The study explores whether miR-139-5p targeting LPAR4 affects epithelial-mesenchymal transition (EMT) and fibrosis in post-menopausal women with interstitial cystitis (IC) via the PI3K/Akt signaling pathway. Bladder tissues of IC and normal bladder tissues were collected. The pathology of bladder tissues was observed by HE, Masson and Picrosirius red staining. LPAR4 positive expression rate were determined by IHC. ELISA was performed to detect the levels of IL-6, IL-8, IL-10, and TNF-α. Rat IC models were randomized into seven different groups. miR-139-5p, LPAR1, LPAR2, LPAR3, LPAR4, LPAR5, P13K, Akt, E-cadherin, N-cadherin, Vimentin, TGF-β1, and CTGF expression were determined by RT-qPCR and Western blotting. Dual luciferase reporter gene assay verified that LPAR4 is a target gene of miR-139-5p. Fibrosis was a pathological manifestation of IC. The IC group showed higher LPAR4, PI3K, Akt, p-PI3K, p-Akt, N-cadherin, Vimentin, TGF-β1, and CTGF expression but lower miR-139-5p and E-cadherin expression than the normal group. The levels of IL-6, IL-8, IL-10, and TNF-α expression decreased while HB-EGF increased in the IC group in comparison of the normal group. Compared with the blank and NC groups, E-cadherin expression was increased in the miR-139-5p mimic and siRNA-LPAR4 groups, while LPAR4, PI3K, Akt, p-P13K, p-Akt, N-cadherin, Vimentin, TGF-β1, and CTGF expression were decreased. An opposite trend was found in the miR-139-5p inhibitor group. The miR-139-5p decreased in the miR-139-5p inhibitor + siRNA-LPAR4 and miR-139-5p inhibitor + wortmannin groups. Conclusively, miR-139-5p targeting LPAR4 inhibits EMT and fibrosis in post-menopausal IC women through the PI3K/Akt signaling pathway.
Introduction and hypothesis The objective was to assess whether telemedicine-based follow-up is equivalent to office-based follow-up in the early postoperative period after routine synthetic midurethral sling placement. Methods This is a prospective, international, multi-institutional, randomized controlled trial. Patients undergoing synthetic midurethral sling placement were randomized to 3-week postoperative telemedicine versus office-based follow-up. The primary outcome was the rate of unplanned events. Secondary outcomes included patient satisfaction, crossover from telemedicine to office-based follow-up, and compliance with 3- to 5-month office follow-up. Results We included 238 patients (telemedicine: 121 vs office: 117). No differences in demographics or medical comorbidities were noted between the study groups ( p = 0.09–1.0). No differences were noted in unplanned events: hospital admission, emergency department visit, or unplanned office visit or call (14% vs 12.9%, p = 0.85) or complications (9.9% vs 8.6%, p = 0.82). Both groups were equally “very satisfied” with their surgical outcomes (71.1% vs 69%, p = 0.2). Telemedicine patients were more compliant with 3- to 5-month office follow-up (90.1% vs 79.3%, p = 0.04). Conclusions After synthetic midurethral sling placement, telemedicine follow-up is a safe patient communication option in the early postoperative period. Telemedicine patients reported no difference in satisfaction compared with office-based follow-up but had greater compliance with 3- to 5-month follow-up.
Interstitial cystitis is associated with neurogenic inflammation and neuropathic bladder pain. Dual leucine zipper kinase (DLK) expressed in sensory neurons is implicated in neuropathic pain. We hypothesized that neuronal DLK is involved in the regulation of inflammation and nociceptive behavior in cystitis. Mice deficient in DLK in sensory neurons (cKO) were generated by crossing DLK floxed mice with mice expressing Cre recombinase under Advillin promoter. Cystitis was induced by cyclophosphamide (CYP) administration in mice. Nociceptive behavior, bladder inflammation, and pathology were assessed following cystitis induction in control and cKO mice. The role of DLK in CYP-induced cystitis was further determined by pharmacological inhibition of DLK with GNE-3511. Deletion of neuronal DLK attenuated CYP-induced pain-like nociceptive behavior and suppressed histamine release from mast cells, neuronal activation in the spinal cord, and bladder pathology. Mice deficient in neuronal DLK also showed reduced inflammation induced by CYP and reduced c-Jun activation in the dorsal root ganglia (DRG). Pharmacological inhibition of DLK with GNE-3511 recapitulated the effects of neuronal DLK depletion in CYP treatment mice. Our study suggests that DLK is a potential target for the treatment of neuropathic pain and bladder pathology associated with cystitis.
Simultaneous wireless information and power transfer (SWIPT) optimization with multiple objective function optimization is presented in the millimeter band in this paper. Three different objective functions that are used for harvest power (HP), capacity, and bit error rate (BER) were studied. There are three different nodes in real environment for wireless power transfer (WPT) and SWIPT. The channel estimation calculated by shooting and bouncing ray/image techniques includes multi-path, fading effect, and path-loss in the real environment. We applied beamforming techniques at the transmitter to focus the transmitter energy in order to reduce the multi-path effect and adjust the length of the feed line on each array element in order to find the extremum of the objective functions by the self-adaptive dynamic differential evolution (SADDE) method. Numerical results showed that SWIPT node cannot achieve good performance by single objective function, but wireless power transfer (WPT) can. Nevertheless, both WPT and SWIPT nodes can meet the criteria by the multiple objective function. The harvesting power ratio as well as the BER and capacity can be improved by the multiple objective function to an acceptable level by only reducing a little harvesting energy compared to the best harvesting energy for the single objective function. Finally, the multiple optimization function cannot merely provide good information quality for SWIPT node but achieve good total harvesting power for WPT and SWIPT node as well.
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