Willoughbylohse6519

The kappa opioid receptor is a constituent of the endogenous opioid analgesia system widely expressed in somatosensory nervous pathways and also in endometrial tissues. This work investigates the possible involvement of kappa opioid receptor on the nociceptive, behavioral and histopathological manifestations of endometriosis in a murine model. Female mice receiving endometrial implants develop a persistent mechanical hypersensitivity in the pelvic area that is stronger during the estrus phase of the estrous cycle. The kappa opioid receptor agonist U50,488H produces a dose-dependent relief of this mechanical hypersensitivity, regardless of the cycle phase. Repeated exposure to a low dose of U50,488H (1 mg/kg/day s.c. for one month) provides sustained relief of mechanical hypersensitivity, without tolerance development or sedative side effects. Interestingly, this treatment also inhibits a decreased rearing behavior associated with spontaneous pain or discomfort in endometriosis mice. This KOR-mediated pain relief does not prevent the anxiety-like behavior or the cognitive impairment exhibited by endometriosis mice, and the growth of endometriotic cysts is also unaltered. These data provide evidence of strong pain-relieving properties of kappa opioid receptor stimulation in female mice with endometriosis pain. The persistence of affective and cognitive manifestations suggests that these comorbidities are independent of pelvic pain and simultaneous treatment of these comorbidities may be necessary for successful management of endometriosis.Alzheimer's disease (AD) is a neurodegenerative disease, the main pathological features include deposition of neurofibrillary tangles composed of the abnormally hyperphosphorylated tau protein and plaques deposition composed of β-amyloid (Aβ) peptide. MicroRNAs and aberrant glycosylation both play key roles in a variety of diseases, especially AD. Our previous study showed that N-acetylglucosaminyltransferase III (GnT-III) was expressed strongly in AD model mice. GnT-III is a glycosyltransferase responsible for synthesizing a bisecting N-acetylglucosamine residue. Here, we report the potential therapeutic effects of microRNA-23b (miR-23b) against AD by targeting GnT-III. In this study, the role of miR-23b in GnT-III-mediated amelioration of AD-related symptoms and pathologies, and mechanisms were investigated. We used Aβ1-42-induced mouse and PC12 cell models to evaluate the effects of miR-23b on cognitive impairment, neurotoxicity, tau, and amyloid pathology. Bioinformatics analysis showed that GnT-III may be targeted by miR-23b, and it was verified by dual-luciferase reporter gene assays. Furthermore, a mechanistic study showed that activation of the Akt/GSK-3β signaling pathway can contribute to tau-lesion inhibition by miR-23b, and miR-23b can also restrain oxidative stress by altering Aβ-precursor protein processing. Taken together, we conclude that overexpression of miR-23b can interrupt the pathogenesis of AD.Communication between nerve cells depends on the balance between excitatory and inhibitory circuits. GABA, the major inhibitory neurotransmitter, regulates this balance and insufficient GABAergic activity is associated with numerous neuropathological disorders including pain. Of the various GABAA receptor subtypes, the δ-containing receptors are particularly interesting drug targets in management of chronic pain. These receptors are pentameric ligand-gated ion channels composed of α, β and δ subunits and can be activated by ambient levels of GABA to generate tonic conductance. this website However, only a few ligands preferentially targeting δ-containing GABAA receptors have so far been identified, limiting both pharmacological understanding and drug-discovery efforts, and more importantly, understanding of how they affect pain pathways. Here, we systemically review and discuss the known drugs and ligands with analgesic potential targeting δ-containing GABAA receptors and further integrate the biochemical nature of the receptors with clinical perspectives in pain that might generate interest among researchers and clinical physicians to encourage analgesic discovery efforts leading to more efficient therapies.Scorpionism is a public health burden in Brazil. Tityus bahiensis is responsible for most accidents in the Southeastern region of Brazil. Here, the hyperalgesic mechanisms of Tityus bahiensis venom were investigated, focusing on the role of pro-inflammatory cytokines (tumor necrosis factor alpha [TNF-α] and interleukin 1 beta [IL-1β]) and activation of the transcription factor NFκB. Intraplantar (i.pl.) administration of Tityus bahiensis venom (0.2, 0.6, 1.2 and 2.4 μg/20 μL i.pl.) induced mechanical hyperalgesia and thermal hyperalgesia. The 2.4 μg dose of Tityus bahiensis venom induced overt pain-like behavior and increased myeloperoxidase (MPO) and N-acetyl-beta-D-glucosaminidase (NAG) activities, TNF-α and IL-1β levels in the paw tissue. Systemic pre-treatment with etanercept (soluble TNF-α receptor; 10 mg/kg), IL-1ra (IL-1 receptor antagonist; 30 mg/kg) and pyrrolidine dithiocarbamate (PDTC, nuclear factor kappa B [NFκB] inhibitor; 100 mg/kg) inhibited Tityus bahiensis venom-induced mechanical and thermal hyperalgesia, MPO and NAG activity and overt pain-like behavior. These data demonstrate the involvement of TNF-α and IL-1β signaling as well as NFκB activation in Tityus bahiensis venom-induced mechanical and thermal hyperalgesia, overt pain-like behavior, and MPO activity and NAG activity, indicating thus, that targeting these mechanisms might contribute to reducing the pain in this scorpionism.The regulation of tolerable levels of ochratoxin A in food for human and animal consumption has been defined in some countries. To meet these levels, simpler, more efficient, and faster analytical methods are being developed to facilitate the identification of this dangerous contaminant in food. Here, we combined gold nanoparticles (AuNPs) with anti-ochratoxin A (OTA) IgG to detect elementary levels of OTA based on Localized Surface Plasmon Resonance. AuNPs were prepared with trisodium citrate and characterized by UV-visible spectroscopy, X-ray, dynamic light scattering, and transmission electron microscopy. The conjugation of AuNPs to IgG anti-OTA was confirmed by bathochromic shift (UV-vis) and RAMAN spectroscopy. The sensitivity of the nanosensor was investigated by measuring LSPR band λmax shifts. Our results suggest this assay is highly sensitive, with a lower detection limit of about 0.001 pg mL-1. The LSPR nanosensor reduced detection limits by roughly 10 times compared to other methods. We demonstrated that the approach investigated here is a rapid and sensitive method for OTA detection.