Agonists of the opioid δ-receptor improve irritable bowel syndrome-like symptoms via the central nervous system.

Background And Purpose: Irritable bowel syndrome (IBS) is a common condition that is challenging to treat, and novel drugs are needed for this condition. Previously, a chronic vicarious social defeat stress (cVSDS) mouse model exhibits IBS-like symptoms. Also agonists of the opioid δ-receptor exert anti-stress effects in rodents with minimal adverse effects.

Fentanyl Analogs Exert Antinociceptive Effects via Sodium Channel Blockade in Mice.

The formalin test is one approach to studying acute pain in rodents. Similar to formalin, injection with glutamate and veratrine can also produce a nociceptive response. This study investigated whether opioid-related compounds could suppress glutamate- and veratrine-induced nociceptive responses in mice at the same dose.

Further evidence for blood-to-brain influx of unconjugated bile acids by passive diffusion: Determination of their brain-to-serum concentration ratios in rats by LC/MS/MS.

Bile acids (BAs) reside in the brain and are probably involved in some neurological disorders. The view that most of unconjugated BAs in the brain are derived across the blood-brain barrier from the periphery by passive diffusion depending on their hydrophobicity is currently dominant, but some studies have made conflicting claims. In this study, the correlation analysis between the rat brain and serum levels of unconjugated BAs with a wider range of hydrophobicity was conducted to obtain further evidence about the blood-to-brain influx of unconjugated BAs by passive diffusion.

Drugs possessing aryloxypropanamine pharmacophore, duloxetine, dapoxetine and propranolol, increase allopregnanolone in rat brain: Possible involvement of allopregnanolone in their central nervous system effects.

Allopregnanolone (AP) is a neurosteroid synthesized in the brain and a positive allosteric modulator of γ-aminobutyric acid (GABA) type A receptors. Some drugs possessing the aryloxypropanamine (AOPA) pharmacophore, such as fluoxetine, exert their central nervous system (CNS) effects by increasing the brain AP. Although duloxetine (DLX), dapoxetine (DPX), atomoxetine (ATX) and propranolol (PRL) also possess the AOPA pharmacophore and are used to treat some psychiatric disorders, the capabilities of these drugs to increase the brain AP and the possible involvement of AP in their CNS effects remain to be fully elucidated.

Fucosylated heparan sulfate from the midgut gland of Patinopecten yessoensis.

The structural and functional relationships of glycosaminoglycans (GAGs) derived from marine organisms have been investigated, suggesting that marine invertebrates, particularly Bivalvia, are abundant sources of highly sulfated or branched GAGs. In this study, we identified a novel fucosylated heparan sulfate (Fuc-HS) from the midgut gland of the Japanese scallop, Patinopecten yessoensis. Scallop HS showed resistance to GAG-degrading enzymes, including chondroitinases and heparinases, and susceptibility to heparinases increased when scallop HS was treated with mild acid hydrolysis, which removes the fucosyl group.

Caffeine-Supplemented Diet Prevents Fatigue-Like Behavior in Tumor-Bearing Mice.

Caffeine is a widely consumed stimulant, known for its positive effects on physical and mental performance. These effects are potentially beneficial for ameliorating cancer-related fatigue, which affects the quality of life of patients with cancer. This study aimed to determine the anti-fatigue and antitumor effects of caffeine in tumor-bearing mice.

High-frequency ultrasound exposure improves depressive-like behavior in an olfactory bulbectomized rat model of depression.

Objectives: According to previous studies, ultrasound exposure appears to be a noninvasive method for modulating brain activity related to cognition and consciousness; however, its effects on emotional states remain unclear. Therefore, an animal model is required in which the effects and effect mechanisms of ultrasound exposure can be investigated. Thus, we used olfactory bulbectomized rats as an animal model of depression and investigated their emotional state following ultrasound exposure.

Preparation and Evaluation of Hydrogel Film Containing Tramadol for Reduction of Peripheral Neuropathic Pain.

To develop and assess new dosage forms for the alternative to existing oral medication for peripheral neuropathy, a hydrogel film in the skin patch formation containing tramadol hydrochloride (TRA), a water-soluble drug used as an analgesic, was prepared and evaluated. A hydrogel film composed of 20%(w/w) hydroxypropyl methylcellulose (HPMC) irradiated with electron beams had high transparency and elasticity similar to commercially available wound dressings and soft tissues, suggesting that it is a suitable substrate for TRA. The inclusion of TRA was enabled by immersing the HPMC hydrogel film in TRA aqueous solution.

Interleukin 6/gp130 axis promotes neural invasion in pancreatic cancer.

Background: Nerve invasion (N-inv) is an important prognostic factor in pancreatic ductal adenocarcinoma (PDAC). Elucidation of circulating N-inv stimulators could provide deeper insights and novel perspectives for PDAC therapy. The interleukin (IL)-6/gp130 axis was evaluated in this study as a candidate N-inv stimulator.

Effect of Sucrose on Cisplatin-induced Fatigue-like Behavior in Mice: Comparison With Fructose and Glucose.

Background/aim: Fatigue is the most common symptom in patients with cancer undergoing radiation therapy or cancer chemotherapy. However, cancer-related fatigue remains undertreated and poorly understood.

Materials And Methods: Mice were administered a single dose of cisplatin (10 mg/kg, intraperitoneally) or saline (as a control) and then treated with sucrose, fructose, glucose (each at 500 or 5,000 mg/kg, orally), or saline (control) daily for 4 days.

Alfaxalone improved in acute stress-induced tactile hypersensitivity and anxiety-like behavior in mice.

Stress has been shown to affect brain activity and exert potent and complex modulatory effects on pain. Several behavioral tests have shown that acute stress produces hyperalgesia, depending on the stress conditions. In the present study, we investigated the effects of single restraint stress on the tactile threshold and anxiety sensitivity in mice.

Cold-Restraint Stress-Induced Ultrasonic Vocalization as a Novel Tool to Measure Anxiety in Mice.

Ultrasonic vocalization (USVs) is a promising tool to measure behavioral anxiety in rodents as USV recording is noninvasive, behaviorally relevant, ethological, and reproducible. Studies reporting the effects of stress-induced USVs in adult mice remain limited and debated. We investigated the conditions under which mice emit aversive USVs and evaluated the effects of psychiatric drugs on stress-induced USVs.

Clinical and Tumor Characteristics of Patients with High Serum Levels of Growth Differentiation Factor 15 in Advanced Pancreatic Cancer.

We aimed to evaluate the association of circulating growth differentiation factor 15 (GDF-15) with cachexia symptoms and the biological activity of advanced pancreatic cancer (APC). Treatment-naïve patients with liver metastasis of APC or with benign pancreatic disease were retrospectively analyzed. Clinical data, blood samples, and biopsy specimens of liver metastasis were collected prior to anti-cancer treatment.

A 3-styrylchromone converted from trimebutine 3D pharmacophore possesses dual suppressive effects on RAGE and TLR4 signaling pathways.

Receptor for advanced glycation end-products (RAGE) and Toll-like receptors (TLRs) are potential therapeutic targets in the treatment of acute and chronic inflammatory diseases. We previously reported that trimebutine, a spasmolytic drug, suppresses RAGE pro-inflammatory signaling pathway in macrophages. The aim of this study was to convert trimebutine to a new small molecule using in silico 3D pharmacophore similarity search, and dissect the mechanistic anti-inflammatory basis.

Glyoxalase 1 and protein kinase Cλ as potential therapeutic targets for late-stage breast cancer.

Cancer cells upregulate the expression levels of glycolytic enzymes in order to reach the increased glycolysis required. One such upregulated glycolytic enzyme is glyoxalase 1 (GLO 1), which catalyzes the conversion of toxic methylglyoxal to nontoxic S-D-lactoylglutathione. Protein kinase Cλ (PKCλ) is also upregulated in various types of cancer and is involved in cancer progression.

Differences in the antinociceptive effects of serotonin-noradrenaline reuptake inhibitors via sodium channel blockade using the veratrine test in mice.

Antidepressants exert their analgesic effects by inhibiting the reuptake of noradrenaline. Several antidepressants have been shown to block the sodium channels, which might contribute to their analgesic potency. The aim of this study was to determine whether serotonin-noradrenaline reuptake inhibitors (SNRIs) could produce antinociceptive effects via sodium channel blockade using the veratrine test in mice.

Trimebutine attenuates high mobility group box 1-receptor for advanced glycation end-products inflammatory signaling pathways.

We previously identified papaverine as an inhibitor of receptor for advanced glycation end-products (RAGE) and showed its suppressive effect on high mobility group box 1 (HMGB1)-mediated responses to inflammation. Here, we found trimebutine to be a 3D pharmacophore mimetics of papaverine. Trimebutine was revealed to have more potent suppressive effects on HMGB1-induced production of pro-inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-α in macrophage-like RAW264.

Indirect exposure to socially defeated conspecifics using recorded video activates the HPA axis and reduces reward sensitivity in mice.

Rodents perceive the emotional states of conspecifics using vision. In the present study, we demonstrated that exposure to the video-recorded distress of conspecifics induces stress responses in male C57BL/6J mice. A single exposure to a video-recorded scene of the social defeat stress (SDS) increased plasma corticosterone levels in these mice.

Antinociceptive activity of the novel RAGE inhibitor, papaverine, in a mouse model of chronic inflammatory pain.

Extracellular high-mobility group box 1 (HMGB1) is known to mediate the inflammatory response through pattern recognition receptors, including the receptor for advanced glycation end products (RAGE) or the toll-like receptors (TLRs). The aim of the present study was to investigate whether papaverine, a novel RAGE inhibitor, could suppress inflammatory pain in mice after several time points, which was induced by the injection of complete Freund's adjuvant (CFA). We also investigated the influence of redox modulation during a state of chronic inflammatory pain.

Synergistic Antinociceptive Activity of Tramadol/Acetaminophen Combination Mediated by μ-Opioid Receptors.

We investigated whether tramadol could suppress both neuropathic and inflammatory pain in mice at the same dose level. We also examined the effects of drugs metabolized by glucuronidase, such as acetaminophen (ACAP), indomethacin, probenecid, and valproate, on the antinociceptive activity of tramadol. The administration of 5.

The Putative Glyoxalase 1 Inhibitor Piceatannol Exhibits Both Anxiolytic-like and Antitumor Effects in Mice.

Background/aim: This study aimed to determine the anxiolytic effect of a putative glyoxalase 1 inhibitor, piceatannol, as well as its antitumor activities on the stress-induced tumor growth of Lewis lung carcinoma.

Materials And Methods: The anxiolytic activities of piceatannol (1-30 mg/kg) were assessed using the elevated plus maze (EPM) test. We also evaluated the pharmacological modulation of stress-induced tumor growth; the mice were treated with piceatannol (3 and 30 mg/kg) from the 10 day till the 19 day after administration of the LLC cells.

Benzothiazepines, diltiazem and JTV-519, exert an anxiolytic-like effect via neurosteroid biosynthesis in mice.

We investigated whether benzothiazepines could produce anxiolytic effects via allopregnanolone (ALLO) biosynthesis in mice. We compared the behavioral effects caused by benzothiazepines to those caused by carbamazepine and sodium valproate. We found that a pretreatment with finasteride (a 5 alpha-reductase inhibitor) suppressed carbamazepine-induced anxiolytic effects but not the effects of sodium valproate.

Japanese Herbal Medicine Ninjinyoeito Mediates Its Orexigenic Properties Partially by Activating Orexin 1 Receptors.

Cancer cachexia is highly prevalent in patients with progressive cancer and is characterized by decreased food consumption, and body weight. Japanese herbal medicine Ninjinyoeito (NYT), composed of 12 herbal crude drugs, is prescribed in Asian countries to improve several symptoms such as anorexia and fatigue, which are commonly observed in patients with cancer cachexia. However, the action mechanisms of NYT in improving anorexia or fatigue in patients with cancer are not clear.

The effects of emotional stress are not identical to those of physical stress in mouse model of social defeat stress.

In this study, we investigated the effects of emotional stress and physical stress using the social defeat stress (SDS) model in mice. Male C57BL/6 J mice were attacked by male non-retired ICR mice for 10 min daily for 10 days (physical stress; PS), while the other cohort of mice witnessed the defeat (emotional stress; ES). As a result, both PS and ES mice exhibited decreased social behavior in the social interaction test (SIT) and increased immobility in the forced swim test (FST).

Selective agonists of the δ-opioid receptor, KNT-127 and SNC80, act differentially on extinction learning of contextual fear memory in mice.

We reported previously that KNT-127 and SNC80, selective agonists of the δ-opioid receptor (DOP), had potent anxiolytic-like effects in rodents. In this study, we evaluated whether KNT-127 and SNC80 influence extinction learning of contextual fear memory in the mice fear conditioning test. On day 1, the mice were contextually conditioned with eight trials (footshock; 0.