Controlling Chemoselectivity in Ruthenium(II)-Induced Cyclization of Aniline-Functionalized Alkynes.

The cyclization of heteroatom-functionalized alkynes induced by d-transition-metal centers has traditionally been associated with the vinylidene pathway. However, recent evidence suggests that d-transition-metal centers can also activate alkynes through non-vinylidene pathways. In this study, we conducted a comprehensive experimental and theoretical investigation into the reactions between the Ru(II) complex [Ru([9]aneS3)(bpy)(OH)] and 2-alkynylanilines.

Ruthenafuran Complexes Supported by the Bipyridine-Bis(diphenylphosphino)methane Ligand Set: Synthesis and Cytotoxicity Studies.

Mononuclear and dinuclear Ru(II) complexes -[Ru(κ-dppm)(bpy)Cl] (), -[Ru(κ-dppe)(bpy)Cl] () and [Ru(bpy)(μ-dpam)(μ-Cl)](Cl) ([](Cl)) were prepared from the reactions between (Cl), (S)-[Ru(bpy)(dmso-)Cl] and diphosphine/diarsine ligands (bpy = 2,2'-bipyridine; dppm = 1,1-bis(diphenylphosphino)methane; dppe = 1,2-bis(diphenylphosphino)ethane; dpam = 1,1-bis(diphenylarsino)methane). While methoxy-substituted ruthenafuran [Ru(bpy)(κ-dppe)(C^O)] ([]; C^O = anionic bidentate [(OMe)CHC(Ph)] chelate) was obtained as the only product in the reaction between and phenyl ynone HC≡C(C=O)Ph in MeOH, replacing with led to the formation of both methoxy-substituted ruthenafuran [Ru(bpy)(κ-dppm)(C^O)] ([]) and phosphonium-ring-fused bicyclic ruthenafuran [Ru(bpy)(P^C^O)Cl] ([]; P^C^O = neutral tridentate [(Ph)CHP(Ph)CHC(Ph)] chelate). All of these aforementioned metallafuran complexes were derived from Ru(II)-vinylidene intermediates.

The Paddington International Virtual Chromoendoscopy Score in ulcerative colitis exhibits very good inter-rater agreement after computerized module training: a multicenter study across academic and community practice (with video).

Background And Aims: Electronic virtual chromoendoscopy (EVC) can demonstrate ongoing disease activity in ulcerative colitis (UC), even when Mayo subscores suggest healing. However, applicability of EVC technology outside the expert setting has yet to be determined.

Methods: Fifteen participants across 5 centers reviewed a computerized training module outlining high-definition and EVC (iScan) colonoscopy modes.

Impaired Transmigration of Myeloid-Derived Suppressor Cells across Human Sinusoidal Endothelium Is Associated with Decreased Expression of CD13.

Human monocytic myeloid-derived suppressor cells (MO-MDSCs) within the hepatic compartment suppress inflammation and impair immune surveillance in liver cancer. It is currently not known whether recruitment of MO-MDSCs from blood via hepatic sinusoidal endothelium (HSEC) contributes to their enrichment within the hepatic compartment. We compared the transmigratory potential of MO-MDSCs and monocytes after adhesion to hepatic endothelial monolayers in flow-based assays that mimic in vivo shear stress in the sinusoids.

Single-gene association between GATA-2 and autoimmune hepatitis: A novel genetic insight highlighting immunologic pathways to disease.

Background & Aims Autoimmune hepatitis (AIH), an immune-mediated liver disease, originates as a consequence of interacting genetic and environmental risk factors. Treatment remains non-specific and prone to side effects. Deficiencies in regulatory T cell (Treg) function are hypothesized to contribute to the pathogenesis of AIH.

Bidirectional transendothelial migration of monocytes across hepatic sinusoidal endothelium shapes monocyte differentiation and regulates the balance between immunity and tolerance in liver.

Unlabelled: Monocytes are versatile cells that can fulfill proinflammatory and anti-inflammatory functions when recruited to the liver. Recruited monocytes differentiate into tissue macrophages and dendritic cells, which sample antigens and migrate to lymph nodes to elicit T-cell responses. The signals that determine monocyte differentiation and the role of hepatic sinusoidal endothelial cells (HSECs) in this process are poorly understood.

CMV infection of human sinusoidal endothelium regulates hepatic T cell recruitment and activation.

Background & Aims: Human cytomegalovirus infection (HCMV) is associated with an increased morbidity after liver transplantation, by facilitating allograft rejection and accelerating underlying hepatic inflammation. We hypothesized that human hepatic sinusoidal endothelial cells infected with HCMV possess the capacity to modulate allogeneic T cell recruitment and activation, thereby providing a plausible mechanism of how HCMV infection is able to enhance hepatic immune activation.

Methods: Human hepatic sinusoidal endothelial cells were isolated from explanted livers and infected with recombinant endotheliotropic HCMV.

Contact-dependent depletion of hydrogen peroxide by catalase is a novel mechanism of myeloid-derived suppressor cell induction operating in human hepatic stellate cells.

Myeloid-derived suppressor cells (MDSC) represent a unique cell population with distinct immunosuppressive properties that have been demonstrated to shape the outcome of malignant diseases. Recently, human hepatic stellate cells (HSC) have been reported to induce monocytic-MDSC from mature CD14(+) monocytes in a contact-dependent manner. We now report a novel and unexpected mechanism by which CD14(+)HLADR(low/-) suppressive cells are induced by catalase-mediated depletion of hydrogen peroxide (H2O2).

Non-enzymatic dissociation of human mesenchymal stromal cells improves chemokine-dependent migration and maintains immunosuppressive function.

Background Aims: Human bone marrow-derived mesenchymal stromal cells (MSC) can suppress inflammation; therefore their therapeutic potential is being explored in clinical trials. Poor engraftment of infused MSC limits their therapeutic utility; this may be caused by MSC processing before infusion, in particular the method of their detachment from culture.

Methods: Enzymatic methods of detaching MSC (Accutase and TrypLE) were compared with non-enzymatic methods (Cell Dissociation Buffer [CDB], ethylenediamine tetra-acetic acid and scraping) for their effect on MSC viability, chemokine receptor expression, multi-potency, immunomodulation and chemokine-dependent migration.

Optimising risk stratification in primary biliary cirrhosis: AST/platelet ratio index predicts outcome independent of ursodeoxycholic acid response.

Background & Aims: Outcomes in primary biliary cirrhosis (PBC) can be predicted by biochemical response to ursodeoxycholic acid (UDCA). Such stratification inadequately captures cirrhosis/portal hypertension, recognised factors associated with adverse events.

Methods: We evaluated a cohort of PBC patients (n=386) attending the Liver Unit in Birmingham (derivation cohort), seeking to identify risk-variables associated with transplant-free survival independent of UDCA-response.

A method for conducting suppression assays using small numbers of tissue-isolated regulatory T cells.

The suppression assay is a commonly performed assay, measuring the ability of regulatory T cells (Treg) to suppress T cell proliferation. Most frequently, Treg are obtained from the peripheral blood or spleen. Lower yields are obtained by isolation from other tissues, rendering downstream suppression assays challenging to perform.

Monocyte subsets in human liver disease show distinct phenotypic and functional characteristics.

Unlabelled: Liver fibrosis is a wound healing response to chronic liver injury and inflammation in which macrophages and infiltrating monocytes participate in both the development and resolution phase. In humans, three monocyte subsets have been identified: the classical CD14++CD16-, intermediate CD14++CD16+, and nonclassical CD14+CD16++ monocytes. We studied the phenotype and function of these monocyte subsets in peripheral blood and liver tissue from patients with chronic inflammatory and fibrotic liver diseases.

Selective measurement of anti-tTG antibodies in coeliac disease and IgA deficiency: an alternative pathway.

Objective: To determine the ability of selective antibody testing to screen for coeliac disease in the presence of IgA deficiency and to define the sensitivity of a pathway using this method.

Method: All IgA and IgG anti-tTG tests performed at our centre between January 2008 and December 2009, using the Immunocap 250 analyser, were retrospectively reviewed. Positive results were correlated with histology.

The management of patients awaiting liver transplantation.

Since it was first performed in 1963, liver transplantation has become the only effective curative treatment in patients with liver failure. During the interval between being added to the waiting list and receiving a graft, the patient's condition may deteriorate as a result of disease progression or complications of the underlying liver disease. Both may result in death, removal from the waiting list because of futility of the procedure or, a worsened outcome following transplantation.

Recurrent nonviral liver disease following liver transplantation.

Recurrent disease after liver transplantation is well recognized and remains a potential cause of premature graft loss. The rates of recurrence are difficult to establish because of the lack of consistency in diagnostic criteria and approaches to diagnosis. Owing to the fact that recurrent parenchymal disease may occur in the presence of normal liver tests, those centers that use protocol biopsies will report greater rates of recurrence.