catena-Poly[[bis­[2-(2-pyrid­yl)-1-H-imidazole-κ2 N 2,N 3]cadmium]-μ-benzene-1,3-dicarboxyl­ato-κ2 O 1:O 3]

In the title coordinaltion polymer, [Cd(C8H4O4)(C8H7N3)2]n, the CdII atom, lying on a twofold rotation axis, is six-coordinated by two carboxyl­ate O atoms from two benzene-1,3-dicarboxyl­ate (m-BDC) ligands and four N atoms from two chelating 2-(2-pyrid­yl)imidazole mol­ecules, forming a slightly distorted octa­hedral geometry. The m-BDC ligand is located over a twofold rotation axis. The CdII atoms are bridged by the m-BDC ligands, leading to a wave-shaped chain structure along [010]. N—H⋯O hydrogen bonds connect the chains

Expression of CD147 on monocytes/macrophages in rheumatoid arthritis: its potential role in monocyte accumulation and matrix metalloproteinase production

Monocytes/macrophages play an important role in rheumatoid arthritis (RA) pathogenesis. They can activate fibroblasts through many molecules, including IL-1 and tumor necrosis factor-alpha, but there have been very few reports on the role of CD147 in RA. In our study, the results of flow cytometry reveal that the mean fluorescence intensity (MFI) of CD147 expression on CD14+ monocytes of peripheral blood from RA patients was higher than that in normal control and ankylosing spondylitis (AS) patients. The MFI of CD147 expression on the CD14+ monocytes in RA synovial fluid was higher than that in RA peripheral blood. Immunohistochemical staining shows that CD147 expression in RA synovium correlated with matrix metalloproteinase (MMP)-1 expression. A double immunofluorescent assay shows that CD147 was expressed on CD68+ cells in RA synovium. The potential role of CD147 in cyclophilin A (CyPA)-mediated cell migration was studied using a chemotaxis assay in vitro and it was found that the addition of anti-CD147 antibody or a CD147 antagonistic peptide significantly decreased the chemotactic index of the mononuclear cells. The role of CD147 in MMP production and cell invasion in vitro were studied through the co-culture of human CD14+ monocytes or monocytic line THP-1 cells and human fibroblasts, as well as by gel zymography and an invasion assay. Significantly elevated release and activation of MMP-9 and/or MMP-2 were seen in the co-culture of human monocytes/THP-1 cells and fibroblasts compared with cultures of the cells alone. An increased number of cells invading through the filters in the invasion assays was also observed in the co-cultured cells. The addition of CD147 antagonistic peptide had some inhibitory effect, not only on MMP production but also on cell invasion in the co-culture. Our study demonstrates that the increased expression of CD147 on monocytes/macrophages in RA may be responsible for elevated MMP secretion, cell invasion and CyPA-mediated cell migration into the joints, all of which may contribute to the cartilage and bone destruction of RA. These findings, together with a better understanding of CD147, CyPA and RA, will help in the development of innovative therapeutic interventions for RA

Five Classification of Mammography Images Based on Deep Cooperation Convolutional Neural Network

Mammography is currently the preferred imaging method for breast cancer screening. Masses and calcification are the main positive signs of mammography. Due to the variable appearance of masses and calcification, a significant number of breast cancer cases are missed or misdiagnosed if it is only depended on the radiologists’ subjective judgement. At present, most of the studies are based on the classical Convolutional Neural Networks (CNN), which uses the transfer learning to classify the benign and malignant masses in the mammography images. However, the CNN is designed for natural images which are substantially different from medical images. Therefore, we propose a Deep Cooperation CNN (DCCNN) to classify mammography images of a data set into five categories including benign calcification, benign mass, malignant calcification, malignant mass and normal breast. The data set consists of 695 normal cases from DDSM, 753 calcification cases and 891 mass cases from CBIS-DDSM. Finally, DCCNN achieves 91% accuracy and 0.98 AUC on the test set, whose performance is superior to VGG16, GoogLeNet and InceptionV3 models. Therefore, DCCNN can aid radiologists to make more accurate judgments, greatly reducing the rate of missed and misdiagnosis

Effects and mechanism of anti-VEGF assisted PPV in the treatment of proliferative retinopathy

AIM: To investigate the effects and mechanism of anti-vascular endothelial growth factor(VEGF)assisted pars plana vitrectomy(PPV)in the treatment of proliferative diabetic retinopathy(PDR).METHODS: A total of 92 patients(92 eyes)with PDR treated by PPV were divided into the simple PPV group(41 patients with 41 affected eyes)and the combined treatment group(51 patients with 51 affected eyes)according to whether the patient underwent intravitreal injection of Ranibizumab(IVR). The combined treatment group was treated with IVR at 5-7d before PPV. The surgical time, times of electrocoagulation, silicone oil filling rate, the incidence of postoperative complications, LogMAR BCVA of affected eyes, levels of VEGF and pigment epithelium derived factor(PEDF)in aqueous humor and vitreous body were compared between the two groups. RESULTS: The surgical time was shorter, the times of electrocoagulation was less, the silicone oil filling rate and the incidence rates of iatrogenic retinal hole and vitreous body hematocele were lower in the combined treatment group than in the simple PPV group(PPPCONCLUSION: IVR combined with PPV can reduce the perioperative levels of VEGF and PEDF, reduce the times of electrocoagulation and the incidence of iatrogenic retinal hole and vitreous body hematocele, and improve the visual acuity of patients with PDR

MicroRNA-21 inhibitor sensitizes human glioblastoma cells U251 (PTEN-mutant) and LN229 (PTEN-wild type) to taxol

<p>Abstract</p> <p>Background</p> <p>Substantial data indicate that the oncogene microRNA 21 (miR-21) is significantly elevated in glioblastoma multiforme (GBM) and regulates multiple genes associated with cancer cell proliferation, apoptosis, and invasiveness. Thus, miR-21 can theoretically become a target to enhance the chemotherapeutic effect in cancer therapy. So far, the effect of downregulating miR-21 to enhance the chemotherapeutic effect to taxol has not been studied in human GBM.</p> <p>Methods</p> <p>Human glioblastoma U251 (PTEN-mutant) and LN229 (PTEN wild-type) cells were treated with taxol and the miR-21 inhibitor (in a poly (amidoamine) (PAMAM) dendrimer), alone or in combination. The 50% inhibitory concentration and cell viability were determined by the MTT assay. The mechanism between the miR-21 inhibitor and the anticancer drug taxol was analyzed using the Zheng-Jun Jin method. Annexin V/PI staining was performed, and apoptosis and the cell cycle were evaluated by flow cytometry analysis. Expression of miR-21 was investigated by RT-PCR, and western blotting was performed to evaluate malignancy related protein alteration.</p> <p>Results</p> <p>IC(50) values were dramatically decreased in cells treated with miR-21 inhibitor combine with taxol, to a greater extent than those treated with taxol alone. Furthermore, the miR-21 inhibitor significantly enhanced apoptosis in both U251 cells and LN229 cells, and cell invasiveness was obviously weakened. Interestingly, the above data suggested that in both the PTEN mutant and the wild-type GBM cells, miR-21 blockage increased the chemosensitivity to taxol. It is worth noting that the miR-21 inhibitor additively interacted with taxol on U251cells and synergistically on LN229 cells. Thus, the miR-21 inhibitor might interrupt the activity of EGFR pathways, independently of PTEN status. Meanwhile, the expression of STAT3 and p-STAT3 decreased to relatively low levels after miR-21 inhibitor and taxol treatment. The data strongly suggested that a regulatory loop between miR-21 and STAT3 might provide an insight into the mechanism of modulating EGFR/STAT3 signaling.</p> <p>Conclusions</p> <p>Taken together, the miR-21 inhibitor could enhance the chemo-sensitivity of human glioblastoma cells to taxol. A combination of miR-21 inhibitor and taxol could be an effective therapeutic strategy for controlling the growth of GBM by inhibiting STAT3 expression and phosphorylation.</p

A novel strategy for rapid identification of the fruits of Illicium verum and Illicium anisatum using electronic nose and tongue technology

Purpose: To develop an effective and rapid strategy for the identification of fruits of I. verum and I. anisatum based on their odor and taste.Methods: Electronic nose (E-nose) and electronic tongue (E-tongue) technology was used to identify the fruits of I. verum (FIV) and I. anisatum (FIA). Samples of FIA, FIV, and FIA : FIV mixtures in different proportions (1 : 3, 1 : 1, and 3 : 1) were prepared to evaluate the identification abilities of E-nose and Etongue methods. Samples were powdered and sifted through a standard sieve (aperture size 355 ± 13 μm) for E-nose analysis. Each sample was refluxed with water for 1 h before E-tongue analysis. The acquired data were analyzed by principal component analysis (PCA) and discriminant factor analysis (DFA).Results: Based on the signals acquired by E-nose and E-tongue analyses, a total of 90 data points each were used for PCA. The three principal component values for E-nose analysis were PC1 = 93.89 %, PC2 = 6.08 %, and PC3 = 0.03 %, and those for E-tongue analysis were PC1 = 98.72 %, PC2 = 0.68 %, and PC3 = 0.57 %. The sample data were significantly divided into two groups representing FIV and FIA. Furthermore, E-nose and E-tongue assessments combined with PCA and DFA analyses effectively identified FIV, FIA and their mixtures.Conclusion: The use of E-nose and E-tongue technology is an effective and rapid strategy to identify the fruits of I. verum and I. anisatum and their mixtures. This strategy may also offer an effective method for detection of adulterants.Keywords: Illicium verum, Illicium anisatum, Discrimination, Electronic nose, Electronic tongue, Safety, Principal component analysis, Discriminant factor analysi

Acute Stress Facilitates LTD Induction at Glutamatergic Synapses in the Hippocampal CA1 Region by Activating μ-Opioid Receptors on GABAergic Neurons

Acute stress impairs recall memory through the facilitation of long-term depression (LTD) of hippocampal synaptic transmission. The endogenous opioid system (EOS) plays essential roles in stress-related emotional and physiological responses. Specifically, behavioral studies have shown that the impairment of memory retrieval induced by stressful events involves the activation of opioid receptors. However, it is unclear whether signaling mediated by μ-opioid receptors (μRs), one of the three major opioid receptors, participates in acute stress-related hippocampal LTD facilitation. Here, we examined the effects of a single elevated platform (EP) stress exposure on excitatory synaptic transmission and plasticity at the Schaffer collateral-commissural (SC) to CA1 synapses by recording electrically evoked field excitatory postsynaptic potentials and population spikes of hippocampal pyramidal neurons in anesthetized adult mice. EP stress exposure attenuated GABAergic feedforward and feedback inhibition of CA1 pyramidal neurons and facilitated low-frequency stimulation (LFS)-induced long-term depression (LTD) at SC-CA1 glutamatergic synapses. These effects were reproduced by exogenously activating μRs in unstressed mice. The specific deletion of μRs on GABAergic neurons (μRGABA) not only prevented the EP stress-induced memory impairment but also reversed the EP stress-induced attenuation of GABAergic inhibition and facilitation of LFS-LTD. Our results suggest that acute stress endogenously activates μRGABA to attenuate hippocampal GABAergic signaling, thereby facilitating LTD induction at excitatory synapses and eliciting memory impairments

Immune Cells in the BBB Disruption After Acute Ischemic Stroke: Targets for Immune Therapy?

Blood-Brain Barrier (BBB) disruption is an important pathophysiological process of acute ischemic stroke (AIS), resulting in devastating malignant brain edema and hemorrhagic transformation. The rapid activation of immune cells plays a critical role in BBB disruption after ischemic stroke. Infiltrating blood-borne immune cells (neutrophils, monocytes, and T lymphocytes) increase BBB permeability, as they cause microvascular disorder and secrete inflammation-associated molecules. In contrast, they promote BBB repair and angiogenesis in the latter phase of ischemic stroke. The profound immunological effects of cerebral immune cells (microglia, astrocytes, and pericytes) on BBB disruption have been underestimated in ischemic stroke. Post-stroke microglia and astrocytes can adopt both an M1/A1 or M2/A2 phenotype, which influence BBB integrity differently. However, whether pericytes acquire microglia phenotype and exert immunological effects on the BBB remains controversial. Thus, better understanding the inflammatory mechanism underlying BBB disruption can lead to the identification of more promising biological targets to develop treatments that minimize the onset of life-threatening complications and to improve existing treatments in patients. However, early attempts to inhibit the infiltration of circulating immune cells into the brain by blocking adhesion molecules, that were successful in experimental stroke failed in clinical trials. Therefore, new immunoregulatory therapeutic strategies for acute ischemic stroke are desperately warranted. Herein, we highlight the role of circulating and cerebral immune cells in BBB disruption and the crosstalk between them following acute ischemic stroke. Using a robust theoretical background, we discuss potential and effective immunotherapeutic targets to regulate BBB permeability after acute ischemic stroke

Effects of tumor metabolic microenvironment on regulatory T cells

Recent studies have shown that on one hand, tumors need to obtain a sufficient energy supply, and on the other hand they must evade the body’s immune surveillance. Because of their metabolic reprogramming characteristics, tumors can modify the physicochemical properties of the microenvironment, which in turn affects the biological characteristics of the cells infiltrating them. Regulatory T cells (Tregs) are a subset of T cells that regulate immune responses in the body. They exist in large quantities in the tumor microenvironment and exert immunosuppressive effects. The main effect of tumor microenvironment on Tregs is to promote their differentiation, proliferation, secretion of immunosuppressive factors, and chemotactic recruitment to play a role in immunosuppression in tumor tissues. This review focuses on cell metabolism reprogramming and the most significant features of the tumor microenvironment relative to the functional effects on Tregs, highlighting our understanding of the mechanisms of tumor immune evasion and providing new directions for tumor immunotherapy