Synthesis, design, and antiproliferative evaluation of 6-(N-Substituted-methyl)pyrazolo[3,4-d]pyrimidines as the potent anti-leukemia agents.

Pyrazolopyrimidine derivatives, including pyrazolopyrimidines, 6-aminopyrazolopyrimidines, 6-[(formyloxy)methyl]pyrazolopyrimidines, 6-(hydroxymethyl)pyrazolopyrimidine, and 6-(aminomethyl)pyrazolopyrimidines have been successfully prepared and tested against NCI-H226, NPC-TW01, and Jurkat cancer cell lines. Among the tested pyrazolopyrimidine compounds, we found 6-aminopyrazolopyrimidines and 6-(aminomethyl)pyrazolopyrimidines with essential o-ClPh or p-ClPh substituted moieties on N-1 pyrazole ring exhibited the best IC inhibition activity for Jurkat cells. Furthermore, optimization of the SAR study on the C-6 position of pyrazolopyrimidine ring demonstrated that 6-(N-substituted-methyl)pyrazolopyrimidines 17b, 17d, and 19d possessed the significant IC inhibitory activity for the different leukemia cell lines, especially for Jurkat, K-562, and HL-60.

Synthesis, physicochemical characterization, and investigation of anti-inflammatory activity of water-soluble PEGylated 1,2,4-Triazoles.

A series of water-soluble PEGylated 1,2,4-triazoles 5-8 were successfully synthesized from methyl 5-(chloromethyl)-1-aryl-1H-1,2,4-triazole-3-carboxylates 1. All of the water-soluble PEGylated 1,2,4-triazoles were characterized by FT-IR and H NMR spectroscopy. The solubility, in vitro plasma stability, and anti-inflammatory activity were also determined and compared to original methyl 5-(halomethyl)-1-aryl-1H-1,2,4-triazole-3-carboxylates.

One-Pot Double Oxidation Synthesis of N-1-Piperidonyl Amides From N-1-Piperidinyl Amides with meta-Chloroperbenzoic Acid: Rimonabant Analogue as Model Study.

A simple and efficient one-pot oxidation synthesis of N-1-piperidonyl amides was successfully developed through the double oxidation of hydrazides (involving hydrazonium formation, azodioxy-carbonyl compounds generation, and α-carbon oxidation) by using meta-chloroperbenzoic acid (mCPBA). The convenient oxidation method was also extended to Rimonabant analogue. The lactam oxidized Rimonabant analogue was first successfully synthesized for demonstrating the construction and characterized by NMR spectroscopic methods and the single-crystal X-ray diffraction study (ORTEP).

Synthesis and anti-inflammatory activity evaluation of NO-releasing furoxan/1,2,4-triazole hybrid derivatives.

An efficient synthesis method was developed for furoxan/1,2,4-triazole hybrids 5a-k from methyl 5-(halomethyl)-1-aryl-1H-1,2,4-triazole-3-carboxylates 1 through two-steps reaction including hydrolyzation and esterification. All of the furoxan/1,2,4-triazole hybrid derivatives were characterized by spectroscopy. On the other hand, the influence of newly synthesized multi-substituted 1,2,4-triazoles on the exogenous NO release ability, in vitro and in vivo anti-inflammatory activity, and in silico predictions were experimentally evaluated.

Synthesis of β-Amino Carbonyl 6-(Aminomethyl)- and 6-(Hydroxymethyl)pyrazolopyrimidines for DPP-4 Inhibition Study.

Background: Type-2 diabetes is a chronic progressive metabolic disease resulting in severe vascular complications and mortality risk. Recently, DPP-4 inhibitors had been conceived as a favorable class of agents for the treatment of type 2 diabetes due to the minimal side effects.

Methods: Sitagliptin is the first medicine approved for the DPP-4 inhibitor.

Bioactivity Study of Tricyclic and Tetracyclic Genipin Derivatives as Anti-inflammatory Agents.

A series of genipin derivatives included tricyclic cyclopentaimidazopyridine, cyclopentapyridopyrimidine, octahydrocyclopentapyridodiazepine, and tetracyclic decahydrobenzoimidazocyclopentapyridine were synthesized and developed as anti-inflammatory agents. All of them were tested against NO production in LPS-induced RAW264.7 cells.

Efficacy and safety of lubiprostone for the treatment of functional constipation in Chinese adult patients: A multicenter, randomized, double-blind, placebo-controlled trial.

Objectives: Functional constipation is a gastrointestinal disorder prevalent around the world. Lubiprostone is the first locally acting type-2 chloride channel activator to be used for treating constipation. This study aimed to evaluate the efficacy and safety of lubiprostone in Chinese adults with functional constipation.

PIEZO ion channel is required for root mechanotransduction in .

Plant roots adapt to the mechanical constraints of the soil to grow and absorb water and nutrients. As in animal species, mechanosensitive ion channels in plants are proposed to transduce external mechanical forces into biological signals. However, the identity of these plant root ion channels remains unknown.

PIEZOs mediate neuronal sensing of blood pressure and the baroreceptor reflex.

Activation of stretch-sensitive baroreceptor neurons exerts acute control over heart rate and blood pressure. Although this homeostatic baroreflex has been described for more than 80 years, the molecular identity of baroreceptor mechanosensitivity remains unknown. We discovered that mechanically activated ion channels PIEZO1 and PIEZO2 are together required for baroreception.

Pancreatic T/histiocyte-rich large B-cell lymphoma: A case report and review of literature.

Primary pancreatic lymphoma (PPL) is an extremely rare form of extranodal malignant lymphoma. The most common histological subtype of PPL is diffuse large B cell lymphoma (DLBCL). In rare cases, PPL can also present as follicular lymphoma, small lymphocytic lymphoma, and T cell lymphoma either of non-Hodgkin's lymphoma or of Hodgkin's lymphoma.

The E3 ubiquitin ligase NEDD4 is translationally upregulated and facilitates pancreatic cancer.

Aim: To determine the regulation and function of the neural precursor cell expressed developmentally down regulated protein 4 (NEDD4) in PDAC and to determine its dependency on phosphatase and tensin homolog (PTEN) and PI3K/AKT signaling.

Methods: We investigated the expression of NEDD4 and the tumor suppressor PTEN in normal immortalized human pancreatic duct epithelial cell line and pancreatic adenocarcinoma (PDAC) cell lines. We further evaluated whether RNAi-mediated depletion of NEDD4 can attenuate PDAC cell proliferation and migration.

Neuroplastin Isoform Np55 Is Expressed in the Stereocilia of Outer Hair Cells and Required for Normal Outer Hair Cell Function.

Unlabelled: Neuroplastin (Nptn) is a member of the Ig superfamily and is expressed in two isoforms, Np55 and Np65. Np65 regulates synaptic transmission but the function of Np55 is unknown. In an N-ethyl-N-nitrosaurea mutagenesis screen, we have now generated a mouse line with an Nptn mutation that causes deafness.

Tissue acidosis induces neuronal necroptosis via ASIC1a channel independent of its ionic conduction.

Acidotoxicity is common among neurological disorders, such as ischemic stroke. Traditionally, Ca(2+) influx via homomeric acid-sensing ion channel 1a (ASIC1a) was considered to be the leading cause of ischemic acidotoxicity. Here we show that extracellular protons trigger a novel form of neuronal necroptosis via ASIC1a, but independent of its ion-conducting function.

Repeated pancreatitis-induced splenic vein thrombosis leads to intractable gastric variceal bleeding: A case report and review.

Gastric varices (GV) are one of the most common complications for patients with portal hypertension. Currently, histoacryl injection is recommended as the initial treatment for bleeding of GV, and this injection has been confirmed to be highly effective for most patients in many studies. However, this treatment might be ineffective for some types of GV, such as splenic vein thrombosis-related localized portal hypertension (also called left-sided, sinistral, or regional portal hypertension).

Activation of acid-sensing ion channels by localized proton transient reveals their role in proton signaling.

Extracellular transients of pH alterations likely mediate signal transduction in the nervous system. Neuronal acid-sensing ion channels (ASICs) act as sensors for extracellular protons, but the mechanism underlying ASIC activation remains largely unknown. Here, we show that, following activation of a light-activated proton pump, Archaerhodopsin-3 (Arch), proton transients induced ASIC currents in both neurons and HEK293T cells co-expressing ASIC1a channels.

Contrast enhanced computed tomography and reconstruction of hepatic vascular system for transjugular intrahepatic portal systemic shunt puncture path planning.

Aim: To describe a method for the transjugular intrahepatic portal systemic shunt (TIPS) placement performed with the aid of contrast-enhanced computed tomography (CECT) and three-dimensional reconstructed vascular images (3D RVIs), and to assess its safety and effectiveness.

Methods: Four hundred and ninety patients were treated with TIPS between January 2005 and December 2012. All patients underwent liver CECT and reconstruction of 3D RVIs of the right hepatic vein to portal vein (PV) prior to the operation.

Hepatoprotective effect of juglone on dimethylnitrosamine-induced liver fibrosis and its effect on hepatic antioxidant defence and the expression levels of α-SMA and collagen III.

The present study aimed to investigate the antifibrotic effects of juglone on dimethylnitrosamine (DMN)‑induced fibrosis in rats. Juglone, which is a quinone, significantly decreased DMN‑induced rat hepatic fibrosis, which was associated with increased superoxide dismutase (SOD) activity, decreased oxidative stress and reduced levels of α‑smooth muscle actin (α‑SMA) and collagen (Col) III in the liver. Serum levels of alanine aminotransferase, aspartate aminotransferase, hyaluronic acid, laminin, type III precollagen and type IV collagen were significantly reduced by treatment with juglone.

Acid-sensing ion channels: trafficking and pathophysiology.

Acid-sensing ion channels (ASICs) are proton-gated cation channels that are widely expressed in both the peripheral and central nervous systems. ASICs contribute to a variety of pathophysiological conditions that involve tissue acidosis, such as ischemic stroke, epileptic seizures and multiple sclerosis. Although much progress has been made in researching the structure-function relationship and pharmacology of ASICs, little is known about the trafficking of ASICs and its contribution to ASIC function.

Kainate receptor activation induces glycine receptor endocytosis through PKC deSUMOylation.

Surface expression and regulated endocytosis of glycine receptors (GlyRs) play a critical function in balancing neuronal excitability. SUMOylation (SUMO modification) is of critical importance for maintaining neuronal function in the central nervous system. Here we show that activation of kainate receptors (KARs) causes GlyR endocytosis in a calcium- and protein kinase C (PKC)-dependent manner, leading to reduced GlyR-mediated synaptic activity in cultured spinal cord neurons and the superficial dorsal horn of rat spinal cord slices.

Clinical effects and complications of TIPS for portal hypertension due to cirrhosis: a single center.

Aim: To determine the clinical effects and complications of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension due to cirrhosis.

Methods: Two hundred and eighty patients with portal hypertension due to cirrhosis who underwent TIPS were retrospectively evaluated. Portal trunk pressure was measured before and after surgery.

Quantification of serum hepatitis B surface antigen in predicting the response of pegylated interferon alfa-2a in HBeAg-positive chronic hepatitis B with prior lamivudine exposure.

Aims: Majority of previous studies of pegylated interferon α-2a (PegIFNα-2a) forced on naïve chronic hepatitis B (CHB) patients, and the data of PegIFNα-2a in therapy of patients with prior exposure to nucleos(t)ide analogues is rare. This study aimed to investigate the predictive role of serum quantitative hepatitis B surface antigen (HBsAg) in predicting sustained response of PegIFNα-2a in HBeAg-positive CHB patients with prior lamivudine exposure.

Methods: Forty-six patients with prior lamivudine exposure received PegIFNα-2a for 12 months and followed-up for 6 months.

Histamine up-regulates astrocytic glutamate transporter 1 and protects neurons against ischemic injury.

Astrocytic glutamate transporter 1 (GLT-1) is responsible for the majority of extracellular glutamate clearance and is essential for preventing excitotoxicity in the brain. Up-regulation of GLT-1 shows benefit effect on ischemia-induced neuronal damage. In present study, we examined the effect of histamine, a neurotransmitter or neuromodulator, on GLT-1 expression and function.