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31.
32.
Yu Shi Yangwei Fan Yuan Hu Jiayu Jing Chuying Wang Yinying Wu Qianqian Geng Xuyuan Dong Enxiao Li Danfeng Dong 《Journal of cellular and molecular medicine》2020,24(1):760-771
High rates of de novo lipid synthesis have been discovered in certain kinds of tumours, including gallbladder cancer (GBC). Unlike several other tumours, GBC is highly insensitive to standard adjuvant therapy, which makes its treatment even more challenging. Although several potential targets and signalling pathways underlying GBC chemoresistance have been revealed, the precise mechanisms are still elusive. In this study, we found that α‐Mangostin, as a dietary xanthone, repressed the proliferation and clone formation ability, induced cell cycle arrest and the apoptosis, and suppressed de novo lipogenesis of gallbladder cancer cells. The underlying mechanisms might involve the activation of AMPK and, therefore, the suppression of SREBP1 nuclear translocation to blunt de novo lipogenesis. Furthermore, SREBP1 silencing by siRNA or α‐mangostin enhanced the sensitivity of gemcitabine in gallbladder cancer cells. In vivo studies also displayed that MA or gemcitabine administration to nude mice harbouring NOZ tumours can reduce tumour growth, and moreover, MA administration can significantly potentiate gemcitabine‐induced inhibition of tumour growth. Corroborating in vitro findings, tumours from mice treated with MA or gemcitabine alone showed decreased levels of proliferation with reduced Ki‐67 expression and elevated apoptosis confirmed by TUNEL staining, furthermore, the proliferation inhibition and apoptosis up‐regulation were obviously observed in MA combined with gemcitabine treatment group. Therefore, inhibiting de novo lipogenesis via targeting the AMPK/SREBP1 signalling by MA might provide insights into a potential strategy for sensitizing GBC cells to chemotherapy. 相似文献
33.
Meng-Juan Lin Lei Chen Zhen-Peng Huang Hu Qiu Bao-Ping Yu 《Journal of cellular physiology》2019,234(4):4291-4301
Acute cholecystitis is a common disease with gallbladder dysmotility. Disease pathogenesis involves immune cell infiltration as well as changes in gallbladder interstitial Cajal-like cells (ICLCs). However, it remains unclear if or how the immune cells affect ICLC morphology, density, distribution, and function in gallbladder tissue during acute cholecystitis. In this study, we explored the acute cholecystitis-related alterations in gallbladder ICLCs in a guinea pig model, focusing on the effects of neighboring neutrophils. Adult guinea pigs were randomly divided into four groups (control, 24 hr common bile duct ligation [CBDL], 48-hr CBDL, and antipolymorphonuclear neutrophil [PMN] treated) and analyzed using methylene blue staining and immunofluorescence. Gallbladder contractility was also monitored. To culture gallbladder ICLCs, collagenase digestion was performed on tissue from 10- to 15-day-old guinea pigs. Neutrophils isolated from the peripheral blood of experimental animals 48-hr postsurgery were also cocultured with the gallbladder ICLCs. Intracellular calcium was detected with Fluo-4 AM dye. Our results showed that gallbladder ICLC density significantly declined during acute cholecystitis and was accompanied by shortening of the cellular processes and damage to their network-like structure. However, pretreatment with anti-PMN partially prevented these changes. Gallbladder contraction was also significantly decreased during acute cholecystitis, and this appeared to be mediated by the neutrophils. Moreover, ICLCs cocultured with neutrophils also had shortened and reduced processes and impaired network-like structure formation. Intracellular calcium transient was less sensitive to contraction agonists and inhibitors when cocultured with neutrophils. Taken together, neutrophils greatly affect gallbladder ICLCs and dysmotility during acute cholecystitis. 相似文献
34.
Nandini A. Sahasrabuddhe Mustafa A. Barbhuiya Shushruta Bhunia Tejaswini Subbannayya Harsha Gowda Jayshree Advani Braj R. Shrivastav Sanjay Navani Pamela Leal Juan Carlos Roa Raghothama Chaerkady Sanjeev Gupta Aditi Chatterjee Akhilesh Pandey Pramod K. Tiwari 《Biochemical and biophysical research communications》2014
Gallbladder cancer is an uncommon but lethal malignancy with particularly high incidence in Chile, India, Japan and China. There is a paucity of unbiased large-scale studies investigating molecular basis of gallbladder cancer. To systematically identify differentially regulated proteins in gallbladder cancer, iTRAQ-based quantitative proteomics of gallbladder cancer was carried out using Fourier transform high resolution mass spectrometry. Of the 2575 proteins identified, proteins upregulated in gallbladder cancer included several lysosomal proteins such as prosaposin, cathepsin Z and cathepsin H. Downregulated proteins included serine protease HTRA1 and transgelin, which have been reported to be downregulated in several other cancers. Novel biomarker candidates including prosaposin and transgelin were validated to be upregulated and downregulated, respectively, in gallbladder cancer using tissue microarrays. Our study provides the first large scale proteomic characterization of gallbladder cancer which will serve as a resource for future discovery of biomarkers for gallbladder cancer. 相似文献
35.
The intra and extrahepatic bile ducts of the liver are developmentally distinct, and may be differentially affected by certain diseases. However, differences between intra and extrahepatic cholangiocytes, and between neonatal and adult cells, are not well understood.Methods for the isolation of cholangiocytes from intrahepatic bile ducts are well established1-4. Isolation of extrahepatic ductal cells, especially from the neonate, has not yet been described, although this would be of great benefit in understanding the differences between distinct cholangiocyte populations and in studying diseases such as biliary atresia that appear to target the extrahepatic ducts. Described here is an optimized technique to isolate both neonatal and adult mouse extrahepatic bile duct cells. This technique yields a pure cell population with minimal contamination from mesenchymal cells like fibroblasts.This method is based on the removal of the extrahepatic ducts and gallbladder, followed by meticulous dissection and scraping to remove fat and fibroblast layers. Structures are embedded in thick layers of collagen and cultured for approximately 3 weeks to allow outgrowth of cholangiocytes in monolayers, which can then be trypsinized and re plated for experimental use. 相似文献
36.
37.
Lin Jiang Fei Zhang Mao‐Lan Li Xu‐An Wang Yun‐Peng Jin Yi‐Jian Zhang Wei Lu Wen‐Guang Wu Yi‐Jun Shu Hao Weng Yang Cao Run‐Fa Bao Hai‐Bin Liang Zheng Wang Yi‐Chi Zhang Wei Gong Lei Zheng Shu‐Han Sun Ying‐Bin Liu 《EMBO reports》2017,18(10):1837-1853
Long noncoding RNAs (lncRNAs) play roles in the development and progression of many cancers; however, the contributions of lncRNAs to human gallbladder cancer (GBC) remain largely unknown. In this study, we identify a group of differentially expressed lncRNAs in human GBC tissues, including prognosis‐associated gallbladder cancer lncRNA (lncRNA‐PAGBC), which we find to be an independent prognostic marker in GBC. Functional analysis indicates that lncRNA‐PAGBC promotes tumour growth and metastasis of GBC cells. More importantly, as a competitive endogenous RNA (ceRNA), lncRNA‐PAGBC competitively binds to the tumour suppressive microRNAs miR‐133b and miR‐511. This competitive role of lncRNA‐PAGBC is required for its ability to promote tumour growth and metastasis and to activate the AKT/mTOR pathway. Moreover, lncRNA‐PAGBC interacts with polyadenylate binding protein cytoplasmic 1 (PABPC1) and is stabilized by this interaction. This work provides novel insight on the molecular pathogenesis of GBC. 相似文献
38.
Karl-Uwe Petersen John R. Wood Gerhard Schulze Konrad Heintze 《The Journal of membrane biology》1981,62(3):183-193
Summary Gallbladder fluid and electrolyte transport was investigatedin vitro. In guinea pig gallbladder, equimolar substitution of acetate, propionate, butyrate or valerate for HCO3 was increasingly effective in stimulating fluid absorption. The stimulatory potency of these compounds was a function of their chloroform water partition coefficients. The stimulatory effects of the isomers isobutyrate and isovalerate were less than predicted from their partition coefficients. Acidification of the gallbladder lumen, however, was strictly dependent on the partition coefficients for all of the above fatty acids. Unidirectional22Na fluxes were measured in rabbit and guinea pig gallbladders under short-circuit conditions. In the presence of butyrate stimulation of net Na flux was due entirely to an increase in the mucosal-to-serosal Na flux. Stimulation by butyrate was abolished by its omission from the mucosal bathing solution. The transepithelial electrical potential difference in both rabbit and guinea pig gallbladder became more lumen positive following mucosal but not serosal addition of butyrate. Net14C-butyrate fluxes were too small to account for stimulation of Na absorption in either species. Butyrate stimulation of Na absorption by guinea pig gallbladder was abolished by increasing the bathing pH from 7.4 to 8.1. Tris buffer (25mm) partially inhibited butyrate-dependent gallbladder fluid absorption by rabbit and guinea pig at pH 6.4 and 7.0, respectively, and completely at pH 8.4. These results reveal a marked similarity between butyrate and HCO3 stimulation of gallbladder NaCl and fluid absorption. The results are best explained by a double ion-exchange model, in which butyrate (HCO3) in the mucosal solution acts to maintain the intracellular supply of H+ and butyrate (HCO3) for countertransport of Na and Cl, respectively. 相似文献
39.
This study investigates the involvement of capacitative Ca2+ entry in excitation-contraction coupling in guinea pig gallbladder smooth muscle. Thapsigargin (0.1 nM-1 microM, a sarcoplasmic reticulum Ca(2+)-ATPase inhibitor) produced slowly developing sustained tonic contractions in guinea pig isolated gallbladder strips. All contractions approached 50% of the response to carbachol (10 microM) after 55 min. Contractile responses to thapsigargin (1 microM) were abolished in a Ca(2+)-free medium. Subsequent re-addition of Ca2+ (2.5 mM) produced a sustained tonic contraction (99 +/- 6% of the carbachol response). The contractile response to Ca2+ re-addition following incubation of tissues in a Ca(2+)-free bathing solution in the absence of thapsigargin was significantly less than in its presence (79 +/- 4 % vs 100 +/- 7 % of carbachol; p < 0.05). Contractile responses to Ca2+ re-addition following treatment with thapsigargin were attenuated by (a) the L-type voltage-operated Ca2+ channel antagonist, nifedipine (10 microM) and (b) the general inhibitor of Ca2+ entry channels including store-operated channels, SK&F96365 (50 microM and 100 microM). In separate experiments, responses to Ca2+ re-addition were essentially abolished by the tyrosine kinase inhibitor, genistein (100 microM). These results suggest that capacitative Ca2+ entry provides a source of activator Ca2+ for guinea pig gallbladder smooth muscle contraction. Contractile responses to Ca2+ re-addition following depletion of sarcoplasmic reticulum Ca2+ stores with thapsigargin, are mediated in part by Ca2+ entry through voltage-operated Ca2+ channels and by capacitative Ca2+ entry through store-operated Ca2+ channels which can be blocked by SK&F96365. Furthermore, capacitative Ca2+ entry in this tissue may be modulated by tyrosine kinase. 相似文献
40.
Summary The transepithelial fluxes, conductances and permeabilities of Li+, Na+, K+, Cs+, NH
4
+
and H3CNH
3
+
were studied under ionic concentrations ranging from 12 to 250mm inBufo arenarum gallbladders. When these measurements are carefully corrected in order to get only the component due to the paracellular cation channels, the following results are obtained: (1) The permeability ratios (cationic/anionic) are a decreasing function of salt concentration. (2) The partial conductances through paracellular cationic channels show nonlinear saturable concentration kinetics. (3) Moreover, partial conductance kinetics of K+, Cs+ and NH
4
+
present a maximum followed, at higher concentratons, by a negative-slope region. (4) The selectivity sequences obtained from biionic potentials do not agree with those obtained from partial conductance measurements. (5) The unidirectional22Na tracer flux (serosal to mucosal) is inhibited by 63% when the K+ symmetrical concentration in the bathing solutions is raised from 25 to 200mm. (6) When the unidirectional42K fluxes (serosal to mucosal) at 200mm KCl Na-free solutions are compared with K+ partial conductance by means of the Hodgkin and Keynes (Hodgkin, A.L., Keynes, R.D. 1955.J. Physiol London
128:61–88) expression, then factor is 2.0. These results indicate that cations do not follow the independence principle and behave as in single-file diffusion multi-ion pores when crossing the paracellular cation channels ofBufo arenarum gallbladder epithelium. 相似文献