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The transcription factor nuclear factor of kappa-light-chain-enhancer of activated B cells (NF-κB) is expressed in brown adipocytes, but its role remains largely unknown in the cells. This issue was addressed in current study by examining NF-κB in brown adipocytes in vitro and in vivo. NF-κB activity was increased by differentiation of brown adipocytes through elevation of p65 (RelA) expression. The transcriptional activity of NF-κB was induced by the cold stimulation with an elevation in S276 phosphorylation of p65 protein. Inactivation of NF-κB in brown adipocytes made the knockout mice [uncoupling protein 1 (Ucp1)–CreER–p65f/f, U-p65-KO] intolerant to the cold environment. The brown adipocytes exhibited an increase in apoptosis, a decrease in cristae density and uncoupling activity in the interscapular brown adipose tissue (iBAT) of p65-KO mice. The alterations became severer after cold exposure of the KO mice. The brown adipocytes of mice with NF-κB activation (p65 overexpression, p65-OE) exhibited a set of opposite alterations with a reduction in apoptosis, an increase in crista density and uncoupling activity. In mechanism, NF-κB inhibited expression of the adenine nucleotide translocase 2 (ANT2) in the control of apoptosis. Data suggest that NF-κB activity is increased in brown adipocytes by differentiation and cold stimulation to protect the cells from apoptosis through down-regulation of ANT2 expression.

IF1 (ATPIF1) is a nuclear DNA-encoded mitochondrial protein whose activity is inhibition of the F1Fo-ATP synthase to control ATP production. IF1 activity remains unknown in the regulation of GLP-1 activity. In this study, IF1 was examined in the diet-induced obese mice using the gene knockout (If1-KO) mice. The mice gained more body weight on a high fat diet without a change in food intake. Insulin tolerance was impaired, but the oral glucose tolerance was improved through an increase in GLP-1 secretion. The KO mice exhibited an improved intestine structure, mitochondrial superstructure, enhanced mitophagy, reduced apoptosis and decreased adenine nucleotide translocase 2 (ANT2) protein in the intestinal epithelial cells together with preserved gut microbiota. The data suggest that GLP-1 secretion was enhanced in the obese If1-KO mice to preserve glucose tolerance through a signaling pathway of ANT2/mitochondria/L-cells/GLP-1/insulin. IF1 is a potential mitochondrial target for induction of GLP-1 secretion in L-cells., Graphical abstract IF1 is a new target in the induction of GLP-1 secretion in the intestinal L-cells, which exhibit decreased apoptosis and increased mitophagy from ANT2 reduction in the If1-KO mice.Image 1

BACKGROUND The separation and purification of Porphyra haitanensis polysaccharide (PHP), and the determination of changes in molecular weight (Mw) and antioxidant capacity after in vitro digestion, were undertaken. RESULTS Analysis of two polysaccharide fractions (PHP0.5-1-UF and PHP1.0-1-UF) by various techniques showed that they were very pure sulfated polysaccharides without pigment or protein. PHP0.5-1-UF was filamentous or 'tape-like' sheets, whereas PHP1.0-1-UF had some filaments and large numbers of rounded aggregates. The Mw of PHP, PHP0.5-1-UF and PHP1.0-1-UF was 2.06 x 10(6) (+/- 2.02%), 6.68 x 10(6) (+/- 3.17%), and 1.14 x 10(6) (+/- 3.44%) (g mol(-1)), respectively. After in vitro digestion, the Mw of PHP, PHP0.5-1-UF, and PHP1.0-1-UF decreased. Their antioxidant capacities were markedly higher than before digestion, especially PHP0.5-1-UF and its digestion products, which might be related to the reductions in Mw. CONCLUSION These findings provide a greater understanding of the separation and purification of sulfated polysaccharides and the influence of digestion on biological activity. They also contribute to the practical application of sulfated polysaccharides in functional foods. (c) 2021 Society of Chemical Industry.

Bone tumors and tumor-like lesions require that comprehensive imaging contains soft tissues and bone structures. There are so many kinds of examinations that the patients with bone tumors and tumor-like lesions should be performed. The objective of this study was to demonstrate the clinical applicability of zero echo time (ZTE) magnetic resonance (MR) imaging in osseous bone tumor imaging and evaluate the image quality between computed tomography (CT) and ZTE imaging of bone tumors and tumor-like lesions. Thirty-six patients included 18 male patients (mean age: 35 ± 20 years) and 18 female patients (mean age: 42 ± 20 years) were recruited from a clinical cohort of patients undergoing MR and CT. We presented a novel scanning technique for MR scanners (750 W MR, GE Medical Systems) that could obtain ZTE images. ZTE images were acquired after standard-of-care MR imaging. Quality comparison of osseous findings was performed between ZTE and CT imaging using a five-point grading scale. The differences of image quality between ZTE and CT imaging were investigated using Mann–Whitney test. A significance level of P

Fructose 1,6-bisphosphatase (FBPase) has attracted substantial interest as a target associated with cancer and type 2 diabetes. Herein, we found that disulfiram and its derivatives can potently inhibit FBPase by covalently binding to a new C128 allosteric site distinct from the original C128 site in APO FBPase. Further identification of the allosteric inhibition mechanism reveals that the covalent binding of a fragment of 214 will result in the movement of C128 and the dissociation of helix H4 (123-128), which in turn allows S123 to more easily form new hydrogen bonds with K71 and D74 in helix H3 (69-72), thereby inhibiting FBPase activity. Notably, both disulfiram and 212 might moderately reduce blood glucose output in vivo. Therefore, our current findings not only identify a new covalent allosteric site of FBPase but also establish a structural foundation and provide a promising way for the design of covalent allosteric drugs for glucose reduction.

Background Metabolic inflammation plays an important role in the pathogenesis of atherosclerosis, type 2 diabetes, non-alcoholic fatty liver disease, and obesity. The above metabolic disorders often coexist and are closely related with systemic low-grade inflammation. Metabolic inflammatory syndrome (MIS), a cluster of these four metabolic disorders, is a novel concept that is thought to be a better predictor of coronary heart disease than metabolic syndrome. Adiponectin is an adipokine that increases insulin sensitivity and antioxidation as well as has an anti-atherosclerosis effect. It is unclear whether adiponectin is associated with MIS. The objective of this study was to assess whether circulating adiponectin can be used as an indicator for MIS in elderly adults. Methods A total of 136 elderly inpatients were divided into two groups: the MIS group and the non-MIS group. Characteristics, inflammatory markers, blood lipid metabolism, insulin resistance, and circulating adiponectin levels were assessed and compared between the two groups. Logistic regression analysis was used to explore the association between the associated factors and MIS. Results MIS patients were more likely to have a higher body mass index, have a higher fasting blood glucose level, be smokers, have fundus arteriosclerosis, have lower levels of adiponectin (4044.90 ± 3906.82 ng/mL vs 8503.89 ± 3523.89 ng/mL, p < 0.001), and have higher levels of inflammation (white blood cell and C-reactive protein) than non-MIS patients. Multiple factor analysis showed that lower adiponectin levels (OR = 22.937, p < 0.001) were independently associated with MIS. Adiponectin levels were lower in the vascular disease (2673.29 ± 1930.05 ng/mL vs 7194.38 ± 4615.83 ng/mL, p = 0.001), atherosclerosis (2374.14 [1496.41-4263.90] ng/mL vs 6037.48 [3865.61-10,373.60] ng/mL, p < 0.001), and type 2 diabetes (2391.73 [1386.41-4069.68] ng/mL vs 8916.03 [5801.14-12,724.45] ng/mL, p < 0.001) subgroups than in the non-MIS group. Conclusion Lower adiponectin levels in serum are associated with MIS. Low adiponectin may be used as a biomarker for atherosclerosis in patients with MIS.

In this paper, we use the inverse design method to design an optical interconnection system composed of wavelength demultiplexer and the same direction waveguide crossing on silicon-on-insulator (SOI) platform. A 2.4 μm × 3.6 μm wavelength demultiplexer with an input wavelength of 1.3–1.6 μm is designed. When the target wavelength of the device is 1.4 μm, the insertion loss of the output port is − 0.93 dB, and there is − 18.4 dB crosstalk, in TE0 mode. The insertion loss of the target wavelength of 1.6 μm in TE0 mode is − 0.88 dB, and the crosstalk is − 19.1 dB. Then, we designed a same direction waveguide crossing, the footprint is only 2.4 μm × 3.6 μm, the insertion loss of the wavelength 1.4 μm and 1.6 μm in TE0 mode is − 0.99 dB and − 1 dB, and the crosstalk is − 12.14 dB and − 14.34 dB, respectively. Finally, an optical interconnect structure composed of two devices is used, which can become the most basic component of the optical interconnect network. In TE0 mode, the insertion loss of the output wavelength of 1.4 μm at the output port is − 1.3 dB, and the crosstalk is − 29.36 dB. The insertion loss of the output wavelength of 1.6 μm is − 1.39 dB, and the crosstalk is − 38.99 dB.

Extracellular ADP, a derivative of ATP, interacts with the purinergic receptors in the cell membrane to regulate cellular activities. This signaling pathway remains unknown in the regulation of blood glucose in vivo. We investigated the acute activity of ADP in mice through a peritoneal injection. In the lean mice, in response to the ADP treatment, the blood glucose was elevated, and pyruvate tolerance was impaired. Hepatic gluconeogenesis was enhanced with elevated expression of glucogenic genes (G6pase and Pck1) in the liver. An elevation was observed in NADH, cAMP, AMP, GMP and citrate in the liver tissue in the targeted metabolomics assay. In the primary hepatocytes, ADP activated the cAMP/PKA/CREB signaling pathway, which was blocked by the antagonist (2211) of the ADP receptor P2Y13. In the circulation, gluconeogenic hormones including glucagon and corticosterone were elevated by ADP. Insulin and thyroid hormones (T3 and T4) were not altered in the blood. In the diet-induced obese (DIO) mice, NADH was elevated in the liver tissue to match the hepatic insulin resistance. Insulin resistance was intensified by ADP for further impairment in insulin tolerance. These data suggest that ADP induced the blood glucose through direct and indirect actions in liver. One of the potential pathways involves activation of the P2Y13/cAMP/PKA/CREB signaling pathway in hepatocytes and the indirect pathway may involve induction of the gluconeogenic hormones. NADH is a signal for gluconeogenesis in the liver of both DIO mice and lean mice.

Aims Neuromedin U (NMU), a highly conserved peptide, is implicated in energy homeostasis and is involved in regulating insulin secretion as a decretin hormone in animals. However, there have been no reports on the relationship between NMU and type 2 diabetes mellitus (T2DM). The aim of this study was to investigate circulating NMU concentrations in healthy subjects and T2DM patients and to evaluate the association between serum NMU levels and glucose-stimulated insulin secretion. Methods We used ELISA to analyze NMU concentrations in blood samples from newly diagnosed T2DM patients (n = 57) and age-, sex- and BMI-matched healthy control subjects (n = 50). Anthropometric parameters, oral glucose tolerance, glycosylated hemoglobin, blood lipids, insulin sensitivity, and insulin secretion were measured. Results No difference was observed in serum NMU levels between control subjects and newly diagnosed T2DM patients (p = 0.788). The oral glucose tolerance test (OGTT) results indicated that serum NMU concentrations did not change and did not correlate with insulin levels at fasting and 1 h, 2 h and 3 h after glucose load in both healthy controls and newly diagnosed T2DM patients. Conclusion Circulating NMU concentrations were similar in control subjects and newly diagnosed T2DM patients and were not associated with glucose-stimulated insulin secretion. Serum NMU is not a human decretin hormone and may not play a role in the pathogenesis of T2DM.

Glioma is a kind of malignant brain tumor which damages the central nervous system of adults. Recent years, the molecular mechanism involved in the initiation and progression of glioma has been widely reported. Long non-coding RNAs (lncRNAs) have been proved to be significant modulators in the biological processes of glioma. In this study, we found that lncRNA AGAP2-AS1 was differentially expressed in glioma tissue samples and cell lines. Kaplan-Meier method was used to analyze the correlation between AGAP2-AS1 expression and the overall survival of glioma patients. Higher expression of AGAP2-AS1 was correlated with the lower overall survival of glioma patients. Functionally, AGAP2-AS1 knockdown inhibited glioma cell proliferation and accelerated glioma cell apoptosis. Mechanistically, AGAP2-AS1 upregulated HDGF by sponging miR-15a/b-5p. The function of AGAP2-AS1-miR-15a/b-5p-HDGF axis was confirmed by performing rescue assays. Experimental results suggested that miR-15a/b-5p and HDGF involved in AGAP2-AS1-mediated glioma cell proliferation. Moreover, AGAP2-AS1 and HDGF were found to activate Wnt/β-catenin signaling pathway in glioma cell lines. In summary, this study demonstrated that AGAP2-AS1 promoted glioma cell proliferation by sponging miR-15a/b-5p to upregulate the expression of HDGF.

Aims Sodium butyrate (SB) is a major product of gut microbiota with signaling activity in the human body. It has become a dietary supplement in the treatment of intestinal disorders. However, the toxic effect of overdosed SB and treatment strategy remain unknown. The two issues are addressed in current study. Materials and methods SB (0.3–2.5 g/kg) was administrated through a single peritoneal injection in mice. The core body temperature and mitochondrial function in the brown adipose tissue and brain were monitored. Pharmacodynamics, targeted metabolomics, electron microscope, oxygen consumption rate and gene knockdown were employed to dissect the mechanism for the toxic effect. Key findings The temperature was reduced by SB (1.2–2.5 g/kg) in a dose-dependent manner in mice for 2–4 h. In the brain, the effect was associated with SB elevation and neurotransmitter reduction. Metabolites changes were seen in the glycolysis, TCA cycle and pentose phosphate pathways. Adenine nucleotide translocase (ANT) was activated by butyrate for proton transportation leading to a transient potential collapse through proton leak. The SB activity was attenuated by ANT inhibition from gene knockdown or pharmacological blocker. ROS was elevated by SB for the increased ANT activity in proton leak in Neuro-2a. Significance Excessive SB generated an immediate and reversible toxic effect for inhibition of body temperature through transient mitochondrial dysfunction in the brain. The mechanism was quick activation of ANT proteins for potential collapse in mitochondria. ROS may be a factor in the ANT activation by SB.

IF1 (ATPIF1) is a nuclear DNA-encoded protein with an activity in the inhibition of catalytic activity of F1Fo-ATP synthase (ATPase), an enzyme for ATP synthesis in mitochondria. A role of IF1 remains unknown in the metabolic disorder in obesity. In this study, IF1 was examined in the diet-induced obese (DIO) mice and a decrease in IF1 protein was observed in several tissues including the skeletal muscle, liver and intestine in the absence of mRNA alteration. Significance of the reduction was investigated in the IF1-KO mice, in which insulin sensitivity was improved in the absence of body weight alteration on Chow diet. On a high fat diet (HFD), the IF1-KO mice gain more body weight as a result of enhanced fat tissue growth. The energy expenditure and locomotion activity were decreased in the KO mice without an alteration in food intake. The increase in insulin sensitivity remained in the obese KO mice. The colon tissue exhibited a resistance to the HFD-induced atrophy with less cell apoptosis and more secretion of GLP-1. Mitochondria exhibited an enhanced ATP production and maximal oxygen consumption without an alteration in the respiratory chain proteins. However, the ATP level was reduced in the fasting condition in the muscle as well as the liver. Mitophagy was enhanced with elevated accumulation of PINK1 and Parkin proteins in the mitochondria. The protein abundance of ADP/ATP translocase 2 (ANT2) was decreased in the inner membrane of mitochondria to account for the reduced apoptosis and enhanced mitophagy. The data suggest that the IF1 reduction in obesity leads to reprogramming of mitochondrial metabolism in a compensatory response to maintain the insulin sensitivity through down-regulation of ANT2 protein.

Chronic endometritis (CE) is an unusual inflammatory condition characterized by endometrial plasmacyte infiltration. It has a high prevalence in women with reproductive failure. Because of its characteristic localization patterns and molecular functions, syndecan-1 has been identified as a biomarker of plasmacyte, and syndecan-1 immunohistochemistry (IHC) becomes the most dependable diagnostic method for CE. In this review, we discuss the association between CE and reproductive failure, the clinicopathological characterization of CE, the function and expression of syndecan-1, the progress of syndecan-1 IHC in the diagnosis of CE, and the prediction of reproductive outcome.

Mitochondrial 2-enoyl-acyl-carrier protein reductase (MECR) is an enzyme in the mitochondrial fatty acid synthase (mtFAS) pathway. MECR activity remains unknown in the mechanism of insulin resistance in the pathogenesis of type 2 diabetes. In the present study, MECR activity was investigated in diet-induced obese (DIO) mice. Mecr mRNA was induced by insulin in cell culture, and was elevated in the liver of DIO mice in the presence hyperinsulinemia. However, MECR protein was decreased in the liver of DIO mice, and the reduction was blocked by treatment of the DIO mice with berberine (BBR). The mechanism of MECR protein regulation was investigated with a focus on ATP. The protein was decreased in the cell lysate and DIO liver by an increase in ATP levels. The ATP protein reduction was blocked in the liver of BBR-treated mice by suppression of ATP elevation. The MECR protein reduction was associated with insulin resistance and the protein restoration was associated with improvement of insulin sensitivity by BBR in the DIO mice. The data suggest that MECR protein is regulated in hepatocytes by ATP in association with insulin resistance. The study provides evidence for a relationship between MECR protein and insulin resistance.

Induction of apoptosis is a strategy in the treatment of glioma, a malignant tumor with the highest prevalence in the brain. Sodium butyrate (NaB) induces apoptosis in glioma cells at pharmacological dosages (>2.5 mM), but the mechanism remains largely unknown beyond the mitochondrial potential drop. In this study, NaB was found to open the mitochondrial permeability transient pore (MPTP) to induce a proton leak in the mechanism of apoptosis. The MPTP opening led to collapse of mitochondrial potential and suppression of ATP production in the NaB-treated cells. Proton leak was increased in the mitochondria under the coupling and uncoupling conditions from the MPTP opening. The proton leak was associated with an elevation in the protein abundance of adenine nucleotide translocator 2 (ANT2) and was blocked by an ANT-specific inhibitor of bongkrekic acid (BA). These data suggest that the proton leak is induced by NaB for the mitochondrial potential drop in the induction of apoptosis. The mechanism may be related to activation of ANT2 in the MPTP complex.

Translocation of the dense nucleus along a gravity vector initiates mechanical remodeling of a cell, but the underlying mechanisms of cytoskeletal network and focal adhesion complex (FAC) reorganization in a mammalian cell remain unclear. We quantified the remodeling of an MC3T3-E1 cell placed in upward-, downward-, or edge-on-orientated substrate. Nucleus longitudinal translocation presents a high value in downward orientation at 24 h or in edge-on orientation at 72 h, which is consistent with orientation-dependent distribution of perinuclear actin stress fibers and vimentin cords. Redistribution of total FAC area and fractionized super mature adhesion number coordinates this dependence at short duration. This orientation-dependent remodeling is associated with nucleus flattering and lamin A/C phosphorylation. Actin depolymerization or Rho-associated protein kinase signaling inhibition abolishes the orientation dependence of nucleus translocation, whereas tubulin polymerization inhibition or vimentin disruption reserves the dependence. A biomechanical model is therefore proposed for integrating the mechanosensing of nucleus translocation with cytoskeletal remodeling and FAC reorganization induced by a gravity vector.-Zhang, C., Zhou, L., Zhang, F., Lü, D., Li, N., Zheng, L., Xu, Y., Li, Z., Sun, S., Long, M. Mechanical remodeling of normally sized mammalian cells under a gravity vector.

It is well known that the warming process is a critical step in cell cryopreservation, affecting the survival rate of the cryopreserved cells. However, there is a lack of understanding and optimization of the warming process for the cryopreserved human peripheral blood mononuclear cells (PBMCs) that are greatly needed for the cellular/immune therapies worldwide. In this study, the effect of the warming process on cryosurvival of the PBMCs was investigated, resulting in a recommendation of an optimal warming method. In the experiments, all PBMC samples were cooled by a fixed slow cooling process and stored in a liquid nitrogen tank. The frozen samples were then warmed in water baths with stirring at various temperatures, 37°C, 42°C, and 65°C, respectively. After thawing, PBMC's viability as well as phenotypic and functional analyses were performed and evaluated. It was shown that a relatively rapid warming process at 65°C in a water bath with stirring generated a significant improvement of cell viability, recovery, and functionality of the cryopreserved PBMCs. In addition, interferon-γ and interleukin-2 secretion were much higher in PBMCs thawed at 65°C than that in 42°C and 37°C, respectively. This study suggests that a rapid warming process at 65°C in a water bath should be used to replace the current conventional warming approach at 37°C.

Adhesion between two nucleated cells undergoes specific significances in immune responses and tumor metastasis since cellular adhesive molecules usually express on two apposed cell membranes. However, quantification of the interactions between two nucleated cells is still challenging in microvasculature. Here distinct cell systems were used, including three types of human cells (Jurkat cell or PMN vs. MDA-MB-231 cell) and two kinds of murine native cells (PMN vs. liver sinusoidal endothelial cell). Cell movement, compression to, and relaxation from the counterpart cell were quantified using an in-house developed gas-driven micropipette aspiration technique (GDMAT). This assay is robust to quantify this process since cell movement and contact inside a pipette are independent of the repeated test cycles. Measured approaching or retraction velocity follows well a normal distribution, which is independent on the cycle period. Contact area or duration also fits a Gaussian distribution and moreover contact duration is linearly correlated with the cycle period. Cell movement is positively related to gas flux but negatively associated to medium viscosity. Cell adhesion tends to reach an equilibrium state with increase of cycle period or contact duration. These results further the understanding in the dynamics of cell movement and contact in microvasculature.

Melatonin, an indolic compound, is a ubiquitous molecule with pleiotropic roles in plant. The effects of melatonin treatment on the development of gray mold, disease resistance signals and phenylpropanoid pathway in cherry tomato were investigated after the mature-green fruit were dipped in 0.1 mM melatonin for 60 min and subsequently stored at 22 ± 1 °C. The results showed that melatonin did not have antifungal activity against Botrytis cinerea in vitro, but significantly inhibited gray mold development caused by B. cinerea in tomato. The melatonin treatment induced a reactive oxygen species (ROS) burst, increased endogenous melatonin and salicylic acid (SA), and enhanced activities of chitinase (CHI) and β-1,3-glucanase (GLU) in tomato. Moreover, the treatment regulated the phenylpropanoid pathway by increasing activities of phenylalanine ammonia-lyase (PAL), 4-coumarate-coenzyme A ligase (4CL), and peroxidase (POD) accompanied by higher contents of total phenols, flavonoids and lignin in tomato. It was suggested that melatonin treatment would induce signaling molecules via the phenylpropanoid pathway that might contribute to enhancing resistance in tomato against fungi such as B. cinerea during postharvest storage.

Fructose-1, 6-bisphosphatase (FBPase) has been regarded as an attractive drug target to control blood glucose against Type 2 diabetes (T2D). In this study, by using the strategy of pharmacophore-based virtual screening, a novel scaffold inhibitor targeted the AMP allosteric site of human liver FBPase were screened, their inhibitory activities were further tested. The experimental results showed that compound H27 exhibited high inhibitory activities with the IC50 value of 5.3 μM. Therefore, compound H27 was chosen as the probe molecule, it's possible binding conformation targeted into FBPase was identified by using DOX2.0 strategy. The importance of key residues (T27, T31, K112 and R140) in allosteric site of FBPase for the binding inhibitors were validated by mutation experiments. The agreement between theory and experiment suggest that the interactional information of FBPase and inhibitors (H27) were reliable. On basis of these rational interactional information, the compound H29 was further designed to exhibit more potential FBPase inhibition (IC50 = 2.5 μM).

Dendrimer-entrapped gold nanoparticles (Au DENPs) can be formed using low-generation dendrimers pre-modified by polyethylene glycol (PEG). The formed PEGylated Au DENPs with desirable stability, cytocompatibility, and X-ray attenuation properties enable efficient computed tomography imaging of the heart and tumor model of mice.

Atherosclerosis is caused by chronic inflammation associated with the adhesion of neutrophils and endothelial cells (ECs) that is mediated by their respective cellular adhesive molecules to stiffened blood vessel walls. However, the stiffness dependence of calcium flux on neutrophils remains unclear yet. Here, the effect of substrate stiffness by ECs on neutrophils' calcium spike was quantified when the individual neutrophils that adhered to the human umbilical vascular endothelial cell (HUVEC) monolayer were pre-placed onto a stiffness-varied polyacrylamide substrate (5 or 34.88 kPa) or glass surface. Our data indicated that E-/P-selectins and intercellular adhesion molecule 1 (ICAM-1) on HUVECs and β2-integrins, P-selectin glycoprotein ligand 1 (PSGL-1), and CD44s on neutrophils were all involved in mediating neutrophil calcium spike in a stiffness-dependent manner, in which the increase in substrate stiffness enhanced the calcium intensity and the oscillation frequency (spike number). Such stiffness-dependent calcium response is associated with the induced selectin related to β2-integrin activation through the Syk/Src signaling pathway, and F-actin/myosin II are also involved in this. Moreover, tension-activated calcium ion channels displayed critical roles in initiating stiffness-dependent calcium spike. These results provide an insight into understanding how the stiffening of vascular walls could regulate the calcium flux of adhered neutrophils, and thus the immune responses in atherosclerosis.

The purpose of this study was to develop folic acid (FA)-modified iron oxide (Fe3O4) nanoparticles (NPs) for targeted magnetic resonance imaging (MRI) of H460 lung carcinoma cells. Water-dispersible Fe3O4 NPs synthesized via a mild reduction method were conjugated with FA to generate FA-targeted Fe3O4 NPs. The specificity of FA-targeted Fe3O4 NPs to bind FA receptor was investigated in vitro by cellular uptake and cell MRI and in vivo by MRI of H460 tumors. The formed NPs displayed good biocompatibility and ultrahigh r 2 relaxivity (440.01/mM/s). The targeting effect of the NPs to H460 cells was confirmed by in vitro cellular uptake and cell MRI. H460 tumors showed a significant reduction in T2 signal intensity at 0.85 h, which then recovered and returned to control at 2.35 h. The results indicate that the prepared FA-targeted Fe3O4 NPs have potential to be used as T2 negative contrast agents in targeted MRI.

Aims To find specific magnetic resonance imaging (MRI) features to differentiate metastatic ovarian tumors from primary epithelial ovarian cancers. Methods Eleven cases with metastatic ovarian tumors and 26 cases with primary malignant epithelial ovarian cancers were retrospectively studied. All features such as patient characteristics, MRI findings and biomarkers were evaluated. The differences including laterality, configuration, uniformity of locules, diffusion weighted imaging (DWI) signal of solid components and enhancement of solid portions between metastatic ovarian tumors and primary epithelial ovarian cancers were compared by Fisher’s exact test. Median age of patients, the maximum diameter of lesions and biomarkers were compared by the Mann-Whitney test. Results Patients with metastatic ovarian tumors were younger than patients with primary epithelial ovarian cancers in the median age (P = 0.015). Patients with bilateral tumors in metastatic ovarian tumors were more than those of primary epithelial ovarian cancers (P = 0.032). The maximum diameter of lesions in metastatic ovarian tumors was smaller than that of primary epithelial ovarian cancers (P = 0.005). The locules in metastatic ovarian tumors were more uniform than those of primary epithelial ovarian cancers (P = 0.024). The enhancement of solid portions in metastatic ovarian tumors showed more moderate than that of primary epithelial ovarian cancers (P = 0.037). There was no statistically significant difference between the two groups in configuration, DWI signal of solid components and ascites. Biomarkers such as CA125 and human epididymis protein 4 (HE4) in metastatic ovarian tumors showed less elevated than that of primary epithelial ovarian cancers. Conclusions Significant differences between metastatic ovarian tumors and primary epithelial ovarian cancers were found in the median age of patients, laterality, the maximum diameter of lesions, uniformity of locules, enhancement patterns of solid portions and biomarkers. Metastatic ovarian tumors usually presented in the younger patients, smaller-sized, more bilateral lesions, more uniform of locules, more moderate enhancement of solid portions, and less elevated levels of CA125 and HE4 than those of primary epithelial ovarian cancers.

Background: It is critical to follow up hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) in clinical practice. Computed tomography (CT) is used to assess lipiodol deposition, whereas it is difficult to assess hypovascular residual cancer masked by lipiodol. In contrast, magnetic resonance imaging (MRI) is superior to CT in showing residual cancer, but cannot display lipiodol deposition. Objectives: The aim of this study was to investigate the value of spectral CT imaging in both lipiodol deposition and residual cancer for HCC patients after TACE. Patients and Methods: Ten HCC patients after treated with TACE underwent Discovery CT750 HD and MRI750 3T examination. Receiver operating characteristic (ROC) curves of iodine-based material decomposition images, monochromatic images and conventional CT images were generated. Results: Consequently, 30 residual lesions were detected in MRI of 10 patients. They were found in iodine-based images and monochromatic images versus 29 in conventional CT images. The area under ROC curves for the lesion-to-normal parenchyma ratio (LNR) on arterial phase (AP) in iodine-based material decomposition images, monochromatic images and conventional CT images were 0.933, 0.833 and 0.817, respectively. Conclusion: The study data highlighted good value of iodine-based material decomposition images of spectral CT in assessment of both lipiodol deposition and residual cancer for follow-up of HCC patients previously treated with TACE.

Radix bupleuri, roots of Bupleurum species, is a widely used traditional Chinese medicine. Here, we compared the root transcriptomes of both Bupleurum chinense DC. and Bupleurum scorzonerifolium Willd. A total of 313 483 and 342 263 high quality expressed sequence tags were obtained, respectively. In addition, 17 117 (59.2%) and 19 416 (62.8%) unigenes for B. chinense and B. scorzonerifolium had homologous genes in the opposite dataset. For B. chinense, Kyoto Encyclopedia of Genes and Genomes database (KEGG) annotation identified carbohydrate metabolism, energy metabolism and amino acid metabolism as the three highest groups in the metabolism category. For B. scorzonerifolium, the lipid metabolism group had the most unigenes. Genes that may participate in the biosynthesis of terpenoid, triterpenoid, sterol, lignan and flavonoids were identified according to their annotations. (Tri)terpenoid-related genes were predominantly found in B. chinense. The expressions of certain genes were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in the roots of the two species. A total of 558 putative transcription factors (TFs) and 137 transcriptional regulators (TRs) among 1364 TFs and 327 TRs, and 610 TFs and 129 TRs among 1600 TFs and 323 TRs were specific for B. chinense and B. scorzonerifolium, respectively. Our transcriptome comparison reflects the different types and proportions of metabolites synthesized by the two species. The data, especially, those genes involved in the biosynthesis of particular types of metabolites, will provide the basis for further investigations of the secondary metabolite repertoire of the two Bupleurum species, as well as other species from the genus of Bupleurum.

Background aims Adipose-derived stem cells (ADSCs) have shown great promise in the regenerative repair of injured peripheral nerves. Magnetic resonance imaging (MRI) has provided attractive advantages in tracking superparamagnetic iron oxide nanoparticle (SPION)-labeled cells and evaluating their fate after cell transplantation. This study investigated the feasibility of the use of MRI to noninvasively track ADSCs repair of peripheral nerve injury in vivo . Methods Green fluorescent protein (GFP)-expressing ADSCs were isolated, expanded, differentiated into an SC-like phenotype (GFP-dADSCs) at early passages and subsequently labeled with SPIONs. The morphological and functional properties of the GFP-dADSCs were assessed through the use of immunohistochemistry. The intracellular stability, proliferation and viability of the labeled cells were evaluated in vitro . Through the use of a microsurgical procedure, the labeled cells were then seeded into sciatic nerve conduits in C57/BL6 mice to repair a 1-cm sciatic nerve gap. A clinical 3-T MRI was performed to investigate the GFP-dADSCs in vitro and the transplanted GFP-dADSCs inside the sciatic nerve conduits in vivo . Results The GFP-dADSCs were efficiently labeled with SPIONs, without affecting their viability and proliferation. The labeled cells implanted into the mice sciatic nerve conduit exhibited a significant increase in axonal regeneration compared with the empty conduit and could be detected by MRI. Fluorescent microscopic examination, histological analysis and immunohistochemistry confirmed the axon regeneration and MRI results. Conclusions These data will elucidate the neuroplasticity of ADSCs and provide a new protocol for in vivo tracking of stem cells that are seeded to repair injured peripheral nerves.

A composicao e atividade antimicrobiana dos oleos essenciais obtidos de madeira de agar originaria de Aquilaria sinensis (Lour.) Gilg induzido por agente biologico da madeira de agar, Lasiodiplodia theobromae (F), foram caracterizadas e comparadas com madeira de agar selvagem (W) e arvores saudaveis nao inoculadas (H) como controles positivo e negativo, respectivamente. A composicao quimica de F foi investigada usando cromatografia gasosa-espectrometria de massas (GC-MS). O oleo essencial de F mostrou uma composicao similar de W, sendo rico em sesquiterpenos e constituintes aromaticos. No entanto, o oleo essencial de H era abundante em alcanos. Os oleos essenciais de F e W mostraram ser inibidores mais potentes de L. theobromae, Fusarium oxysporum, e Candida albicans do que o oleo essencial de H. Nossas descobertas demonstram pela primeira vez que o oleo essencial obtido da madeira de agar originado de A. sinensis induzido por L. theobromae teve uma alta similaridade com o oleo essencial da madeira de agar selvagem, tanto em composicao quimica como em atividade antimicrobiana. Alem disso, a estrategia de madeira de agar induzida por fungos pode ser potencialmente aplicada em madeira de agar e producao de oleo essencial em arvores do genero Aquilaria. The composition and antimicrobial activity of essential oils obtained from agarwood originating from Aquilaria sinensis (Lour.) Gilg induced by a biological agent of agarwood, Lasiodiplodia theobromae (F), were characterized and compared to those from wild agarwood (W) and uninoculated healthy trees (H) as positive and negative control, respectively. The chemical composition of F was investigated using gas chromatography-mass spectrometry (GC-MS). The essential oil of F showed a similar composition to that of W, being rich in sesquiterpenes and aromatic constituents. However, the essential oil of H was abundant in alkanes. Essential oils of F and W were more potent inhibitors of L. theobromae, Fusarium oxysporum, and Candida albicans than the essential oil of H. Our findings demonstrate for the first time that the essential oil obtained from the agarwood originating from A. sinensis induced by L. theobromae had a high similarity to that of the essential oil of wild agarwood, both in chemical composition and in antimicrobial activity. Furthermore, the strategy of agarwood induced by fungi could be potentially applied in agarwood and essential oil production in Aquilaria trees.