Poly[bis­(4,4′-bipyridine)(μ3-4,4′-dicarboxybiphenyl-3,3′-di­carboxyl­ato)iron(II)]

In the polymeric title complex, [Fe(C16H8O8)(C10H8N2)2]n, the iron(II) cation is coordinated by four O atoms from three different 4,4′-dicarboxybiphenyl-3,3′-di­carboxyl­ate ligands and two N atoms from two 4,4′-bipyridine ligands in a distorted octa­hedral geometry. The 4,4′-dicarboxybiphenyl-3,3′-di­carboxyl­ate ligands bridge adjacent cations, forming chains parallel to the c axis. The chains are further connected by inter­molecular O—H⋯N hydrogen bonds, forming two-dimensional supra­molecular layers parallel to (010)

Src-family protein tyrosine kinases: a promising target for treating chronic pain

Abstract Despite growing knowledge of the mechanisms of chronic pain, it remains a major challenge facing clinical practice. Src-family protein tyrosine kinases (SFKs), a group of non-receptor protein tyrosine kinases, have been implicated in neuronal development and synaptic plasticity. SFKs are critically central to various transmembrane receptors e.g. G-protein coupled receptor (GPCR), EphB receptor (EphBR), increased intracellular calcium, epidermal growth factor (EGF) and other growth factors that regulate the phosphorylation of N-methyl-D-aspartic acid receptor (NMDAR) 2B subunit, thus contributing to the development of chronic pain. SFKs have also been regarded as an important point of convergence of intracellular signaling components that regulate microglia functions and the immune response. Additionally, intrathecal administration of SFKs inhibitors significantly alleviates mechanical allodynia in different chronic pain models. Thus, here we reviewed the current evidence of the role of SFKs in the development of chronic pain caused by complete Freund's adjuvant (CFA) injection, peripheral nerve injury (PNI), streptozotocin (STZ) injection and bone metastasis. Moreover, the role of SFKs on the development of morphine tolerance has also been discussed. Management of SFKs therefore emerged as a potential therapeutic target for the treatment of chronic pain in terms of safety and efficacy. Key words Chronic pain; Src-family protein tyrosine kinases; N-methyl-D-aspartic acid receptor; Microglia

Seroprevalence and Genetic Characterization of Toxoplasma Gondii in Three Species of Pet Birds in China

Background Toxoplasmosis, caused by the protozoan parasite Toxoplasma gondii, is one of the most common zoonosis worldwide, affecting a wide range of warm-blooded mammals and birds worldwide. However, no information on T. gondii infection in pet birds in China is available. Therefore, this study was performed to determine the prevalence of T. gondii infection in pet birds in Gansu province, China. Methods A total of 687 blood samples were collected from pet birds (Carduelis spinus, Alauda gulgula, Cocothraustes migratorlus) in three representative administrative regions in Gansu province, northwest China between August 2011 and September 2012 T. gondii antibodies were determined using the modified agglutination test (MAT). Genomic DNA was extracted from the brain tissues of seropositive pet birds and T. gondii B1 gene was amplified using a semi-nested PCR.DNA samples giving positive B1 amplification were then genetically characterized using multi-locus PCR-RFLP. Results The overall T. gondii seroprevalence was 11.21% (77/687). C. spinus had the highest T. gondii seroprevalence (11.65%), followed by A. arvensis (11.39%) and C. migratorlus (5.26%), these differences were not statistically significant (P \u3e 0.05). Of 77 DNA samples, 8 were positive for the T. gondii B1 gene, four showed complete genotyping results. Only one genotype (the Type II variant: ToxoDB genotype #3) was identified. Conclusions The results of the present survey indicated the presence of T. gondii infection in pet birds in Gansu province, China. These data provide base-line information for the execution of control strategies against T. gondii infection in pet birds. To our knowledge, this is the first report documenting the occurrence of T. gondii prevalence and genotype in pet birds in China

The therapeutic potential of GABA in neuron-glia interactions of cancer-induced bone pain

Abstract: The development of effective therapeutics for cancer-induced bone pain (CIBP) remains a tremendous challenge owing to its unclear mechanisms. Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. Emerging studies have shown that disinhibition in the spinal cord dorsal horn may account for the development of chronic pain. However, the role of GABA in the development of CIBP remains elusive. In addition, accumulating evidence has shown that neuroglial cells in the peripheral nervous system, especially astrocytes and microglial cells, play an important role in the maintenance of CIBP. In this study, we investigated the expression of GABA and Gamma-aminobutyric acid transporter-1 (GAT-1), a transporter of GABA. Our results demonstrate that GABA was decreased in CIBP rats as expected. However, the expression of glutamic acid decarboxylase (GAD) 65 was up-regulated on day 21 after surgery, while the expression of glutamic acid decarboxylase (GAD) 67 remained unchanged after surgery. We also found that the expression of GAT-1 was up-regulated mainly in the astrocytes of the spinal cord. Moreover, we evaluated the analgesic effect of exogenous GABA and the GAT-1 inhibitor. Intrathecal administration of exogenous GABA and NO-711(a GAT-1 selective inhibitor) significantly reversed CIBP-induced mechanical allodynia in a dose-dependent manner. These results firstly show that neuron-glia interactions, especially on the GABAnergic pathway, contribute to the development of CIBP. In conclusion, exogenous GABA and GAT-1 inhibitor might be alternative therapeutic strategies for the treatment of CIBP. Keywords: Cancer-induced bone pain; Gamma-Aminobutyric acid; Glutamic acid decarboxylases; GABA transporters; NO-711; Astrocyt

4,4′-Bipyridinium bis(perchlorate)–4-aminobenzoic acid–4,4′-bipyridine–water (1/4/2/2)

In the structure of the title compound, C10H10N2 2+·2ClO4 −·4C7H7NO2·2C10H8N2·2H2O, the 4,4′-bipyridinium cation has a crystallographically imposed centre of symmetry. The cation is linked by N—H⋯N hydrogen bonds to adjacent 4,4′-bipyridine mol­ecules, which in turn inter­act via O—H⋯N hydrogen bonds with 4-amino­benzoic acid mol­ecules, forming chains running parallel to [30]. The chains are further connected into a three-dimensional network by N—H⋯O and O—H⋯O hydrogen-bonding inter­actions involving the perchlorate anion, the water mol­ecules and the 4-amino­benzoic acid mol­ecules. In addition, π–π stacking inter­actions with centroid–centroid distances ranging from 3.663 (6) to 3.695 (6) Å are present. The O atoms of the perchlorate anion are disordered over two sets of positions, with refined site occupancies of 0.724 (9) and 0.276 (9)

Poly[diaqua-μ-oxalato-μ-pyrazine-2-carbox­yl­ato-lanthanum(III)]

In the title complex, [La(C5H3N2O2)(C2O4)(H2O)2]n, the LaIII ion is coordinated by one N and three O atoms from two pyrazine-2-carboxylate ligands, by four O atoms from two oxalate ligands and by two O atoms of two water molecules, displaying a distorted bicapped square-anti­prismatic geometry. The carboxyl­ate groups of pyrazine-2-carboxyl­ate and oxalate ligands link the lanthanum metal centres, forming layers parallel to (10). The layers are further connected by inter­molecular O—H⋯O and N—H⋯O hydrogen-bonding inter­actions, forming a three-dimensional supra­molecular network

Cloning of a Novel Protein Interacting with BRS-3 and Its Effects in Wound Repair of Bronchial Epithelial Cells

Bombesin receptor subtype 3 (BRS-3), the orphan bombesin receptor, may play a role in the regulation of stress responses in lung and airway epithelia. Bombesin receptor activated protein (BRAP )is a novel protein we found in our previous study which interacts with BRS-3. This study was designed to observe the subcellular location and wound repair function of BRAP in human bronchial epithelial cells (HBECs). BRAP ORF was amplified by RT-PCR and ligated to pEGFP-C1 vector, and then the recombinant plasmid pEGFP-C1-BRAP was transfected into Hela cells. The location of BRAP protein was observed by laser confocal microscope, and the expression of it was analyzed by Western-blot. At the same time,we built the recombinant plasmid pcDNA3.1(+)-BRAP, transfected it into HBECs and observed its impact on cell cycle and wound repair of HBECs. The results showed that BRAP locates in membrane and cytoplasm and increases significantly in transfected cells. Flow cytometry results demonstrated that the recombinant plasmid increases S phase plus G2 phase of cell cycle by 25%. Microscopic video analysis system showed that the repair index of wounded HBECs increases by 20% through stable expression of BRAP. The present study demonstrated that BRAP locates in the membrane and cytoplasm, suggesting that this protein is a cytoplasm protein, which promotes cell cycle and wound repair of HBECs

Leukadherin-1-Mediated Activation of CD11b Inhibits LPS-Induced Pro-inflammatory Response in Macrophages and Protects Mice Against Endotoxic Shock by Blocking LPS-TLR4 Interaction

Dysregulation of macrophage has been demonstrated to contribute to aberrant immune responses and inflammatory diseases. CD11b, expressed on macrophages, plays a critical role in regulating pathogen recognition, phagocytosis, and cell survival. In the present study, we explored the effect of leukadherin-1 (LA1), an agonist of CD11b, on regulating LPS-induced pro-inflammatory response in macrophages and endotoxic shock. Intriguingly, we found that LA1 could significantly reduce mortalities of mice and alleviated pathological injury of liver and lung in endotoxic shock. In vivo studies showed that LA1-induced activation of CD11b significantly inhibited the LPS-induced pro-inflammatory response in macrophages of mice. Moreover, LA1-induced activation of CD11b significantly inhibited LPS/IFN-γ-induced pro-inflammatory response in macrophages by inhibiting MAPKs and NF-κB signaling pathways in vitro. Furthermore, the mice injected with LA1-treated BMDMs showed fewer pathological lesions than those injected with vehicle-treated BMDMs in endotoxic shock. In addition, we found that activation of TLR4 by LPS could endocytose CD11b and activation of CD11b by LA1 could endocytose TLR4 in vitro and in vivo, subsequently blocking the binding of LPS with TLR4. Based on these findings, we concluded that LA1-induced activation of CD11b negatively regulates LPS-induced pro-inflammatory response in macrophages and subsequently protects mice from endotoxin shock by partially blocking LPS-TLR4 interaction. Our study provides a new insight into the role of CD11b in the pathogenesis of inflammatory diseases

Oncometabolite 2-Hydroxyglutarate Is a Competitive Inhibitor of α-Ketoglutarate-Dependent Dioxygenases

IDH1 and IDH2 mutations occur frequently in gliomas and acute myeloid leukemia, leading to simultaneous loss and gain of activities in the production of α-ketoglutarate (α-KG) and 2-hydroxyglutarate (2-HG), respectively. Here we demonstrate that 2-HG is a competitive inhibitor of multiple α-KG-dependent dioxygenases, including histone demethylases and the TET family of 5-methlycytosine (5mC) hydroxylases. 2-HG occupies the same space as α-KG does in the active site of histone demethylases. Ectopic expression of tumor-derived IDH1 and IDH2 mutants inhibits histone demethylation and 5mC hydroxylation. In glioma, IDH1 mutations are associated with increased histone methylation and decreased 5-hydroxylmethylcytosine (5hmC). Hence, tumor-derived IDH1 and IDH2 mutations reduce α-KG and accumulate an α-KG antagonist, 2-HG, leading to genome-wide histone and DNA methylation alterations

Clopidogrel Plus Aspirin vs Aspirin Alone in Patients With Acute Mild to Moderate Stroke

Importance Dual antiplatelet therapy has been demonstrated to be superior to single antiplatelet in reducing recurrent stroke among patients with transient ischemic attack or minor stroke, but robust evidence for its effect in patients with mild to moderate ischemic stroke is lacking. Objective To evaluate whether dual antiplatelet therapy is superior to single antiplatelet among patients with mild to moderate ischemic stroke. Design, Setting, and Participants This was a multicenter, open-label, blinded end point, randomized clinical trial conducted at 66 hospitals in China from December 20, 2016, through August 9, 2022. The date of final follow-up was October 30, 2022. The analysis was reported on March 12, 2023. Of 3065 patients with ischemic stroke, 3000 patients with acute mild to moderate stroke within 48 hours of symptom onset were enrolled, after excluding 65 patients who did not meet eligibility criteria or had no randomization outcome. Interventions Within 48 hours after symptom onset, patients were randomly assigned to receive clopidogrel plus aspirin (n = 1541) or aspirin alone (n = 1459) in a 1:1 ratio. Main Outcomes and Measures The primary end point was early neurologic deterioration at 7 days, defined as an increase of 2 or more points in National Institutes of Health Stroke Scale (NIHSS) score, but not as a result of cerebral hemorrhage, compared with baseline. The superiority of clopidogrel plus aspirin to aspirin alone was assessed based on a modified intention-to-treat population, which included all randomized participants with at least 1 efficacy evaluation regardless of treatment allocation. Bleeding events were safety end points. Results Of the 3000 randomized patients, 1942 (64.6%) were men, the mean (SD) age was 65.9 (10.6) years, median (IQR) NIHSS score at admission was 5 (4-6), and 1830 (61.0%) had a stroke of undetermined cause. A total of 2915 patients were included in the modified intention-to-treat analysis. Early neurologic deterioration occurred in 72 of 1502 (4.8%) in the dual antiplatelet therapy group vs 95 of 1413 (6.7%) in the aspirin alone group (risk difference −1.9%; 95% CI, −3.6 to −0.2; P = .03). Similar bleeding events were found between 2 groups. Conclusions and Relevance Among Chinese patients with acute mild to moderate ischemic stroke, clopidogrel plus aspirin was superior to aspirin alone with regard to reducing early neurologic deterioration at 7 days with similar safety profile. These findings indicate that dual antiplatelet therapy may be a superior choice to aspirin alone in treating patients with acute mild to moderate stroke.Trial RegistrationClinicalTrials.gov Identifier: NCT0286900