On Difference Pattern Synthesis for Spherical Sensor Arrays.

An innovative method for synthesizing optimum difference patterns of the spherical sensor array is introduced, along with a sidelobe tapering technique. Firstly, we suggest employing the spherical harmonics of degree ±1 to synthesize the spherical array difference pattern; secondly, we study the mapping relationship between the difference pattern of the spherical sensor array and the difference pattern of the uniformly spaced linear array (ULA) with odd-numbered elements; finally, we enhance the Zolotarev difference pattern, which is a counterpart to the Dolph-Chebyshev sum pattern that traditionally allows synthesis only for ULA with even-numbered elements. Our modification extends its applicability to synthesize difference patterns for ULA with odd-numbered elements.

A randomized double-blind phase Ib clinical trial of SY-009 in patients with type 2 diabetes mellitus.

Introduction: SY-009 produces a hypoglycemic effect via inhibiting sodium/glucose cotransporter 1 (SGLT1) in type 2 diabetes mellitus (T2DM) patients. This randomized, double-blind, placebo-controlled, and multiple-dose escalation clinical trial aimed to evaluate the pharmacokinetic and pharmacodynamical characteristics as well as the safety and tolerability of SY-009 in T2DM patients.

Method: Fifty T2DM patients were randomized into experimental and placebo groups, and hospitalized for 9 days managed with a unified diet and rest management.

ZIGIR, a Granule-Specific Zn Indicator, Reveals Human Islet α Cell Heterogeneity.

Numerous mammalian cells contain abundant Zn in their secretory granules, yet available Zn sensors lack the desired specificity and sensitivity for imaging granular Zn. We developed a fluorescent zinc granule indicator, ZIGIR, that possesses numerous desired properties for live cell imaging, including >100-fold fluorescence enhancement, membrane permeability, and selective enrichment to acidic granules. The combined advantages endow ZIGIR with superior sensitivity and specificity for imaging granular Zn.

Amino Acid Transporter Slc38a5 Controls Glucagon Receptor Inhibition-Induced Pancreatic α Cell Hyperplasia in Mice.

Glucagon supports glucose homeostasis by stimulating hepatic gluconeogenesis, in part by promoting the uptake and conversion of amino acids into gluconeogenic precursors. Genetic disruption or pharmacologic inhibition of glucagon signaling results in elevated plasma amino acids and compensatory glucagon hypersecretion involving expansion of pancreatic α cell mass. Recent findings indicate that hyperaminoacidemia triggers pancreatic α cell proliferation via an mTOR-dependent pathway.

Attenuation Effect of Spinal Manipulation on Neuropathic and Postoperative Pain Through Activating Endogenous Anti-Inflammatory Cytokine Interleukin 10 in Rat Spinal Cord.

Objectives: The purpose of this study was to investigate roles of the anti-inflammatory cytokine interleukin (IL) 10 and the proinflammatory cytokines IL-1β and tumor necrosis factor α (TNF-α) in spinal manipulation-induced analgesic effects of neuropathic and postoperative pain.

Methods: Neuropathic and postoperative pain were mimicked by chronic compression of dorsal root ganglion (DRG) (CCD) and decompression (de-CCD) in adult, male, Sprague-Dawley rats. Behavioral pain after CCD and de-CCD was determined by the increased thermal and mechanical hypersensitivity of the affected hindpaw.

Wnt/Ryk signaling contributes to neuropathic pain by regulating sensory neuron excitability and spinal synaptic plasticity in rats.

Treating neuropathic pain continues to be a major clinical challenge and underlying mechanisms of neuropathic pain remain elusive. We have recently demonstrated that Wnt signaling, which is important in developmental processes of the nervous systems, plays critical roles in the development of neuropathic pain through the β-catenin-dependent pathway in the spinal cord and the β-catenin-independent pathway in primary sensory neurons after nerve injury. Here, we report that Wnt signaling may contribute to neuropathic pain through the atypical Wnt/Ryk signaling pathway in rats.

GLP-1 Receptor Mediated Targeting of a Fluorescent Zn(2+) Sensor to Beta Cell Surface for Imaging Insulin/Zn(2+) Release.

The pancreatic islet beta cell plays an essential role in maintaining the normal blood glucose level by releasing insulin. Loss of functional beta cell mass leads to diabetes—a disease affecting ∼9% of the population worldwide. There has been great interest and intense effort in developing imaging probes for monitoring islet beta cells, and glucagon-like peptide-1 receptor (GLP-1R) has emerged as a valuable biomarker for targeting beta cells.

WNT signaling underlies the pathogenesis of neuropathic pain in rodents.

Treating neuropathic pain is a major clinical challenge, and the underlying mechanisms of neuropathic pain remain elusive. We hypothesized that neuropathic pain-inducing nerve injury may elicit neuronal alterations that recapitulate events that occur during development. Here, we report that WNT signaling, which is important in developmental processes of the nervous system, plays a critical role in neuropathic pain after sciatic nerve injury and bone cancer in rodents.

Activation of cGMP-PKG signaling pathway contributes to neuronal hyperexcitability and hyperalgesia after in vivo prolonged compression or in vitro acute dissociation of dorsal root ganglion in rats.

Injury or inflammation affecting sensory neurons in the dorsal root ganglia (DRG) causes hyperexcitability of DRG neurons that can lead to spinal central sensitization and neuropathic pain. Recent studies have indicated that, following chronic compression of DRG (CCD) or acute dissociation of DRG (ADD) treatment, both hyperexcitability of neurons in intact DRG and behaviorally expressed hyperalgesia are maintained by activity in cGMP-PKG signaling pathway. Here, we provide evidence supporting the idea that CCD or ADD treatment activates cGMP-PKA signaling pathway in the DRG neurons.

Chronic compression or acute dissociation of dorsal root ganglion induces cAMP-dependent neuronal hyperexcitability through activation of PAR2.

Chronic compression (CCD) or dissociation of dorsal root ganglion (DRG) can induce cyclic adenosine monophosphate (cAMP)-dependent DRG neuronal hyperexcitability and behaviorally expressed hyperalgesia. Here, we report that protease-activated receptor 2 (PAR2) activation after CCD or dissociation mediates the increase of cAMP activity and protein kinase A (PKA) and cAMP-dependent hyperexcitability and hyperalgesia in rats. CCD and dissociation, as well as trypsin (a PAR2 activator) treatment, increased level of cAMP concentration, mRNA, and protein expression for PKA subunits PKA-RII and PKA-c and protein expression of PAR2, in addition to producing neuronal hyperexcitability and, in CCD rats, thermal hyperalgesia.

Reopening of ATP-sensitive potassium channels reduces neuropathic pain and regulates astroglial gap junctions in the rat spinal cord.

Adenosine triphosphate-sensitive potassium (K(ATP)) channels are suggested to be involved in pathogenesis of neuropathic pain, but remain underinvestigated in primary afferents and in the spinal cord. We examined alterations of K(ATP) channels in rat spinal cord and tested whether and how they could contribute to neuropathic pain. The results showed that protein expression for K(ATP) channel subunits SUR1, SUR2, and Kir6.

Topical application of compound Ibuprofen suppresses pain by inhibiting sensory neuron hyperexcitability and neuroinflammation in a rat model of intervertebral foramen inflammation.

Unlabelled: There is lack of evidence that topical application of an anti-inflammatory reagent could reduce pain due to intervertebral foramen (IVF) inflammation (IVFI). We investigated analgesic effects and underlying mechanisms of topical application of a compound ibuprofen cream (CIC) onto the surface of back skin covering the inflamed L(5) IVF in a rat model. Repetitive CIC treatment (~.

Thiamine suppresses thermal hyperalgesia, inhibits hyperexcitability, and lessens alterations of sodium currents in injured, dorsal root ganglion neurons in rats.

Background: B vitamins can effectively attenuate inflammatory and neuropathic pain in experimental animals, while their efficacy in treating clinical pain syndromes remains unclear. To understand possible mechanisms underlying B vitamin-induced analgesia and provide further evidence that may support the clinical utility of B vitamins in chronic pain treatment, this study investigated effects of thiamine (B1) on the excitability and Na currents of dorsal root ganglion (DRG) neurons that have been altered by nerve injury.

Methods: Nerve injury was mimicked by chronic compression of DRG in rats.

EphB receptor signaling in mouse spinal cord contributes to physical dependence on morphine.

Cellular and molecular mechanisms underlying opioid tolerance and dependence remain elusive. We investigated roles of EphB receptor tyrosine kinases--which play important roles in synaptic connection and plasticity during development and in the matured nervous system--in development and maintenance of physical dependence on morphine in the mouse spinal cord (SC). Spinal administration of an EphB receptor blocking reagent EphB2-Fc prevents and/or suppresses behavioral responses to morphine withdrawal and associated induction of c-Fos and depletion of calcitonin gene-related peptide.

Downregulated FKBP12.6 expression and upregulated endothelin signaling contribute to elevated diastolic calcium and arrhythmogenesis in rat cardiomyopathy produced by l-thyroxin.

Background: Dissociation of FKBP12.6 from RyR2 is considered as an important molecular event resulting in calcium leak and an increased risk in arrhythmogenesis. We hypothesized that augmented ventricular fibrillation (VF) on reperfusion of rat cardiomyopathy induced by l-thyroxin may result from elevated diastolic Ca(2+) levels due to dissociation (downregulation) of FKBP12.

Differing alterations of sodium currents in small dorsal root ganglion neurons after ganglion compression and peripheral nerve injury.

Voltage-gated sodium channels play important roles in modulating dorsal root ganglion (DRG) neuron hyperexcitability and hyperalgesia after peripheral nerve injury or inflammation. We report that chronic compression of DRG (CCD) produces profound effect on tetrodotoxin-resistant (TTX-R) and tetrodotoxin-sensitive (TTX-S) sodium currents, which are different from that by chronic constriction injury (CCI) of the sciatic nerve in small DRG neurons. Whole cell patch-clamp recordings were obtained in vitro from L4 and/or L5 dissociated, small DRG neurons following in vivo DRG compression or nerve injury.

EphrinB-EphB receptor signaling contributes to neuropathic pain by regulating neural excitability and spinal synaptic plasticity in rats.

Bidirectional signaling between ephrins and Eph receptor tyrosine kinases was first found to play important roles during development, but recently has been implicated in synaptic plasticity and pain processing in the matured nervous system. We show that ephrinB-EphB receptor signaling plays a critical role is induction and maintenance of neuropathic pain by regulating neural excitability and synaptic plasticity in the dorsal root ganglion (DRG) and the spinal dorsal horn (DH). Intrathecal application of blocking reagents for EphB-receptors, EphB1-Fc and EphB2-Fc chimeras inhibits the induction and maintenance of nerve injury-induced thermal hyperalgesia and mechanical allodynia.

Abrupt changes in FKBP12.6 and SERCA2a expression contribute to sudden occurrence of ventricular fibrillation on reperfusion and are prevented by CPU86017.

Aim: The occurrence of ventricular fibrillation (VF) is dependent on the deterioration of channelopathy in the myocardium. It is interesting to investigate molecular changes in relation to abrupt appearance of VF on reperfusion. We aimed to study whether changes in the expression of FKBP12.

Calcium antagonist property of CPU228, a dofetilide derivative, contributes to its low incidence of torsades de pointes in rabbits.

1. Torsades de pointes (TDP) is a severe adverse effect during the clinical use of dofetilide, a selective blocker of the rapid component of the delayed rectifier potassium channel (I(Kr)). The present study was designed to test whether CPU228, a derivative of dofetilide with calcium (Ca(2+)) antagonist properties, could reduce TDP without reducing the blockade of I(Kr).

[Inhibitory action of berberine on glucose absorption].

Aim: To study the absorption characteristics of berberine and its influence on glucose absorption.

Methods: Rat recirculating perfusion model was used to study berberine absorption characteristics and Caco-2 cell model was used to explore the influence of berberine on disaccharidase, using HPLC to assay the appearance of glucose to indicate enzyme activities.

Results: Berberine was found to be hardly absorbed in the intestine (less than 5% in 2.

The antihyperglycaemic activity of berberine arises from a decrease of glucose absorption.

The mechanism of action of berberine as an antihyperglycaemic agent was investigated in the Caco-2 cell line. Berberine was found to effectively inhibit the activity of disaccharidases in Caco-2 cells. It also decreased sucrase activity after preincubation with Caco-2 cells for 72 hours.