In recent years, games have been proven to be an effective tool in supplementing traditional teaching methods. Through game playing, students can strengthen their cognitive-recognition architecture and gain satisfaction as well a sense of achievement. This study presents conceptual framework for examining various strategies by which instructors both integrate into courses games' positive influence on students' learning motivations. We used flexible web-based instructional called the...

Ten-eleven translocation methylcytosine dioxygenase 1 (Tet1) mediates the conversion of 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine hmC), hence promoting DNA demethylation. Although recent studies have linked demethylation specific genes pain hypersensitivity, role spinal Tet1-dependent in nociception hypersensitivity development remains elusive. Here, we report correlated with behavioral allodynia, nerve ligation (SNL) upregulated Tet1 expression dorsal horn neurons that hydroxylate...

Oxidative stress is identified as a major inducer of retinal pigment epithelium (RPE) cell dysregulation and associated with age-related macular degeneration (AMD). The protection RPE disorders plays an essential role in the pathological progress diseases. pharmacological functions fucoxanthin, characteristic carotenoid, including anti-inflammatory antioxidant properties, may ameliorate outstanding bioactivity against premature senescence cellular dysfunction. This study demonstrates that...

In addition to the well-established advantage that strengthened pelvic musculature increases urethral resistance in stress urinary incontinence (SUI) patients, intra-vaginal electrical stimulation (iVES) has been shown preclinical studies improve bladder capacity via pudendal-hypogastric mechanism. This study investigated whether iVES also benefits storage SUI patients by focusing on compliance, a viscoelastic parameter critically defining bladder's function, clinical study. Moreover,...

Background Neuropathic pain presents a significant clinical challenge, with spinal cord epigenetic mechanisms playing critical role in its development. This study investigated the impact of nerve injury on Barrier-to-Autointegration Factor (BAF) rat dorsal horn. Methods Adult Sprague-Dawley rats underwent ligation (SNL) to model neuropathic pain. Pain behaviors were assessed using von Frey and burrow tests. Biochemical analyses measured mRNA protein expression Results SNL elevated BAF...

Abstract Background Methylone (3,4-methylenedioxy-N-methylcathinone) is a rapid-acting entactogen that has been shown to have significant benefits in patients with post-traumatic stress disorder and major depressive well tolerated phase 1 clinical trials. A recent preclinical study reported methylone produced robust antidepressant-like actions naï ve rats. However, its antidepressant effects on various stress-related psychopathologies other neuropsychological remain unclear. Aims &...

Abstract Background BTRX-246040, a nociceptin/orphanin FQ peptide receptor antagonist, is being developed for the treatment of depressive patients[1,2]. However, underlying mechanism this potential antidepressant still largely unclear. Here, we studied antidepressant-related actions BTRX- 246040 in ventrolateral periaqueductal gray (vlPAG). Methods The tail suspension test, forced swim female urine sniffing sucrose preference and learned helplessness (LH) combined with pharmacological...

Abstract Background: The histone deacetylases (HDACs) have been implicated in pain hypersensitivity. This study investigated the potential involvement of an HDAC4-related mechanism spinal nerve ligation (SNL)-induced nociceptive Methods: left L5 to L6 nerves 627 adult male Sprague–Dawley rats were surgically ligated. withdrawal threshold hind paws and abundances, cellular location, interactions proteins dorsal horn assayed before after surgery. 14-3-3β-targeting small-interfering RNA, a...

Abstract Melatonin ( N ‐acetyl‐5‐methoxytryptamine)/ MT 2 receptor‐dependent epigenetic modification represents a novel pathway in the treatment of neuropathic pain. Because spinal ten‐eleven translocation methylcytosine dioxygenase 1 (Tet1)‐dependent demethylation has recently been linked to pain hypersensitivity, we hypothesized that melatonin/ 2‐dependent analgesia involves Tet1‐dependent demethylation. Here, showed Tet1 gene transfer by intrathecal delivery Tet1‐encoding vectors naïve...

Melatonin (MLT; N-acetyl-5-methoxytryptamine) exhibits analgesic properties in chronic pain conditions. While researches linking MLT to epigenetic mechanisms have grown exponentially over recent years, very few studies investigated the contribution of MLT-associated modification states. Here, we report that together with behavioral allodynia, spinal nerve ligation (SNL) induced a decrease expression catalytic subunit phosphatase 2A (PP2Ac) and enhanced histone deacetylase 4 (HDAC4)...

We investigated the participation of cyclin-dependent kinase-5 (Cdk5)-mediated N-methyl-d-aspartate receptor (NMDAR) NR2B subunit phosphorylation in cross-organ reflex sensitization caused by colon irritation. The external urethral sphincter electromyogram (EUSE) activity evoked pelvic afferent nerve test stimulation (TS, 1 stimulation/30 s) and protein expression spinal cord dorsal root ganglion tissue (T13-L2 L6-S2 ipsilateral to stimulation) response mustard oil (MO) instillation were...

Recently, we demonstrated a spinal GABA(A) receptor (GABA(A)R)-dependent inhibition on the induction of repetitive stimulation-induced reflex potentiation. However, it remains unclear whether steroid hormones modulate such an inhibition. Here, show that progesterone is capable producing GABA(A)Rs-dependent potentiation by actions through neurosteroid metabolites. Progesterone (5mg/kg, twice daily for 4 days) up-regulates expression GABA(A)R alpha2, alpha3, alpha4 and delta subunits,...

TOC summary SGK1/GRASP-1/Rab4 participated in complete Freund’s adjuvant-induced inflammatory pain via regulating GluR1-containing AMPAR recycling at the dorsal horn neurons. The elusiveness of mechanism underlying is a major impediment developing effective clinical treatments. We examined whether phosphorylation spinal serum- and glucocorticoid-inducible kinase 1 (SGK1) downstream glutamate receptor interacting protein (GRIP)-associated protein-1 (GRASP-1)/Rab4-dependent...

The coupling of the spinal postsynaptic density-95 (PSD-95) with glutamatergic N -methyl- d -aspartate receptor NR2B subunit and subsequent phosphorylation contribute to pain-related plasticity. Increasing evidence reveals that kalirin, a Rho-guanine nucleotide exchange factor, modulates PSD-95-NR2B-dependent neuroplasticity. Our laboratory recently demonstrated serum-inducible glucocorticoid-inducible kinase 1 (SGK1) participates in inflammation-associated pain hypersensitivity by...

Emerging evidence has indicated that the pathogenesis of neuropathic pain is mediated by spinal neural plasticity in dorsal horn, which provides insight for analgesic therapy. Here, we report abundance tumor necrosis factor receptor-associated 2 and NcK-interacting kinase (TNIK), a presumed to regulate plasticity, was specifically enhanced ipsilateral horn neurons after nerve ligation (SNL; left L5 L6). Spinal TNIK-associated allodynia downstream TNIK–GluR1 coupling subsequent...

Fucoxanthin is a carotenoid with many pharmaceutical properties that found in brown seaweed. However, the effects of fucoxanthin on corneal innervation and intense eye pain have not been extensively examined. To clarify protective roles underlying mechanisms ocular lesions, we investigated beneficial by which ameliorates ultraviolet B (UVB)-induced denervation trigeminal pain. Treatment enhanced expression nuclear factor erythroid 2-related 2 cornea. Inhibition typical epithelial exfoliation...

Cross-organ sensitization between the uterus and lower urinary tract (LUT) underlies high concurrence of pelvic pain syndrome LUT dysfunctions, yet role gonadal steroids is still unknown. We tested hypothesis that cross-organ on pelvic-urethra reflex activity caused by uterine capsaicin instillation estrous cycle dependent. When compared with baseline (1.00 +/- 0.00 spikes/stimulation), significantly increased (45.42 9.13 spikes/stimulation, P < 0.01, n = 7) was corroborated an increase in...

Retromer, which crucially contributes to endosomal sorting machinery through the retrieval and recycling of signaling receptors away from degradation, has been identified as a critical element for glutamatergic-receptor-dependent neural plasticity at excitatory synapses. We observed it accompanied by behavioral allodynia; neuropathic injury time-dependently enhanced VPS26A SNX27 expression; VPS26A–SNX27 coprecipitation; VPS26A-positive, SNX27-positive, double-labeled immunoreactivity in...

Spinal plasticity, a key process mediating neuropathic pain development, requires ubiquitination-dependent protein turnover. Presynaptic active zone proteins have crucial role in regulating vesicle exocytosis, which is essential for synaptic plasticity. Nevertheless, the mechanism ubiquitination-regulated turnover of presynaptic progression spinal plasticity-associated remains unclear. Here, after research involving Sprague Dawley rats, we reported that nerve ligation (SNL), addition to...

Neuroligin-1 (NL1) forms a complex with the presynaptic neurexin-1β (Nrx1b), regulating clustering of N-methyl-D-aspartate receptors postsynaptic density-95 (PSD-95) to underlie learning-/memory-associated plasticity. Pain-related spinal neuroplasticity shares several common features The authors thereby investigated potential involvement NL1-related mechanism in nerve ligation (SNL)-associated allodynia.In 626 adult male Sprague-Dawley rats, withdrawal threshold and NL1, PSD-95,...

Inflammation and oxidative stress are closely related processes in the pathogenesis of various ocular diseases. Uveitis is a disorder uvea tissues that causes extreme pain, decreases visual acuity, can eventually lead to blindness. The pharmacological functions fucoxanthin, isolated from brown algae, induce variety therapeutic effects such as reduction repression inflammation reactions. However, specific anti-inflammatory fucoxanthin on pathogen-associated molecular pattern (PAMP)...

The microtubule-stabilizing drug paclitaxel (PTX) is an important chemotherapeutic agent for cancer treatment and causes peripheral neuropathy as a common side effect that substantially impacts the functional status quality of life patients. mechanistic role NIMA-related kinase 2 (NEK2) in progression PTX-induced neuropathic pain has not been established.Adult male Sprague-Dawley rats intraperitoneally received PTX to induce pain. protein expression levels dorsal root ganglion (DRG) animals...