Two-photon excitable boron complex based on tridentate imidazo[1,5-a]pyridine ligand for heavy-atom-free mitochondria-targeted photodynamic therapy

We have synthesized a cyan fluorescent boron complex based on a tridentate imidazo[1,5-a]pyridine ligand. The boron complex was found to have potential applications as not only a chiroptical material but also a heavy-atom-free mitochondria-targeted photosensitizer for cancer treatment

The circadian clock is disrupted in mice with adenine-induced tubulointerstitial nephropathy.

Chronic Kidney Disease (CKD) is increasing in incidence and has become a worldwide health problem. Sleep disorders are prevalent in patients with CKD raising the possibility that these patients have a disorganized circadian timing system. Here, we examined the effect of adenine-induced tubulointerstitial nephropathy on the circadian system in mice. Compared to controls, adenine-treated mice showed serum biochemistry evidence of CKD as well as increased kidney expression of inflammation and fibrosis markers. Mice with CKD exhibited fragmented sleep behavior and locomotor activity, with lower degrees of cage activity compared to mice without CKD. On a molecular level, mice with CKD exhibited low amplitude rhythms in their central circadian clock as measured by bioluminescence in slices of the suprachiasmatic nucleus of PERIOD 2::LUCIFERASE mice. Whole animal imaging indicated that adenine treated mice also exhibited dampened oscillations in intact kidney, liver, and submandibular gland. Consistently, dampened circadian oscillations were observed in several circadian clock genes and clock-controlled genes in the kidney of the mice with CKD. Finally, mice with a genetically disrupted circadian clock (Clock mutants) were treated with adenine and compared to wild type control mice. The treatment evoked worse kidney damage as indicated by higher deposition of gelatinases (matrix metalloproteinase-2 and 9) and adenine metabolites in the kidney. Adenine also caused non-dipping hypertension and lower heart rate. Thus, our data indicate that central and peripheral circadian clocks are disrupted in the adenine-treated mice, and suggest that the disruption of the circadian clock accelerates CKD progression

Cerebral infarct with idiopathic cervical internal carotid artery vasospasm: A case report and literature review

Intracranial vasospasm that results from subarachnoid hemorrhage mostly leads to cerebral infarct. On the other hand, cervical internal carotid artery (CICA) vasospasm is caused by various factors such as cervical surgery, taking ergotamine, or is of unknown origin. We report here a rare case of cerebral infarct due to repeated idiopathic bilateral CICA vasospasm, and present a review of the literature. A 38-year-old man, who had a medical history of cerebral infarcts at the ages of 27 and 35, was admitted complaining of disturbance of consciousness and aphasia. MRI and MRA revealed cerebral infarct of the left middle cerebral artery (MCA) area due to occlusion of the left cervical internal carotid artery. Cerebral angiography at 9 days after onset, we demonstrated that the right CICA was occluded, whereas the left CICA was recanalized. On the 32nd day after onset, MRA showed the bilateral CICA to be recanalized. Idiopathic CICA vasospasm should be considered as a cause of juvenile-onset cerebral infarct. Regular follow-up is therefore needed because idiopathic CICA vasospasm is prone to recurrence. Keywords: Cervical internal carotid artery vasospasm, Juvenile-onset cerebral infarct, Internal carotid artery dissection, Fibromuscular dysplasia, Rho kinase inhibito

Biophysical characterization and single-chain Fv construction of a neutralizing antibody to measles virus

The measles virus (MV) is a major cause of childhood morbidity and mortality worldwide. We previously established a mouse monoclonal antibody, 2F4, which shows high neutralizing titers against eight different genotypes of MV. However, the molecular basis for the neutralizing activity of the 2F4 antibody remains incompletely understood. Here, we have evaluated the binding characteristics of a Fab fragment of the 2F4 antibody. Using the MV infectious assay, we demonstrated that 2F4 Fab inhibits viral entry via either of two cellular receptors, SLAM and Nectin4. Surface plasmon resonance (SPR) analysis of recombinant proteins indicated that 2F4 Fab interacts with MV hemagglutinin (MV-H) with a K-D value at the nm level. Furthermore, we designed a single-chain Fv fragment of 2F4 antibody as another potential biopharmaceutical to target measles. The stable 2F4 scFv was successfully prepared by the refolding method and shown to interact with MV-H at the mu m level. Like 2F4 Fab, scFv inhibited receptor binding and viral entry. This indicates that 2F4 mAb uses the receptor-binding site and/or a neighboring region as an epitope with high affinity. These results provide insight into the neutralizing activity and potential therapeutic use of antibody fragments for MV infection