peerj_json_files/PeerJ_Json_102.json

{
    "v1_Abstract": "Background /Aim: Significant physiological changes occur during pregnancy and lactation. Intrahepatic cholestasis of pregnancy (ICP) is a liver disease closely related to disruption of bile acid homeostasis. The objective of this study was to examine the regulation of bile acid synthesis and transport in normal pregnant and lactating rats. Materials and Methods: Livers from timed pregnant SD rats were collected on gestational days (GD) 10, 14 and 19, and postnatal days (PND) 1,7,14 and 21. Total bile acids were determined by the enzymatic method, total RNA was isolated and subjected to real time RT-PCR analysis. Liver protein was extracted for western-blot analysis. Results: Under physiological conditions hepatic bile acids were not elevated during pregnancy but increased during lactation in rats. Bile acid synthesis rate-limiting enzyme Cyp7a1 was unchanged in gestations days, but increased on PND14 and21 at mRNA and protein levels. Expression of Cyp8b1, Cyp27a1 and Cyp7b1 was also higher during lactation. The mRNA levels of small heterodimer partner (SHP) and protein levels of farnesoid X receptor (FXR) were increased during pregnancy and lactation. Bile acid transporters Ntcp, Bsep, Mrp3 and Mrp4 were lower at gestation, but increased during lactation. Hepatic Oatp transporters were decreased during pregnancy and lactation. Conclusion: Hepatic bile acid homeostasis is maintained during normal pregnancy in rats, probably through the FXR-SHP regulation. The expression of bile acid synthesis genes and liver bile acid accumulation were increased during lactation, together with increased expression of bile acid efflux transporter Bsep, Mrp3 and Mrp4.",
    "v2_Abstract": "Background /Aim: Significant physiological changes occur during pregnancy and lactation. Intrahepatic cholestasis of pregnancy (ICP) is a liver disease closely related to disruption of bile acid homeostasis. The objective of this study was to examine the regulation of bile acid synthesis and transport in normal pregnant and lactation rats. Materials and Methods: Livers from timely pregnant SD rats were collected on gestational days (GD) 10, 14 and 19, and postnatal days (PND) 1,7,14 and 21. Total bile acids were determined by the enzymatic method, total RNA was isolated and subjected to real time RT-PCR analysis. Liver protein was extracted for western-blot analysis. Results: Under physiological conditions hepatic bile acids were not elevated during pregnancy but increased during lactation in rats. Bile acid synthesis rate-limiting enzyme Cyp7a1 was unchanged in gestations days, but increased on PND14 and21 at mRNA and protein levels. Expression of Cyp8b1, Cyp27a1 and Cyp7b1 was also higher during lactation. The mRNA levels of small heterodimer partner (SHP) and protein levels of farnesoid X receptor (FXR) were increased during pregnancy and lactation. Bile acid transporters Ntcp, Bsep, Mrp3 and Mrp4 were lower at gestation, but increased during lactation. Hepatic Oatp transporters were decreased during pregnancy and lactation. Conclusion: Hepatic bile acid homeostasis is maintained during normal pregnancy in rats, probably through the FXR-SHP regulation. The expression of bile acid synthesis genes and liver bile acid accumulation were increased during lactation, together with increased expression of bile acid efflux transporter Bsep, Mrp3 and Mrp4.",
    "v3_Abstract": "Background /Aim: Intrahepatic cholestasis of pregnancy (ICP) is a liver disease which may occur in the third trimester of pregnancy. The etiology and pathogenesis of ICP is thought to be closely related to bile acid metabolism. The objective of this study was to examine the regulation of bile acid metabolism during normal pregnant and lactation in rats. Materials and Methods: Livers from timely pregnant SD rats were collected on gestational days (GD) 10, 14 and 19, and postnatal days (PND) 1,7,14 and 21. Total bile acids were determined by the enzymatic method, total RNA was isolated and subjected to real time RT-PCR analysis. Liver protein was extracted for western-blot analysis. Results: Under physiological conditions hepatic bile acids were not elevated during pregnancy but increased during lactation in rats. Bile acid synthesis rate-limiting enzyme Cyp7a1 was unchanged in gestations days, but increased on PND14 and21 at mRNA and protein levels. Expression of Cyp8b1, Cyp27a1 and Cyp7b1 was also higher during lactation. The expression of small heterodimer partner (SHP) was increased at GD19 and lactation days, and farnesoid X receptor (FXR) increased on postpartum. Bile acid transporters Ntcp, Bsep, Mrp3 and Mrp4 were lower at gestation, but increased during lactation. Hepatic Oatp transporters were decreased during pregnancy and lactation. Conclusion: Hepatic bile acid homeostasis maintained during normal pregnancy in rats, probably through the regulation of SHP. The expression of bile acid synthesis genes and liver bile acids were increased during lactation, together with increased expression of bile acid transporters.",
    "v1_text": "expression of nuclear receptors : PeerJ reviewing PDF | (v2013:06:607:2:0:NEW 3 Aug 2013) R ev ie w in g M an us cr ip t PeerJ reviewing PDF | (v2013:06:607:2:0:NEW 3 Aug 2013) R ev ie w in g M an us cr ip t Figure 5 Fig. 5 fig : Liver bile acid concentrations PeerJ reviewing PDF | (v2013:06:607:2:0:NEW 3 Aug 2013) R ev ie w in g M an us cr ip t PeerJ reviewing PDF | (v2013:06:607:2:0:NEW 3 Aug 2013) R ev ie w in g M an us cr ip t Figure 2 Fig. 2 Bile acid synthesis gene expression PeerJ reviewing PDF | (v2013:06:607:2:0:NEW 3 Aug 2013) R ev ie w in g M an us cr ip t PeerJ reviewing PDF | (v2013:06:607:2:0:NEW 3 Aug 2013) R ev ie w in g M an us cr ip t Figure 3 Hepatic expression of bile acid synthesis rate-limiting protein CYP7A1 in pregnant and lactating rat. Western bolts were performed using liver homogenates from control, pregnant rats in GD 10, 14, 19 and PND 1, 7, 14 and 21. The expression of CYP7A1 was semi-quantified by band intensity.Values are mean \u00b1 SEM. Dark gray bars represent pregnant rat, and black bars represent lactating rat. Significant difference was confirmed by two-tailed independent Samples test method (P<0.05). PeerJ reviewing PDF | (v2013:06:607:2:0:NEW 3 Aug 2013) R ev ie w in g M an us cr ip t PeerJ reviewing PDF | (v2013:06:607:2:0:NEW 3 Aug 2013) R ev ie w in g M an us cr ip t Figure 4 Fig. 4 fxr protein expression : PeerJ reviewing PDF | (v2013:06:607:2:0:NEW 3 Aug 2013) R ev ie w in g M an us cr ip t PeerJ reviewing PDF | (v2013:06:607:2:0:NEW 3 Aug 2013) R ev ie w in g M an us cr ip t Figure 6 Fig. 6 efflux transporters : PeerJ reviewing PDF | (v2013:06:607:2:0:NEW 3 Aug 2013) R ev ie w in g M an us cr ip t PeerJ reviewing PDF | (v2013:06:607:2:0:NEW 3 Aug 2013) R ev ie w in g M an us cr ip t Figure 7 Fig. 7 uptake transporter expression : PeerJ reviewing PDF | (v2013:06:607:2:0:NEW 3 Aug 2013) R ev ie w in g M an us cr ip t PeerJ reviewing PDF | (v2013:06:607:2:0:NEW 3 Aug 2013) R ev ie w in g M an us cr ip t",
    "v2_text": "expression of nuclear receptors : PeerJ reviewing PDF | (v2013:06:607:1:1:REVIEW 27 Jul 2013) R ev ie w in g M an us cr ip t PeerJ reviewing PDF | (v2013:06:607:1:1:REVIEW 27 Jul 2013) R ev ie w in g M an us cr ip t Figure 5 Fig. 5 fig : Liver bile acid concentrations PeerJ reviewing PDF | (v2013:06:607:1:1:REVIEW 27 Jul 2013) R ev ie w in g M an us cr ip t PeerJ reviewing PDF | (v2013:06:607:1:1:REVIEW 27 Jul 2013) R ev ie w in g M an us cr ip t Figure 2 Fig. 2 Bile acid synthesis gene expression PeerJ reviewing PDF | (v2013:06:607:1:1:REVIEW 27 Jul 2013) R ev ie w in g M an us cr ip t PeerJ reviewing PDF | (v2013:06:607:1:1:REVIEW 27 Jul 2013) R ev ie w in g M an us cr ip t Figure 3 Hepatic expression of bile acid synthesis rate-limiting protein CYP7A1 in pregnant and lactating rat. Western bolts were performed using liver homogenates from control, pregnant rats in GD 10, 14, 19 and PND 1, 7, 14 and 21. The expression of CYP7A1 was semi-quantified by band intensity.Values are mean \u00b1 SEM. Dark gray bars represent pregnant rat, and black bars represent lactating rat. Significant difference was confirmed by two-tailed independent Samples test method (P<0.05). PeerJ reviewing PDF | (v2013:06:607:1:1:REVIEW 27 Jul 2013) R ev ie w in g M an us cr ip t PeerJ reviewing PDF | (v2013:06:607:1:1:REVIEW 27 Jul 2013) R ev ie w in g M an us cr ip t Figure 4 Fig. 4 fxr protein expression : PeerJ reviewing PDF | (v2013:06:607:1:1:REVIEW 27 Jul 2013) R ev ie w in g M an us cr ip t PeerJ reviewing PDF | (v2013:06:607:1:1:REVIEW 27 Jul 2013) R ev ie w in g M an us cr ip t Figure 6 Fig. 6 efflux transporters : PeerJ reviewing PDF | (v2013:06:607:1:1:REVIEW 27 Jul 2013) R ev ie w in g M an us cr ip t PeerJ reviewing PDF | (v2013:06:607:1:1:REVIEW 27 Jul 2013) R ev ie w in g M an us cr ip t Figure 7 Fig. 7 uptake transporter expression : PeerJ reviewing PDF | (v2013:06:607:1:1:REVIEW 27 Jul 2013) R ev ie w in g M an us cr ip t PeerJ reviewing PDF | (v2013:06:607:1:1:REVIEW 27 Jul 2013) R ev ie w in g M an us cr ip t",
    "url": "https://peerj.com/articles/144/reviews/",
    "review_1": "Santosh Patnaik \u00b7 Aug 6, 2013 \u00b7 Academic Editor\nACCEPT\nThe issues raised in the last round of review have bee adequately addressed.",
    "review_2": "Santosh Patnaik \u00b7 Jul 19, 2013 \u00b7 Academic Editor\nMINOR REVISIONS\nThe manuscript that you submitted is prepared very well, with a clear, succinct and consistently styled presentation, appropriate discourse, details and references, and suitably composed figures.\n\nOf the three reviewers, only one has suggested a few changes, all of which are minor. The comment about mentioning the phenomenon of caspase-independent cytotoxic effect of docetaxel on prostate cancer cells is relatively important and should be addressed. Regarding the comments asking whether Coomassie stain was used on protein blots or gels, and whether the LNCaP and PC3 cells that were used in the study were parental or derived, please clarify appropriately in the manuscript as other readers of the publication may have the same questions. You can choose to address the remaining comments of the reviewer at your discretion.",
    "review_3": "Reviewer 1 \u00b7 Jul 18, 2013\nBasic reporting\nThe majority of the manuscript is coherent, simplistic and intriguing.\nHowever, the 4th paragraph of the introduction could use a little more clarification and purpose. Lines 317-320 would fit well into this paragraph.\n\nIt needs to be mentioned in the introduction or Discussion section that docetaxel induced prostate cancer death involves concomintant activation of both caspase- and lysosome-dependent pathways (Mediavilla-Varela M. et al., Mol. Cancer. 2009)\nExperimental design\nIt is stated that ABT-737 can sensitize androgen-dependent LNCAP and PC-3 cells to docetaxel and 1198. Are both these cell lines docetaxel-resistant versions of the parental cells or are they docetaxel sensitive LNCAP and PC-3 cells?\n\nMaterials and Methods- ATCC recommends growing PC-3 cells in medium with 10% FBS.\n\nIf selection of a loading control is difficult, it is better to use Ponceaus staining of the membrane rather than Coomassie blue staining of the gel because it is the same membrane and is ideal for monitoring transfer. However, some researchers are using a new technique of protein staining with Coomassie that can be used on the membrane after immunodetection (Welinder and Ekblad, J. Proteome Res. 2011). Please clarify if you stained the gel or membrane.\nValidity of the findings\nNo comments\nAdditional comments\nI would suggest uniformity in the labeling of figures such as Figures 1A and 1B. I would choose between LN or L for LNCaP and DU or D for DU145. Also, I would not use PC in labeling for PC3 cells as PC has been consistently used in the rest of the paper as an acronym for prostate cancer. I would suggest identifying prostate cancer as PCa to avoid this confusion.\nCite this review as\nAnonymous Reviewer (2013) Peer Review #1 of \"ABT-737, a small molecule Bcl-2/Bcl-xL antagonist, increases antimitotic-mediated apoptosis in human prostate cancer cells (v0.1)\". PeerJ https://doi.org/10.7287/peerj.144v0.1/reviews/1",
    "review_4": "Reviewer 2 \u00b7 Jul 16, 2013\nBasic reporting\nNo comments.\nExperimental design\nThis was actually very well done; the results of this manuscript appear to be the collaborative work of several different projects, which, as described in the methods section of this paper, appear to be technically sound.\nValidity of the findings\nThe results of the author's experiments is clearly conveyed in the context of what is known in the general literature. Their final conclusions appear to be supported by their findings in the results.\nAdditional comments\nThis was an interesting investigation into some of the biologic mechanisms for chemotherapeutic resistance in the setting of Castration resistant prostate cancer with well-designed experiments to quantify the relative importance of roles played by certain pro/anti-apoptotic proteins. It appears that the scientific methods discussed and conclusions derived from this set of studies were well-designed and appropriate, respectively.\nCite this review as\nAnonymous Reviewer (2013) Peer Review #2 of \"ABT-737, a small molecule Bcl-2/Bcl-xL antagonist, increases antimitotic-mediated apoptosis in human prostate cancer cells (v0.1)\". PeerJ https://doi.org/10.7287/peerj.144v0.1/reviews/2",
    "pdf_1": "https://peerj.com/articles/144v0.2/submission",
    "pdf_2": "https://peerj.com/articles/144v0.1/submission",
    "review_5": "Reviewer 3 \u00b7 Jun 29, 2013\nBasic reporting\nThe article is well written and conforms to the PeerJ policies.\nExperimental design\nThe experimental design is appropriate for the authors to make their conclusions.\nValidity of the findings\nThe data is sound albeit not incredibly novel or surprising. I reviewed this manuscript for a different journal and that was the main conclusion of the reviews. Thus if impact is not a factor in the decision, I believe this is an acceptable paper.\nAdditional comments\nThis is an interesting finding. The experiments are well-performed, however the findings and conclusions are not terribly surprising. So the study is not incredibly novel, but it is solid and appropriate.\nCite this review as\nAnonymous Reviewer (2013) Peer Review #3 of \"ABT-737, a small molecule Bcl-2/Bcl-xL antagonist, increases antimitotic-mediated apoptosis in human prostate cancer cells (v0.1)\". PeerJ https://doi.org/10.7287/peerj.144v0.1/reviews/3",
    "all_reviews": "Review 1: Santosh Patnaik \u00b7 Aug 6, 2013 \u00b7 Academic Editor\nACCEPT\nThe issues raised in the last round of review have bee adequately addressed.\nReview 2: Santosh Patnaik \u00b7 Jul 19, 2013 \u00b7 Academic Editor\nMINOR REVISIONS\nThe manuscript that you submitted is prepared very well, with a clear, succinct and consistently styled presentation, appropriate discourse, details and references, and suitably composed figures.\n\nOf the three reviewers, only one has suggested a few changes, all of which are minor. The comment about mentioning the phenomenon of caspase-independent cytotoxic effect of docetaxel on prostate cancer cells is relatively important and should be addressed. Regarding the comments asking whether Coomassie stain was used on protein blots or gels, and whether the LNCaP and PC3 cells that were used in the study were parental or derived, please clarify appropriately in the manuscript as other readers of the publication may have the same questions. You can choose to address the remaining comments of the reviewer at your discretion.\nReview 3: Reviewer 1 \u00b7 Jul 18, 2013\nBasic reporting\nThe majority of the manuscript is coherent, simplistic and intriguing.\nHowever, the 4th paragraph of the introduction could use a little more clarification and purpose. Lines 317-320 would fit well into this paragraph.\n\nIt needs to be mentioned in the introduction or Discussion section that docetaxel induced prostate cancer death involves concomintant activation of both caspase- and lysosome-dependent pathways (Mediavilla-Varela M. et al., Mol. Cancer. 2009)\nExperimental design\nIt is stated that ABT-737 can sensitize androgen-dependent LNCAP and PC-3 cells to docetaxel and 1198. Are both these cell lines docetaxel-resistant versions of the parental cells or are they docetaxel sensitive LNCAP and PC-3 cells?\n\nMaterials and Methods- ATCC recommends growing PC-3 cells in medium with 10% FBS.\n\nIf selection of a loading control is difficult, it is better to use Ponceaus staining of the membrane rather than Coomassie blue staining of the gel because it is the same membrane and is ideal for monitoring transfer. However, some researchers are using a new technique of protein staining with Coomassie that can be used on the membrane after immunodetection (Welinder and Ekblad, J. Proteome Res. 2011). Please clarify if you stained the gel or membrane.\nValidity of the findings\nNo comments\nAdditional comments\nI would suggest uniformity in the labeling of figures such as Figures 1A and 1B. I would choose between LN or L for LNCaP and DU or D for DU145. Also, I would not use PC in labeling for PC3 cells as PC has been consistently used in the rest of the paper as an acronym for prostate cancer. I would suggest identifying prostate cancer as PCa to avoid this confusion.\nCite this review as\nAnonymous Reviewer (2013) Peer Review #1 of \"ABT-737, a small molecule Bcl-2/Bcl-xL antagonist, increases antimitotic-mediated apoptosis in human prostate cancer cells (v0.1)\". PeerJ https://doi.org/10.7287/peerj.144v0.1/reviews/1\nReview 4: Reviewer 2 \u00b7 Jul 16, 2013\nBasic reporting\nNo comments.\nExperimental design\nThis was actually very well done; the results of this manuscript appear to be the collaborative work of several different projects, which, as described in the methods section of this paper, appear to be technically sound.\nValidity of the findings\nThe results of the author's experiments is clearly conveyed in the context of what is known in the general literature. Their final conclusions appear to be supported by their findings in the results.\nAdditional comments\nThis was an interesting investigation into some of the biologic mechanisms for chemotherapeutic resistance in the setting of Castration resistant prostate cancer with well-designed experiments to quantify the relative importance of roles played by certain pro/anti-apoptotic proteins. It appears that the scientific methods discussed and conclusions derived from this set of studies were well-designed and appropriate, respectively.\nCite this review as\nAnonymous Reviewer (2013) Peer Review #2 of \"ABT-737, a small molecule Bcl-2/Bcl-xL antagonist, increases antimitotic-mediated apoptosis in human prostate cancer cells (v0.1)\". PeerJ https://doi.org/10.7287/peerj.144v0.1/reviews/2\nReview 5: Reviewer 3 \u00b7 Jun 29, 2013\nBasic reporting\nThe article is well written and conforms to the PeerJ policies.\nExperimental design\nThe experimental design is appropriate for the authors to make their conclusions.\nValidity of the findings\nThe data is sound albeit not incredibly novel or surprising. I reviewed this manuscript for a different journal and that was the main conclusion of the reviews. Thus if impact is not a factor in the decision, I believe this is an acceptable paper.\nAdditional comments\nThis is an interesting finding. The experiments are well-performed, however the findings and conclusions are not terribly surprising. So the study is not incredibly novel, but it is solid and appropriate.\nCite this review as\nAnonymous Reviewer (2013) Peer Review #3 of \"ABT-737, a small molecule Bcl-2/Bcl-xL antagonist, increases antimitotic-mediated apoptosis in human prostate cancer cells (v0.1)\". PeerJ https://doi.org/10.7287/peerj.144v0.1/reviews/3\nReview 6: \n",
    "LLM_extracted_review": "['Review 1: The issues raised in the last round of review have been adequately addressed.\\n\\nReview 2: The manuscript is prepared very well, with a clear, succinct and consistently styled presentation, appropriate discourse, details and references, and suitably composed figures. Only one reviewer suggested a few minor changes. The comment about mentioning the phenomenon of caspase-independent cytotoxic effect of docetaxel on prostate cancer cells is relatively important and should be addressed. Clarification is needed regarding whether Coomassie stain was used on protein blots or gels, and whether the LNCaP and PC3 cells used in the study were parental or derived.\\n\\nReview 3: The majority of the manuscript is coherent, simplistic and intriguing. However, the 4th paragraph of the introduction could use a little more clarification and purpose. It needs to be mentioned that docetaxel induced prostate cancer death involves concomitant activation of both caspase- and lysosome-dependent pathways. Clarification is needed on whether the LNCAP and PC-3 cells are docetaxel-resistant or sensitive. It is better to use Ponceaus staining of the membrane rather than Coomassie blue staining of the gel. Uniformity in the labeling of figures is suggested to avoid confusion.\\n\\nReview 4: The experimental design is very well done; the results appear to be the collaborative work of several different projects and are technically sound. The results are clearly conveyed in the context of existing literature, and the conclusions appear to be supported by the findings. The investigation into the biologic mechanisms for chemotherapeutic resistance is interesting, with well-designed experiments.\\n\\nReview 5: The article is well written and conforms to PeerJ policies. The experimental design is appropriate for the conclusions made. The data is sound but not incredibly novel or surprising. The study is solid and appropriate, though the findings and conclusions are not terribly surprising.']"
}