Current status of thiopurine analogues in the treatment in Crohn's disease

In the last decades,with the development of biological therapy,the treatment paradigms in patients with Crohn＇s disease have continuously evolved.Several studies focusing on the optimal use of both traditional immunosuppressants and biological therapy have been published,investigating conventional,accelerated stepup and top-down approaches.In addition,much emphasis has been placed in recent years on the de-termination of important predictive factors that could enable early patient stratification,which would lead to a tailored management strategy.In this review,the authors try to highlight new evidence on the optimal timing,benefits,and risks of immunosupressants alone,or in combination,in patients with Crohn＇s disease.

Roles of NAMPT and NAD decline in patho⁃genesis of Parkinson disease in mice

OBJECTIVE Nicotinamide phos⁃phoribosyltransferase(NAMPT)is the key enzyme for the synthesis of nicotinamide ade⁃nine dinucleotide(NAD)in the salvaging pathway.NAD is an essential co-enzyme of multiple enzymes involved in cell metabolism and important enzymes such as sirtuins.The level of both NAMPT and NAD decreases upon aging,which may cause neuronal degeneration.However,the roles of NAMPT and NAD in Par⁃kinson disease(PD)remain unknown.This study was to explore the roles of NAMPT and NAD decline in the pathogenesis of PD in mice.METOHDS Floxed nampt gene C57BL/6J mice,including Namptwt/wt,Namptflox/wt and Namptflox/flox,were used.The rAAV-hSyn-Cre-WPRE pA or rAAV-TH-Cre-WPRE pA adeno-associated virus(AAV)was used to conditioning knockout nampt gene in neurons or dopaminergic neurons,respectively.At 2,4,6,and 8 weeks after AAV injection,the motor deficits of mice were evaluat⁃ed.Immunofluorescence and immunohistochem⁃istry were used to evaluate the neuronal injury.Transmission electron microscope was used to evaluate the axonal degeneration.RESULTS The knockout of nampt gene induced dopaminer⁃gic neuron loss in substantia nigra at 4 weeks but not 2 weeks after AAV injection.At 8 weeks after AAV injection,the Namptflox/flox mice showed a significantly decrease in motor activity in an open-field than Namptwt/wt and Namptflox/wt mice.And some Namptflox/flox mice showed spin behav⁃ior at 6-8 weeks after AAV injection.The dopa⁃minergic neurons in substantia nigra and ventral tegmental area are more susceptible to the knockout of nampt gene than the non-dopaminer⁃gic neurons.Transmission electron microscope examine showed degenerative changes of the myelin in striatum at 4 weeks after AAV injection for the Namptflox/flox mice.The orally supplementary of NAD precursor,nicotinamide ribose,improved the motor activity and decreased neuronal injury for the nampt gene knockout mice.CONCLU⁃SION Decline of NAMPT and NAD in dopaminer⁃gic neurons is a risk for developing PD,and NAD precursors might be a new strategy for treatment of PD.

Conditioning knockout of nampt gene in mouse hippocampus neuron induces neuro⁃degeneration and cognitive deficiency

OBJECTIVE Nicotinamide phos⁃phoribosyltransferase(NAMPT)is the key en⁃zyme in the NAD(nicotinamide adenine dinucleo⁃tide)salvaging synthesis pathway.The level of NAMPT and NAD decreases during ageing,which causes neurodegenerative diseases.How⁃ever,the study of neuron-and region-specific ge⁃netic disturbance of NAMPT on cognition impair⁃ment is still lacking.This study was to explore the consequences and mechanisms of hippo⁃campus CA1 neuron-specific knockout of NAMPT on mouse cognitive functions.METH⁃ODS Floxed three-month old Nampt(Namptflox/flox)mice were used,and injected rAAV-hSyn-Cre-APRE-pA into the hippocampus CA1 region to specifically knockout the nampt gene.The learn⁃ing and memory of mice was determined at one-month after the intracerebral injection of AAV.We used immunofluorescence and trans⁃mission electron microscopy to detect neuronal injury.Western blotting and ELISA were used to measure the change of protein level and small molecule level.RESULTS One month after the knockout of nampt gene,the level of NAD signifi⁃cantly decreased in mouse hippocampus.The hippocampus dependent cognition of mice was also significantly decreased when compared to the wild type mice.However,the locomotor ac⁃tivity and anxiety behavior remained un⁃changed.Though there was no neuronal loss,and the neuronal cell bodies remained morpholog⁃ically intact.The level of Tau and MAP2 signifi⁃cantly decreased and degenerative change was found by using transmission electron micro⁃scope,which indicating the injury of both den⁃drites and axons.Meanwhile,the neuronal injury increased the neuroinflammation indicated by the activation of astrocyte and microglia.CON⁃CLUSION The decline of NAMPT and NAD causes neurodegeneration and cognition impair⁃ment of mice.

Improvement of the Specificity of Surface Plasmon Resonance with BSA-modified Chip

A chip was modified with bovine serum albumin （BSA）, then interaction between glutathione （GSH） immobilized on the top of BSA and glutathione-S-transferase （GST） was examined, using surface plasmon resonance （SPR）. The SPR results showed that BSA-modified chip was effective not only in binding the target proteins but also in suppressing the nonspecific binding （NSB） of proteins.