESULTS: Among 42 patients, 2 were found to have RET gene mutations. One of mutations located at codon 634 (TGC>TAC) in exon 11 of RET proto-oncogene. Another one located at codon 632 (GAG>AAG). CONCLUSION: Some patients with apparently sporadic pheochromacytoma were carrier of mutations, a routine genetic analysis for mutations of RET gene is indicated for these patients.