Novel Amidine Derivative K1586 Sensitizes Colorectal Cancer Cells to Ionizing Radiation by Inducing Chk1 Instability.

Checkpoint kinase 1 (Chk1) is a key mediator of the DNA damage response that regulates cell cycle progression, DNA damage repair, and DNA replication. Small-molecule Chk1 inhibitors sensitize cancer cells to genotoxic agents and have shown preclinical activity as single agents in cancers characterized by high levels of replication stress. However, the underlying genetic determinants of Chk1-inhibitor sensitivity remain unclear.

Design and synthesis of acrylate and acrylamide substituted pyrimidinediones as potential PPO herbicides.

PPO herbicides emerge to be widely use in the agricultural field and a focus of research to many scientists due to its environmentally-friendly properties. In lieu with this, this study presents acrylate and acrylamide substituted pyrimidinediones as PPO herbicide candidates. Most synthesized compounds exhibits herbicidal activities against both monocot and dicot weeds, especially, compound 5a which showed non-selective superior activity against the commercialized, Saflufenacil.

The CCL2 elevation in primary afferent fibers produces zymosan-induced hyperalgesia through microglia-mediated neuronal activation in the spinal dorsal horn.

Although C-C motif chemokine ligand 2 (CCL2) plays a critical role in the pathogenesis of neuropathic pain through neuron-microglia interactions, its pronociceptive function underlying inflammatory pain remains to be fully understood. The present study aimed to elucidate the potential role of CCL2 in pain sensitization following zymosan-induced inflammation. Intraplantar injection of zymosan into the rat hind paw significantly increased the expression of CCL2 in both dorsal root ganglions and the superficial dorsal horn.

Plug-Assisted Retrograde Transvenous Obliteration for the Treatment of Gastric Varices: The Role of Intra-Procedural Cone-Beam Computed Tomography.

Objective: To investigate the technical and clinical outcomes of plug-assisted retrograde transvenous obliteration (PARTO) for the treatment of gastric varices (GV) and to evaluate the role of intra-procedural cone-beam computed tomography (CBCT) performed during PARTO to confirm its technical success.

Materials And Methods: From January 2016 to December 2016, 17 patients with GV who had undergone PARTO were retrospectively evaluated. When the proximal part of the afferent vein was identified on a fluoroscopy, non-contrast CBCT images were obtained.

All-optical regenerator of multi-channel signals.

One of the main reasons why nonlinear-optical signal processing (regeneration, logic, etc.) has not yet become a practical alternative to electronic processing is that the all-optical elements with nonlinear input-output relationship have remained inherently single-channel devices (just like their electronic counterparts) and, hence, cannot fully utilise the parallel processing potential of optical fibres and amplifiers. The nonlinear input-output transfer function requires strong optical nonlinearity, e.

The spinal antinociceptive mechanism determined by systemic administration of BD1047 in zymosan-induced hyperalgesia in rats.

Although sigma-1 receptor (Sig-1R) antagonists have a potential antinociceptive effect in inflammatory diseases, the precise mechanism is not fully understood. The present study was aimed to elucidate the role of spinal neurons and microglia in the anti-nociceptive mechanism of BD1047 (a prototypical Sig-1R antagonist) using an inflammatory pain model based on intraplantar injection of zymosan. Oral pretreatment with BD1047 dose-dependently reduced zymosan-induced thermal and mechanical hyperalgesia as well as spinal neuronal activation including increased immunoreactivity of Fos, protein kinase C (PKC) and 'PKC-dependent phosphorylation of the NMDA receptor subunit 1' (pNR1).

Regulatory effect of bee venom on methamphetamine-induced cellular activities in prefrontal cortex and nucleus accumbens in mice.

Our previous studies demonstrated that subcutaneous injection of bee venom (BV) into the Zusanli (ST36) acupuncture point, namely BV acupuncture, dose-dependently prevents conditioned place preference (CPP) induced by repeated injection of methamphetamine (METH) in mice. To expand on our observations, the present study was designed to determine the suppressive mechanisms of BV acupuncture in the development of METH-induced CPP by evaluating the changes in expression of ΔFosB, phosphorylated extracellular signal-regulated kinase 1/2 (pERK), and phosphorylated calcium/calmodulin-dependent protein kinase type II (pCaMKII) in the prefrontal cortex (PFC) and nucleus accumbens (NAc) in mice. Pre-emptive treatment with BV at 30 min before repeated METH injection completely suppressed acquisition of CPP at the day 7 test session.

Inhibition of mitogen-activated protein kinases phosphorylation plays an important role in the anti-nociceptive effect of pregabalin in zymosan-induced inflammatory pain model.

Although pregabalin has been shown to have preclinical and clinical efficacy in neuropathic pain, the mechanism of its antinociceptive action is still unknown in other pain states. This study aimed to evaluate the antinociceptive effect of pregabalin and its underlying spinal mechanisms related to mitogen activated protein kinases (MAPKs) in neuron and microglia following intraplantar injection of zymosan model. Zymosan evoked thermal hyperalgesia, mechanical hyperalgesia, and mechanical allodynia starting from 1 h and persistent until 5 h post-injection, which were dose-dependently reversed by oral pretreatment of pregabalin (3, 10, and 30 mg/kg).

Chronic activation of sigma-1 receptor evokes nociceptive activation of trigeminal nucleus caudalis in rats.

Primary headache disorders, including migraine, are thought to be mediated by prolonged nociceptive activation of the trigeminal nucleus caudalis (TNC), but the precise mechanisms are poorly understood. Our past studies demonstrated that sigma-1 receptors (Sig-1R) facilitate spinal nociceptive transmission in several pain models. Based on these findings, this study asked if chronic activation of Sig-1R by intracisternal administration of the selective Sig-1R agonist, PRE084, produced TNC neuronal activation as a migraine trigger in rats.

Pain modality and spinal glia expression by streptozotocin induced diabetic peripheral neuropathy in rats.

Pain symptoms are a common complication of diabetic peripheral neuropathy or an inflammatory condition. In the most experiments, only one or two evident pain modalities are observed at diabetic peripheral neuropathy according to experimental conditions. Following diabetic peripheral neuropathy or inflammation, spinal glial activation may be considered as an important mediator in the development of pain.

Predictive factors for invasive intraductal papillary mucinous neoplasm of the pancreas.

Backgrounds/aims: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has malignant potential. Predicting invasive IPMN has proven difficult and controversial. We tried to identify predictive factors for invasive IPMN.

Sigma-1 Receptor Antagonist BD1047 Reduces Allodynia and Spinal ERK Phosphorylation Following Chronic Compression of Dorsal Root Ganglion in Rats.

Many therapeutic roles have been proposed for sigma-1 receptor (Sig-1R), but the involvement of Sig-1R in neuropathic pain has currently not been well explored. The present study aimed to evaluate the anti-nociceptive effect of Sig-1R antagonist (BD1047) in a rat model of chronic compression of the dorsal root ganglion (CCD), which is a model of human foraminal stenosis and radicular pain. When stainless steel rods were inserted into the intervertebral foramen of lumbar vertebrae 4 and 5, the CCD developed reliable mechanical (from 3 day) and cold allodynia (from 1 day) as compared with the sham operation group.

Effect of bee venom acupuncture on methamphetamine-induced hyperactivity, hyperthermia and Fos expression in mice.

Acupuncture has been used to treat drug addiction by nicotine, alcohol, cocaine and morphine. This study was designed to investigate the effect of bee venom (BV) acupuncture on hyperactivity and hyperthermia induced by acute exposure to methamphetamine (METH, 1mg/kg, s.c.

Bee venom suppresses methamphetamine-induced conditioned place preference in mice.

Objectives: Although acupuncture is most commonly used for its analgesic effect, it has also been used to treat various drug addictions including cocaine and morphine in humans. This study was designed to investigate the effect of bee venom injection on methamphetamine-induced addictive behaviors including conditioned place preference and hyperlocomotion in mice.

Methods: Methamphetamine (1 mg/kg) was subcutaneously treated on days 1, 3 and 5 and the acquisition of addictive behaviors was assessed on day 7.

The Antinociceptive Effect of Sigma-1 Receptor Antagonist, BD1047, in a Capsaicin Induced Headache Model in Rats.

Intracranial headaches, including migraines, are mediated by nociceptive activation of the trigeminal nucleus caudalis (TNC), but the precise mechanisms are poorly understood. We previously demonstrated that selective blockage of spinal sigma-1 receptors (Sig-1R) produces a prominent antinociceptive effect in several types of pain models. This study evaluates whether the Sig-1R antagonist (BD1047) has an antinociceptive effect on capsaicin (a potent C-fiber activator) induced headache models in rats.

Substantial role of locus coeruleus-noradrenergic activation and capsaicin-insensitive primary afferent fibers in bee venom's anti-inflammatory effect.

Several lines of evidence indicate significant interactions between the immune and nervous systems. Our recent study reveals that 'bee venom (BV) induced anti-inflammatory effect' (BVAI) was produced by sympathetic preganglionic neuronal activation and subsequent adrenomedullary catecholamine release in a zymosan-induced inflammation model. However, the specific peripheral input and the supraspinal neuronal systems that are involved in this BVAI remain to be defined.

Water soluble fraction (<10 kDa) from bee venom reduces visceral pain behavior through spinal alpha 2-adrenergic activity in mice.

We have previously shown that subcutaneous bee venom (BV) injection reduces visceral pain behavior in mice, but it is not clear which constituent of BV is responsible for its antinociceptive effect. In the present study, we now demonstrate that a water-soluble subfraction of BV (BVA) reproduces the antinociceptive effect of BV in acetic acid-induced visceral pain model. We further evaluated three different BVA subfractions that were separated by molecular weight, and found that only the BVAF3 subfraction (a molecular weight of <10 kDa) produced a significant antinociceptive effect on abdominal stretches and suppressed visceral pain-induced spinal cord Fos expression.

Antinociceptive mechanisms associated with diluted bee venom acupuncture (apipuncture) in the rat formalin test: involvement of descending adrenergic and serotonergic pathways.

In a previous report, subcutaneous injection of diluted bee venom (dBV) into a specific acupuncture point (Zusanli, ST36), a procedure termed apipuncture, was shown to produce an antinociceptive effect in the rat formalin pain model. However, the central antinociceptive mechanisms responsible for this effect have not been established. Traditional acupuncture-induced antinociception is considered to be mediated by activation of the descending pain inhibitory system (DPIS) including initiation of its opioidergic, adrenergic and serotonergic components.

Electroacupuncture ameliorates experimental colitis induced by acetic acid in rat.

The effect of electroacupuncture (EA) on experimental colitis was investigated in Sprague-Dawley rats. Colitis was induced by intracolonic instillation of 4% acetic acid. EA (2 Hz, 0.

Bee venom acupoint stimulation increases Fos expression in catecholaminergic neurons in the rat brain.

Fos immunocytochemistry was combined with tyrosine hydroxylase (TH) or dopamine-beta-hydroxylase (DBH) immunolabeling to examine brainstem catecholaminergic neuronal activation resulting from bee venom (BV) stimulation of the Zusanli acupoint (ST36) in Sprague-Dawley rats. BV injection into the Zusanli acupoint caused increased Fos expression in catecholaminergic neurons located in the hypothalamic arcuate nucleus (Arc), the dorsal raphe (DR), the A5 cell group (A5) and the locus coeruleus (LC). BV acupoint stimulation significantly increased Fos-TH double-labeled neurons in the Arc, LC and DR.

The water-soluble fraction of bee venom produces antinociceptive and anti-inflammatory effects on rheumatoid arthritis in rats.

We recently demonstrated that bee venom (BV) injection into the Zusanli acupoint produced a significantly more potent anti-inflammatory and antinociceptive effect than injection into a non-acupoint in a Freund's adjuvant induced rheumatoid arthritis (RA) model. However, the precise BV constituents responsible for these antinociceptive and/or anti-inflammatory effects are not fully understood. In order to investigate the possible role of the soluble fraction of BV in producing the anti-arthritic actions of BV acupuncture, whole BV was extracted into two fractions according to solubility (a water soluble fraction, BVA and an ethylacetate soluble fraction, BVE) and the BVA fraction was further tested.