Methoxyacetone revisited.

Conformational space of methoxyacetone (MA) was studied at the MP2/6-311++G(d,p) and DFT(B3LYP)/6-311++G(d,p) levels of theory. Computations predict MA to adopt four conformations, resulting from internal rotations around the O=C-C-O (Trans, Cis) and C-C-O-C (trans, gauche) dihedral angles. The Tt (Trans-trans) conformer is the most stable.

Extracellular CIRP Induces Calpain Activation in Neurons via PLC-IP-Dependent Calcium Pathway.

Abnormal calcium homeostasis, activation of protease calpain, generation of p25 and hyperactivation of cyclin-dependent kinase 5 (Cdk5) have all been implicated in the pathogenesis of neurogenerative diseases including Alzheimer's disease. We have recently shown that extracellular cold-inducible RNA-binding protein (eCIRP) induces Cdk5 activation via p25. However, the precise molecular mechanism by which eCIRP regulates calcium signaling and calpain remains to be addressed.

Prospective cohort study on the use of low molecular weight heparin calibrated anti-Xa assay for measurement of direct oral Xa inhibitors in ex vivo patient samples.

Drug-specific anti-Xa chromogenic assays are recommended for measurement of direct anti-Xa inhibitor levels but are not routinely available in many institutions. We performed a prospective study to determine: (1) the relationship between low molecular weight heparin (LMWH) calibrated anti-Xa measurements and apixaban or rivaroxaban levels measured using drug-specific anti-Xa assays and, (2) if a LMWH calibrated anti-Xa assay can be used to detect clinically significant apixaban or rivaroxaban levels. Haematology outpatients on rivaroxaban or apixaban for at least 72 h were recruited for this study.

Extracellular CIRP Activates the IL-6Rα/STAT3/Cdk5 Pathway in Neurons.

Extracellular cold-inducible RNA-binding protein (eCIRP) stimulates microglial inflammation causing neuronal damage during ischemic stroke and is a critical mediator of alcohol-induced cognitive impairment. However, the precise role of eCIRP in mediating neuroinflammation remains unknown. In this study, we report that eCIRP activates neurotoxic cyclin-dependent kinase-5 (Cdk5)/p25 through the induction of IL-6Rα/STAT3 pathway in neurons.

Vibrationally Induced Conformational Isomerization and Tunneling in Pyrrole-2-Carboxylic Acid.

The conformational behavior of carboxylic acids has attracted considerable attention, as it can be used as a gateway for the study of more complex phenomena. Here, we present an experimental and computational study of pyrrole-2-carboxylic acid (PCA) conformational space and the vibrational characterization of the compound by infrared spectroscopy. The possibility of promoting conformational transformations using selective vibrational excitation of the 2ν(OH) and 2ν(NH) stretching overtones is explored.

Potential Role of Extracellular CIRP in Alcohol-Induced Alzheimer's Disease.

Alzheimer's disease (AD) is the sixth leading cause of death in the USA and the most common form of neurodegenerative dementia. In AD, microtubule-associated protein tau becomes pathologically phosphorylated and aggregated, leading to neurodegeneration and the cognitive deficits that characterize the disease. Prospective studies have shown that frequent and heavy alcohol drinking is linked to early onset and increased severity of AD.

The protective role of human ghrelin in sepsis: Restoration of CD4 T cell proliferation.

Decrease of CD4 T cell numbers causes immunosuppression in sepsis. We previously showed the beneficial role of ghrelin in sepsis. We hypothesize that the protective outcome of ghrelin in sepsis is mediated partially through the restoration of CD4 T cells' proliferation.

Activation of Invariant Natural Killer T Cells Redirects the Inflammatory Response in Neonatal Sepsis.

Sepsis is the third leading cause of death in the neonatal population, due to susceptibility to infection conferred by immaturity of both the innate and adaptive components of the immune system. Invariant natural killer T (iNKT) cells are specialized adaptive immune cells that possess important innate-like characteristics and have not yet been well-studied in septic neonates. We hypothesized that iNKT cells would play an important role in mediating the neonatal immune response to sepsis.

DSP30 and interleukin-2 as a mitotic stimulant in B-cell disorders including those with a low disease burden.

Chromosome abnormalities detected during cytogenetic investigations for B-cell malignancy offer prognostic information that can have wide ranging clinical impacts on patients. These impacts may include monitoring frequency, treatment type, and disease staging level. The use of the synthetic oligonucleotide DSP30 combined with interleukin 2 (IL2) has been described as an effective mitotic stimulant in B-cell disorders, not only in chronic lymphocytic leukemia (CLL) but also in a range of other B-cell malignancies.

Mitigation of sepsis-induced inflammatory responses and organ injury through targeting Wnt/β-catenin signaling.

The Wnt/β-catenin pathway has been involved in regulating inflammation in various infectious and inflammatory diseases. Sepsis is a life-threatening condition caused by dysregulated inflammatory response to infection with no effective therapy available. Recently elevated Wnt/β-catenin signaling has been detected in sepsis.

PYR-41, A Ubiquitin-Activating Enzyme E1 Inhibitor, Attenuates Lung Injury in Sepsis.

During sepsis, systemic inflammation is observed and is associated with multiple organ failure. Activation of NF-κB is crucial for inducing inflammation, which is controlled by degradation of inhibitor molecules (IκB). The ubiquitination proteasome pathway is responsible for the regulation of protein turnover.

Cold-inducible RNA-binding protein activates splenic T cells during sepsis in a TLR4-dependent manner.

Cold-inducible RNA-binding protein (CIRP) is a novel inflammatory mediator that stimulates the release of proinflammatory cytokines from macrophages in sepsis. Given the immune dysregulation that characterizes sepsis, the effect of CIRP on other immune cells is an area of increasing interest that has not yet been studied. In the present study, we hypothesized that extracellular CIRP promotes activation of T lymphocytes in the spleen during sepsis.

Matrix isolation infrared spectroscopic study of 4-Pyridinecarboxaldehyde and of its UV-induced photochemistry.

The structure, infrared spectrum, barrier to internal rotation, and photochemistry of 4-pyridinecarboxaldehyde (4PCA) were studied by low-temperature (10K) matrix isolation infrared spectroscopy and quantum chemical calculations undertaken at both Moller-Plesset to second order (MP2) and density functional theory (DFT/B3LYP) levels of approximation. The molecule has a planar structure (C point group), with MP2/6-311++G(d,p) predicted internal rotation barrier of 26.6kJmol, which is slightly smaller than that of benzaldehyde (~30kJmol), thus indicating a less important electron charge delocalization from the aromatic ring to the aldehyde moiety in 4PCA than in benzaldehyde.

Regulation of SATB1 during thymocyte development by TCR signaling.

T lymphocyte development and differentiation is a multi-step process that begins in the thymus and completed in the periphery. Sequential development of thymocytes is dependent on T cell receptor (TCR) signaling and an array of transcription factors. In this study we show that special AT-rich binding protein 1 (SATB1), a T lineage-enriched chromatin organizer and regulator, is induced in response to TCR signaling during early thymocyte development.

Cold-inducible RNA-binding protein causes endothelial dysfunction via activation of Nlrp3 inflammasome.

Cold-inducible RNA-binding protein (CIRP) is a damage-associated molecular pattern (DAMP) molecule which stimulates proinflammatory cytokine release in hemorrhage and sepsis. Under these medical conditions, disruption of endothelial homeostasis and barrier integrity, typically induced by proinflammatory cytokines, is an important factor contributing to morbidity and mortality. However, the role of CIRP in causing endothelial dysfunction has not been investigated.

Exchange transfusion for neonate with haemolytic uremic syndrome.

Introduction: Haemolytic uremic syndrome (HUS) is one of the most common causes of acute renal failure in children but it is uncommon in newborns. To our knowledge only five cases have been reported so far (probably underreported). The known modalities of treatment include transfusion of plasma and plasmapheresis.

Milk fat globule epidermal growth factor-factor 8-derived peptide attenuates organ injury and improves survival in sepsis.

Introduction: Sepsis involves overwhelming inflammatory responses with subsequent immune-suppression that can lead to multiple organ dysfunction and ultimately death. Milk fat globule epidermal growth factor-factor 8 (MFG-E8) is a secretory protein found to have multiple biological activities against autoimmune and inflammatory diseases. MFG-E8 contains an Arg-Gly-Asp (RGD) motif involved in cell-cell and cell-matrix interactions.

β-Catenin is required for the differentiation of iNKT2 and iNKT17 cells that augment IL-25-dependent lung inflammation.

Background: Invariant Natural Killer T (iNKT) cells have been implicated in lung inflammation in humans and also shown to be a key cell type in inducing allergic lung inflammation in mouse models. iNKT cells differentiate and acquire functional characteristics during development in the thymus. However, the correlation between development of iNKT cells in the thymus and role in lung inflammation remains unknown.

Receptor-Interacting Protein Kinase 3 Deficiency Delays Cutaneous Wound Healing.

Wound healing consists of a complex, dynamic and overlapping process involving inflammation, proliferation and tissue remodeling. A better understanding of wound healing process at the molecular level is needed for the development of novel therapeutic strategies. Receptor-interacting protein kinase 3 (RIPK3) controls programmed necrosis in response to TNF-α during inflammation and has been shown to be highly induced during cutaneous wound repair.

Differential alterations of tissue T-cell subsets after sepsis.

Among immune cells in responding to sepsis, macrophages and neutrophils have been extensively studied, while the contribution of T lymphocytes and natural killer T (NKT) cells is less well characterized. Here we monitored tissue specific changes of T cell subsets in male C57BL/6 mice subjected to sham operation or cecal ligation and puncture (CLP) to induce polymicrobial sepsis. Thymus, spleen, liver, lungs and blood were processed and analyzed 20h later.

T cell factor-1 controls the lifetime of CD4+ CD8+ thymocytes in vivo and distal T cell receptor α-chain rearrangement required for NKT cell development.

Natural killer T (NKT) cells are a component of innate and adaptive immune systems implicated in immune, autoimmune responses and in the control of obesity and cancer. NKT cells develop from common CD4+ CD8+ double positive (DP) thymocyte precursors after the rearrangement and expression of T cell receptor (TCR) Vα14-Jα18 gene. Temporal regulation and late appearance of Vα14-Jα18 rearrangement in immature DP thymocytes has been demonstrated.

Blocking cold-inducible RNA-binding protein protects liver from ischemia-reperfusion injury.

Cold-inducible RNA-binding protein (CIRP) is a nuclear protein that has been recently identified as a novel inflammatory mediator in hemorrhagic shock and sepsis. We hypothesized that CIRP acts as a potent inflammatory mediator in hepatic ischemia-reperfusion (I/R), and thus blocking CIRP protects against I/R-induced liver injury. Male C57BL/6 mice were subjected to 70% hepatic ischemia by microvascular clamping of the hilum of the left and median liver lobes for 60 min, followed by reperfusion.

Early markers of occult megaloblastosis for low-cost detection of hyperhomocysteinemia in patients with ischaemic stroke: preventive approach for primary health care.

Recent studies have focussed on the association between elevated homocysteine levels with megaloblastic changes and thromboembolic events, but the relationship between occult megaloblastosis (with normal haemoglobin levels) and ischaemic stroke has not been widely explored. The objective of this study is to establish a simple and economical marker for the detection of occult megaloblastosis at the community health care level in developing countries. A hundred patients who met the inclusion criteria were studied.