Previous studies reported that capsaicin potentiates AF508 mutant cystic fibrosis transmembrane conductance regulator(CFTR) channel gating defect by transfected cell-based assays. It has been postulated that orally ...
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Previous studies reported that capsaicin potentiates AF508 mutant cystic fibrosis transmembrane conductance regulator(CFTR) channel gating defect by transfected cell-based assays. It has been postulated that orally ingested capsaicin may conceptually be used to develop a therapeutic strategy to treat gastrointestinal disorders in CF patients. We tried to reproduce and extend those pre-clinical data of previous studies. Cell-based fluorescence func- tional measurements in Fischer thyroid epithelial cells(FRT) expressing CFTR showed no effect of capsaicin on potentiating AF508-CFTR, while genistein showed a strongly positive activity. Studies show that capsaicin and dihy- drocapsaicin activated cAMP-prestimulated wild-type CFTR in a dose-dependent manner with a maximal response of 70% of that activated by genistein, thus gave an apparent EC50 of (40.4±6.8)μmol/L and (150.2±7.4) μtmol/L respectively. Preliminary study shows that the binding sites for capsaicin and dihydrocapsaicin may be probably partially overlapped with that for genistein because the maximal activation of wild-type CFTR with genistein is partially blocked by caosaicin and dihydrocapsaicin.
The difficulty in estimating ages of regional landslides hampers to assess frequency of landslides and hence to quantitatively assess regional landslide *** this study,we used radiocarbon dating of organic sediment on...
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The difficulty in estimating ages of regional landslides hampers to assess frequency of landslides and hence to quantitatively assess regional landslide *** this study,we used radiocarbon dating of organic sediment on boulder rock varnish to estimate landslide ages in Langxian(LX)arid region in southeastern *** of rock varnish with organic sediment were collected on site for radiocarbon dating,leading to landslide ages from 1880±30 to 18,430±30 yr *** measure surface roughness characteristics of 109 remotely-mapped large bedrock landslide deposits,we estimated average standard deviation of slope(SDS)over an area of~640 km^(2) by calculating the slope gradient of each raster cell and using a rectangular moving window method in Arc Map from a 5 m-resolution Digital Elevation Model generated from helicopterobtained *** estimated landslide ages(t)with average surface roughness of mapped landslide deposits(R)quantified by SDS,we fit an exponential landslide deposits surface roughness-age function(t=1.47×10^(6)×e^(-1).46R,r2=0.63)that was used to estimate regional landslide ages in *** conclude that three periods with clusters of regional landslides in LX were revealed by different surface roughness of landslide deposits combing roughness-age function,with the values of 5563-7455 yr B.P.,1724-4151 yr B.P.,and 960-1287 yr B.P..Furthermore,we used our estimates of landslide ages to quantify landslide erosion rates of three corresponding hillslopes in LX ranging from 0.50 to 2.42 mm *** rock varnish radiocarbon dating provides us a feasible option for timing regional landslides of arid regions,the epistemic uncertainty in the dating method should arouse our attention,which could be reduced by increasing the number of samples.
Theophylline has been widely used in the'treatment of airway disease but molecular mechanism has not been clearly elucidated. Previous studies have manifested that theophylline increases intracellular cAMP concentra-...
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Theophylline has been widely used in the'treatment of airway disease but molecular mechanism has not been clearly elucidated. Previous studies have manifested that theophylline increases intracellular cAMP concentra- tion. Because cystic fibrosis transmembrane conductance regulator(CFTR) is a cAMP-dependent Cl- channel that plays key roles in fluid secretion in vivo, we postulated that theophylline activates CFTR channel gating. We found (1) theophylline stimulated CFTR-mediated anion transport in a concentration-dependent manner, and CFTR specific blocker completely reversed the effect; (2) theophylline had no effect on △F508 or G551D mutant CFTR chloride channel activity; (3) theophylline had additive effect with forskolin(FSK) and 3-isobutyl-xanthin(IBMX), thus a direct binding activation mechanism was suggested. In conclusion, the results may provide a clue to elucidating the molecular mechanism of theophylline activities and theophylline may present a novel lead drug in treating CFTR-related disease.
Macrophages undergo dynamic transitions between M1 and M2 states, exerting profound influences on both inflammatory and regenerative processes. The biocompatible and wound-healing properties of decellularized amniotic...
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Macrophages undergo dynamic transitions between M1 and M2 states, exerting profound influences on both inflammatory and regenerative processes. The biocompatible and wound-healing properties of decellularized amniotic membrane(d AM) make it a subject of exploration for its potential impact on the anti-inflammatory response of macrophages. Experimental findings unequivocally demonstrate that d AM promotes anti-inflammatory M2 polarization of macrophage, with its cytokine-rich content posited as a potential mediator. The application of RNA sequencing unveils differential gene expression, implicating the hypoxia inducible factor-1α(HIF-1α) signaling pathway in this intricate interplay. Subsequent investigation further demonstrates that d AM facilitates anti-inflammatory M2 polarization of macrophage through the upregulation of epidermal growth factor(EGF), which, in turn, activates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) pathway and stabilizes HIF-1α. This cascade results in a noteworthy augmentation of anti-inflammatory gene expression. This study significantly contributes to advancing our comprehension of d AM's immunomodulatory role in tissue repair, thereby suggesting promising therapeutic potential.
The combination of photodynamic therapy(PDT) and chemodynamic therapy(CDT) in tumor treatment has attracted considerable ***,tumor hypoxia and glutathione(GSH) overproduction in the tumor tissue restricted the p...
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The combination of photodynamic therapy(PDT) and chemodynamic therapy(CDT) in tumor treatment has attracted considerable ***,tumor hypoxia and glutathione(GSH) overproduction in the tumor tissue restricted the progress of their ***,a Mn-porphyrinic metal-organic framework(Mn-TCPP) was constructed by the one-pot method and further used for immobilizing glucose oxidase(GOx) to obtain GOx@*** would rapidly exhaust endogenous glucose into hydrogen peroxide(H2O2) and gluconic acid,thus shutting off the energy supply of tumor cells for starvation ***-TCPP catalyzed H2O2to produce oxygen,regulating the hypoxic tumor microenvironment and in turn improving1O2generation under laser ***,Mn-TCPP can reduce reactive oxygen species consumption owing to the redox reaction between Mn3+and GSH,thus greatly enhancing ***,benefiting from GOx-mediated starvation therapy,Mn2+produced by Mn3+reduction can react with sufficient intracellular H2O2to generate ·OH with high cytotoxicity through a Fenton-like *** treatment by GOx@Mn-TCPP under laser irradiation in vitro,the cell viability of 4T1 and A549 tumor cells reached to 20%,reflecting GOx@Mn-TCPP could give full play to the advantages of PDT/CDT/starvation *** results in vivo demonstrated that GOx@Mn-TCPP mediated synergistic cascade therapy could significantly inhibit tumor growth and improve the therapeutic effect.
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