Toll-like receptor 7 is overexpressed in the bladder of Hunner-type interstitial cystitis, and its activation in the mouse bladder can induce cystitis and bladder pain

Abstract: Toll-like receptor 7 (TLR7) is associated with the pathophysiology of systemic lupus erythematosus and Sjögren syndrome, well-known diseases accompanying interstitial cystitis (IC). We studied TLR7 expression in the bladder of patients with Hunner-type IC (HIC) and its functional roles in bladder inflammation and nociception using mice. Bladder biopsy specimens were obtained from patients with HIC. Specimens from the noncancerous portion of the bladder of patients with bladder cancer served as controls. The specimens were examined by immunohistochemistry and real-time polymerase chain reaction of TLR7. Loxoribine (LX), a TLR7 agonist, was instilled in the bladder of C57BL/6N female mice, and TLR7-mRNA expression and histological changes of the bladder, bladder pain–like licking behavior, voiding behavior, cystometry, and bladder afferent nerve activities were investigated. The effects of hydroxychloroquine, a TLR7 antagonist, on the LX-induced changes on cystometry and voiding behavior were studied. The number of TLR7 immuno-reactive cells and the mRNA expression of TLR7 were significantly increased in HIC specimens. Intravesical instillation of LX induced edema, congestion, inflammation, and significantly increased TLR7-mRNA expression in the mouse bladder. Loxoribine-instillation also significantly increased licking behavior, voiding frequency, and afferent nerve activities associated with decreased single-voided volume and intercontraction interval of ...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

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ConclusionsThese observations suggest that SYD is effective in the enhancement of antioxidant ability via activation of Nrf2 pathway and the up-regulation of Nrf2-downstream phase II enzymes expression. The anti-inflammation and antioxidant action of SYD together contributes to the prevention and treatment of ulcerrelated colorectal cancer.Graphical abstract
Source: Journal of Ethnopharmacology - Category: Drugs & Pharmacology Source Type: research
In this study, a novel vitamin E succinate-based formulation of Ir (VES-Ir) combined with nanoscaled characteristics and synergistic combination was constructed through esterification. The conjugation makes amphiphilic VES-Ir prodrug self-assemble into nanoparticles with a fine diameter (VES-Ir NPs, 75.4 nm) of spherical morphology. Furthermore, VES-Ir NPs with a 1:1 drug-to-drug ratio was demonstrated to possess respectable physiological stability within 72 h test, while can react to pH/esterase-sensitive drug release in lysosomes internalized into tumor cells, potentially highlighting their alleviating side effects. Comp...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research
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Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research
Publication date: April 2020Source: Biomedicine &Pharmacotherapy, Volume 124Author(s): Danielle Kamato, Peter J. LittleAbstractThis review will cover the signalling pathways leading to the phosphorylation of the Smad linker region independent of Smad carboxy terminal phosphorylation. Characterising Smad linker region as a signalling pathway in its own right will encourage comprehensive signalling studies to provide solutions for successful discovery and exploitation of drug targets. The review describes Smad transcription factor signalling distinct from Transforming Growth Factor (TGF)-β signalling. Novel signalli...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
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Source: Expert Opinion on Drug Delivery - Category: Drugs & Pharmacology Authors: Source Type: research
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Source: Research in Autism Spectrum Disorders - Category: Psychiatry Source Type: research
Authors: Hou T, Fan Y, Dan W, Liu B, Wang Z, Zeng J, Li L Abstract Chaperone-mediated autophagy (CMA), a selective form of autophagy, where cellular proteins with KFERQ-like motif are targeted to the lysosome for degradation, is necessary to maintain cellular homeostasis. The role of CMA in neurodegenerative diseases has been extensively studied in the past decades, with defects in the pathway being strongly associated with disease. Recently, accumulating evidence has demonstrated a consistent increase in basal CMA activity in a wide array of cancer cell lines and human tumor biopsies, suggesting a potential link b...
Source: Histology and Histopathology - Category: Cytology Tags: Histol Histopathol Source Type: research
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Source: Reports of Practical Oncology and Radiotherapy - Category: Cancer & Oncology Source Type: research
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Source: Practical Radiation Oncology - Category: Cancer & Oncology Source Type: research
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Source: Journal of the American Academy of Child and Adolescent Psychiatry - Category: Psychiatry Tags: Correction Source Type: research
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