![]() As a key tool in liver homeostasis, the secretion of bicarbonate in the intrahepatic biliary epithelium is tightly regulated by ormones and neuropeptides, such as secretin, which induces choleresis by stimulating the Cl −/HCO 3 − exchanger activity in cholangiocytes. This concert of flows is key in the regulation of intracellular pH (pHi). The presence and functioning of two acid extruders, namely, the NHE-1 Na +/H + exchanger isoform 1, also know as solute carrier family 9 member A1 (SLC9A1) and the Na +/HCO 3 − cotransporter, balance the activity of the anion exchanger, as demonstrated in rodent cholangiocytes. Actually, the excretion plays a crucial role in the intrahepatic biliary epithelium, mainly driven by the apical Na-independent Cl −/HCO 3 −exchanger, which is identified as isoform AE2 in rodents and humans, also know as solute carrier family 4 member 2 (SLC4A2) and is functionally coupled with the cystic fibrosis transmembrane regulator (CFTR). The functioning of biliary extraction is driven by the differential potential across the cell membrane due to the ATP-dependent basal-lateral Na +/H + pump. Intrahepatic biliary epithelium exert a pivotal barrier function against the harsh environment of the bile mainly due to an active bicarbonate excretion, the so-called protective “bicarbonate umbrella”. Cholangiopaties are major indications for orthotropic liver transplantation. ![]() Graphical abstractīiliary tree lined by cholangiocytes and peribiliary glands is primarily involved in certain cholestasis liver diseases named cholangiopathies. A mouse model of cholangiopathy treated with NHs/dex shows a reduction in markers of hepatocellular injury compared to control groups (NHs, dex, or sham group). In conclusion, we believe that the NHs/dex formulation is a suitable candidate to be investigated in preclinical models of cholangiopathies. Primary and immortalized human cholangiocytes treated with NHs/dex show an increase in the functional marker expression of NHE1 cholangiocytes compared to control groups. In this study, the steroid dexamethasone was loaded into nanohydrogels (or nanogels, NHs), in order to investigate corticosteroid-induced increased activities of transport processes driving bicarbonate excretion in the biliary epithelium (NHE-1 isoform) and to evaluate the effects of dexamethasone-loaded NHs (NHs/dex) on liver injury induced by experimental cholestatis. Our results showed that NHs and NHs/dex do not reduce cell viability in vitro in human cholangiocyte cell lines. Increasing the delivery of steroids to the liver may result in three beneficial effects: increase in the choleresis, treatment of the autoimmune or inflammatory liver injury and reduction of steroids’ systemic harmful effects. We have previously reported that bile ducts isolated from rats treated with dexamethasone or budesonide showed an enhanced activity of the Na +/H + exchanger isoform 1 (NHE1) and Cl −/HCO 3 − exchanger protein 2 (AE2) . Recent reports indicate that budesonide, a corticosteroid with high receptor affinity and hepatic first pass clearance, increases the efficacy of ursodeoxycholic acid, a choleretic agent, in primary biliary cholangitis patients. I want to be able to do it once and that's it, not every time I generate a bibliography.A major function of the intrahepatic biliary epithelium is bicarbonate excretion in bile. It's all fine being able to do this once the bibliography is generated, but like many life science people I have lots of references that require this type of formating in the reference title. And, does Zotero assign a unique number that can then be used to track printed papers?įinally, I'd like to support the addition of italics, subscript, superscript, small caps and Greek (supported already?) in Zotero. So my questions are can I import the reference ID number from RM and have it in Zotero? This is vital to me successfully using Zotero. No doubt Zotero assigns some unique number, but how it does this is not evident, ie. ![]() When I print the references, I write this number on the paper and use it to track the reference. This automatically assigns a unique reference identification number. I'm in the process of switching over to Zotero, great to see such a cool program working with OpenOffice and Linux! the problem I have is that I routinely use Reference Manager.
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