M2 tumor-associated macrophages and CXCL2 induce lipid remodeling in hepatocellular carcinoma cell lines.

Primary hepatocellular carcinoma (HCC) is one of the most common malignant tumors, but its pathogenesis remains incompletely elucidated. Recently, many studies indicated that lipid remodeling plays an important role in the occurrence and development of HCC. Furthermore, lipids have been proven to be indispensable mediators in promoting communication between tumor cells and extracellular matrix in the tumor microenvironment. Thus, this study aims to comprehensively investigate the process of lipid remodeling during HCC metastasis based on the LC-electrospray ionization-MS (LC-ESI-MS) combined with multiple reaction monitoring technology. M2 tumor-associated macrophages and the recombinant human protein CXCL2 were used to simulate the tumor microenvironment. After co-incubating SMMC7721 and MHCC97-H cell lines with M2 tumor-associated macrophages or the recombinant human protein CXCL2 for 48 h, LC-ESI-MS was used to quantify the levels of two major classes of lipid molecules, namely, glycerophospholipids and sphingolipids. Our results suggest that lipid remodeling in the tumor microenvironment may promote the migration and invasion of HCC cell lines.

[Study on safflower yellow for injection based on cell degranulation and acute anaphylactoid model].

This paper was aimed to establish screening methods of anaphylactoid reaction caused by safflower yellow for injection based on RBL-2 H3 cell degranulation model and mice model for acute anaphylactoid reaction,and evaluate the hypersensitivity caused by safflower yellow for injection from different batches. An in vitro cell model was used to keep the cells stimulated for an hour with different batches of safflower yellow for injection as the drug group,serum-free MEM medium as negative control group and 30 mg·L-1 C48/80 as positive control group respectively. The supernatant was then absorbed,and neutral red staining technique was used to detect the effect of safflower yellow injection on the degranulation of RBL-2 H3 cells with the positive cell rate of degranulation as the indicator.An in vivo model was established to validate the experimental results,and mice model for acute anaphylactoid reaction and ELISA method were adopted to detect the plasma histamine content,and screen the hypersensitivity caused by safflower yellow for injection at the animal level by using plasma histamine content as a test index. The results of the neutral red staining experiments showed that the positive control C48/80 could cause cell degranulation,and most of the cells were deeply stained. There was significant difference in positive cell rate between different batches of safflower yellow and positive control group. In the mice model for acute anaphylactoid reaction,it was found that the positive control C48/80 significantly increased the histamine content in the plasma of mice,while the safflower yellow in each batch did not cause a significant increase in plasma histamine( P<0. 000 1). The mechanism of anaphylactoid reaction is relatively complicated. This study was mainly based on the release of histamine and other active substances by degranulation of mast cells. No significant degranulation reaction of RBL-2 H3 cells induced by safflower yellow for injection was detected,nor was the plasma histamine level significantly increased in mice from the in vitro and in vivo aspects.

[Algae-inhibitory effect and mechanism of plant source n-caprylic acid].

OBJECTIVE: To research the algae-inhibitory effect and mechanism of a plant source n-caprylic acid extracted from coconut oil on M. aeruginosa. METHODS: The M. aeruginosa were treated with 0, 12.5, 25, 50 and 100 µL/L densities of coconut oil n-caprylic acid respectively. And the change of algal density, cell permeability and antioxidant ability were measured. RESULTS: The greater the concentration of coconut oil n-caprylic acid, the stronger the inhibition on M. aeruginosa. When the concentration was 100 µL/L and processed time was 96 h, the inhibition ratio on M. aeruginosa reached 99%. Compared with the control group, the algal liquid conductivity, nucleic acid content and protein content of experimental groups increased significantly. The SOD activity enhanced with the increasing of coconut oil n-caprylic acid concentration (under 25 µL/L), but when beyond a certain concentration (exceed 25 µL/L), its activity weakened greatly. And the MDA content increased with the increasing of coconut oil n-caprylic acid concentration. CONCLUSION: Coconut oil n-caprylic acid has a significant inhibiting effect on M. aeruginosa. Its mechanism may be largely related to cell membrane permeability change and antioxidant capacity reducing.

Lipidomics analysis of bone marrow in a mouse model of postmenopausal osteoporosis.

Postmenopausal osteoporosis (PMOP) is a major public health problem worldwide, afflicting many postmenopausal women. Although many studies have focused on the biological role of individual lipids in osteoporosis, no studies have systematically elucidated the lipid profile of osteoporosis. In this study, liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology based on multiple reaction monitoring (MRM) method was used to compare the levels of lipid molecules in bone marrow cells of osteoporotic mice (OVX) group and sham-operation (Sham) group. Principal component analysis (PCA) was used for multivariate statistics. Differential lipids were obtained by bar graph, heatmap and volcano map. A total of 400 lipid molecules were identified. A total of 199 lipid molecules were identified to be associated with PMOP, including 6 phospholipids and 3 sphingolipids. These differential lipid molecules provide a systematic lipid profile for osteoporosis, which helps to discover new candidate osteoporosis biomarkers, and their changes at the molecular level can be used as new targets for diagnosis or prevention.

Light-Switchable Yolk-Mesoporous Shell UCNPs@MgSiO3 for Nitric Oxide-Evoked Multidrug Resistance Reversal in Cancer Therapy.

Gas therapy has emerged as a forceful strategy for augmenting the effects of chemotherapeutic drugs against cancer cells. However, it remains extremely challenging to effectively deliver gas into tissues of interest and unravel its underlying mechanisms. Herein, we designed a near-infrared (NIR) light-switchable nitric oxide (NO) delivery nanosystem for high-efficacy multidrug resistance (MDR) reversal in cancer therapy based on a yolk-shell upconverting nanoparticles@magnesium silica (UCNP@MgSiO3). The internal hollow cavity and flower-like mesoporous shell of UCNPs@MgSiO3 not only enabled a significantly high encapsulation capacity for the NO precursor (BNN6) and doxorubicin (DOX) but also allowed the enhanced cellular uptake, resulting in NIR-triggered NO generation and low pH-triggered DOX release in cancer cells. Mechanistically, intracellular NO can downregulate the drug efflux-related P-glycoprotein and adenosine 5'-triphosphate-binding cassette transporters, thereby increasing the DOX accumulation in the cell nuclei. Such combination therapy of NO and DOX induced the apoptosis of MDR cells and completely inhibited in vivo MDR tumor growth. We further elucidated the therapy mechanism via proteomic profiling, showcasing the downregulation of the ubiquitin-proteasome pathway and nuclear factor kappa-B signaling pathway in the NO-treated MDR cells. Therefore, our findings develop a promising nanoscale gas/drug delivery paradigm for fighting MDR tumors and providing molecular insights into cancer therapy.

Pulmonary invasive fungal disease and bacterial pneumonia: a comparative study with high-resolution CT.

BACKGROUND: Early diagnosis of invasive fungal disease (IFD) is challenging. High-resolution computed tomography (CT) may improve IFD diagnosis; however, there are no definitive imaging signs for differentiating between bacterial pneumonia and IFD. METHODS: We retrospectively evaluated CT images of 208 patients with IFD (n = 102) or bacterial pneumonia (n = 106). We classified pulmonary opacities as consolidations, ground-glass opacities (GGOs), or nodules and recorded the presence of perinodular ground-glass halos, reversed halo sign (RSH), and cavitation (crescent-shaped or not). RESULTS: Consolidation appeared in 83.3% and 92.5% of patients with IFD and bacterial pneumonia, respectively. Multifocal non-segmental consolidation was more common in IFD (48%) than bacterial pneumonia (22.6%; P < 0.05). Segmental or subsegmental consolidation was more common in bacterial pneumonia (43.4%) than IFD (7.8%; P < 0.01). GGOs and nodules were more common in IFD than bacterial pneumonia (60.8% vs. 24.5% and 54.9% vs. 15.1%, respectively; each P < 0.05). Consolidation combined with GGO, nodules, or both GGO and nodules was more frequent in IFD than in bacterial pneumonia (each P < 0.05). Nodules with halo sign (n = 23) appeared in 22.5% and 3.8% of patients with IFD and bacterial pneumonia, respectively. Nodules with RSH appeared only in IFD, and those with cavitation appeared in 11.8% and 1.9% of patients with IFD and bacterial pneumonia, respectively. CONCLUSIONS: Consolidation plus GGO and nodules or consolidation plus nodules is suggestive for IFD. Segmental or subsegmental consolidations are more frequent in bacterial pneumonia than in IFD. Large nodules, as well as nodules with halo sign or both small and large nodules, are related to IFD.

Protective cerebrovascular effects of hydroxysafflor yellow A (HSYA) on ischemic stroke.

The purpose of the present work was designed to explore protective cerebrovascular effects of hydroxysafflor yellow A (HSYA), and provide preclinical efficacy and mechanism data for its possible application in patients with cerebral ischemia. The protective effect of HSYA on ischemic stroke was evaluated by infarct sizes and neurological scores in Sprague-Dawley (SD) rats with middle cerebral artery occlusion (MCAO). Cerebrovascular permeability was detected by Evans blue dye leakage in MCAO rats. Cerebral blood flow, as well as blood pressure and heart rate were monitored using flow probes in Beagle dogs. Basilar artery tension isolated from Beagle dogs was evaluated with an MPA 2000 data-acquisition system. Coagulation-related function was also judged, including rabbit platelet aggregation by adenosine diphosphate (ADP) and platelet-aggregating factor (PAF), rabbit blood viscosity by a blood viscometer, and thrombus formation by rat arterial-venous shunts. Results showed that HSYA treatment significantly decreased the infarct sizes, neurological scores and cerebrovascular permeability in rats with MCAO. However, cerebral blood flow, blood pressure and heart rate were not affected by HSYA. In vitro, HSYA had a strong effect on cerebrovascular vasodilatation, and significantly decreased platelet aggregation, blood viscosity, and thrombogenesis. Besides well-known anti-coagulation effects, HSYA protects against ischemic stroke by dilating cerebral vessels and improving cerebrovascular permeability.

mRNA expression of glucocorticoid receptor and serological and virological markers of chronic hepatitis B.

Glucocorticoid receptor (GR) function is essential for glucocorticoid action on various effector cells. The aim of the present study was to investigate the mRNA expression profiles of GRα and GRß in peripheral blood mononuclear cells (PBMC) and examine the association between the expression levels of the GR isoforms and the serological and virological hepatitis B virus (HBV) status in patients with chronic hepatitis B (CHB). A total of 29 CHB patients were examined in the present study, which were divided into subgroups according to serological and virological markers. The levels of GRα and GRß in PBMCs, HBV viral loads, HBV surface antigen (HBsAg), HBV e antigen (HBeAg) and pre­S1Ag were measured. A total of 43 healthy individuals served as controls. GRα was present in the PBMCs of all CHB patients and healthy controls, whereas GRß­specific products were present in only 93.1% of the CHB patients and 86.0% of the healthy controls. The GRα levels were positively correlated with the expression of GRß in the CHB patients (r=0.419; P<0.05) and were significantly lower compared with those observed in the healthy controls (60.51 ± 23.73, vs. 100.00 ± 40.75; P<0.001). Compared with the healthy controls, significant differences were observed in the mRNA expression of GRα in the CHB patients when stratified according to the HBeAg, pre­S1Ag and HBV viral load status (P<0.05), but not in the pre­S1Ag­positive patients. These data demonstrated that the mRNA expression profile of GRα differed between the CHB patients and the healthy controls. In addition, the HBV serological and virological markers were not associated with the mRNA levels of the GR isoforms in the CHB patients.

[Effects of different treatment methods of housefly pupae for the reproduction of Pachycrepoideus vindemmiae Rondani].

It is an important way to massively rear parasitoid wasps by using appropriate methods to treat the wasps' hosts and preserve them for a long duration. Pachycrepoideus vindemmiae Rondani is a pupal parasitoid of several dipteral pests, being of significance for the biological control of the pests. In this paper, housefly pupae were frozen at -20 degrees C, cold storage-preserved at 6 degrees C, and CO2-asphyxiated for 1-, 3-, and 30 days, respectively, and some pupae were heat-killed and cold storage-preserved for 30 days, aimed to approach the effects of these treatment methods on the reproduction of P. vindemmiae on the pupae. The results showed that P. vindemmiae could reproduce on the pupae treated with the above-mentioned methods, and the tibia length of the offspring had less difference with that on the fresh pupae. However, the reproduction of P. vindemmiae on the pupae treated with the above-mentioned methods except frozen decreased with the increasing preserving duration of the pupae. At the prerequisite of preserving for 30 days, frozen pupae had the highest P. vindemmiae offspring reproduction, suggesting that P. vindemmiae could be massively reared when the housefly pupae were treated by frozen and cold storage-preserved.

Defects in NKG2D ligand expression result in failed tolerance induction at the maternal-fetal interface: a possible cause for recurrent miscarriage.

Certain maternal immune responses against the fetus at the maternal-fetal interface may contribute to recurrent miscarriage (RM). Trophoblast cells involve in forming of maternal-fetal interface and interact with many immune cells, including NK cells. NK cells accumulate at the maternal-fetal interface and play a critical role during pregnancy. NKG2D ligands can activate NK cells through engaging with corresponding receptors. The 5'-end flanking regions of DNA sequence of some NKG2D ligands contain heat shock elements. It is very possible that oxidative stress, produced in pathological process of RM, induces abnormal NKG2D ligand expression in the trophoblast cells, which stimulate cytotoxicity of NK cells. Moreover, in normal pregnancy, soluble NKG2D ligands are secreted into sera by syncytiotrophoblast cells, which disturb NKG2D-mediated maternal anti-fetus immunity. Reduction of soluble NKG2D ligand levels in association with upregulation of NKG2D on immune cells may also contribute to pathogenesis of RM.