Title: Vitamin D3/VDR alleviates double-stranded RNA virus -induced biliary epithelial cell
damage by inhibiting autophagy
Version: 5 Date: 07 Dec 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors , please address the following points below
-While the findings from the mouse model and retrospective clinical data are promising, there
is a notable lack of discussion regarding the challenges associated with translating these results
into clinical practice. For instance, the long-term effects of vitamin D receptor (VDR) activation
on other immune or metabolic pathways in patients with biliary atresia (BA) remain uncertain. A
comprehensive exploration of dosage, treatment duration, and safety profiles would significantly
enhance the clinical implications of these findings.
-The retrospective clinical analysis only offers a correlation between calcitriol treatment and
improved outcomes. To establish causality and accurately assess the efficacy of VDR activators
in BA, it is essential to conduct a prospective randomized controlled trial (RCT).
-Moreover, it would be advantageous to provide a detailed examination of how autophagy
inhibition specifically benefits bile duct epithelial cells (BECs) and whether long-term
suppression of autophagy could result in any adverse consequences.
-The study does not adequately address the potential off-target effects of chloroquine, nor does
it consider whether its inhibition of autophagy might lead to unintended consequences in other
cell types or organs. Furthermore, there is insufficient exploration of potential interactions with
other immune or inflammatory pathways that may influence clinical outcomes.
-A more thorough analysis of how the autophagic process in BA differs from that in conditions
such as alcoholic liver disease or cirrhosis would clarify the proposed therapeutic strategy.
Additionally, the relationship between SRC activation and the ERK1/2 pathway in the context
of BA warrants further investigation.
-Incorporating extended follow-up periods in animal models to evaluate the long-term benefits
of VDR activation would bolster the rationale for its therapeutic application in BA. ---Overall,
while this approach represents a novel strategy for addressing virus-induced BA—specifically
through the modulation of autophagy and inflammation in bile duct epithelial cells—further
validation in larger clinical cohorts and more diverse BA models is essential to establish the
clinical utility of VDR-based therapies.
Title: Vitamin D3/VDR alleviates double-stranded RNA virus -induced biliary epithelial cell
damage by inhibiting autophagy
Version: 5 Date: 07 Dec 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors , please address the following points below
-While the findings from the mouse model and retrospective clinical data are promising, there
is a notable lack of discussion regarding the challenges associated with translating these results
into clinical practice. For instance, the long-term effects of vitamin D receptor (VDR) activation
on other immune or metabolic pathways in patients with biliary atresia (BA) remain uncertain. A
comprehensive exploration of dosage, treatment duration, and safety profiles would significantly
enhance the clinical implications of these findings.
-The retrospective clinical analysis only offers a correlation between calcitriol treatment and
improved outcomes. To establish causality and accurately assess the efficacy of VDR activators
in BA, it is essential to conduct a prospective randomized controlled trial (RCT).
-Moreover, it would be advantageous to provide a detailed examination of how autophagy
inhibition specifically benefits bile duct epithelial cells (BECs) and whether long-term
suppression of autophagy could result in any adverse consequences.
-The study does not adequately address the potential off-target effects of chloroquine, nor does
it consider whether its inhibition of autophagy might lead to unintended consequences in other
cell types or organs. Furthermore, there is insufficient exploration of potential interactions with
other immune or inflammatory pathways that may influence clinical outcomes.
-A more thorough analysis of how the autophagic process in BA differs from that in conditions
such as alcoholic liver disease or cirrhosis would clarify the proposed therapeutic strategy.
Additionally, the relationship between SRC activation and the ERK1/2 pathway in the context
of BA warrants further investigation.
-Incorporating extended follow-up periods in animal models to evaluate the long-term benefits
of VDR activation would bolster the rationale for its therapeutic application in BA. ---Overall,
while this approach represents a novel strategy for addressing virus-induced BA—specifically
through the modulation of autophagy and inflammation in bile duct epithelial cells—further
validation in larger clinical cohorts and more diverse BA models is essential to establish the
clinical utility of VDR-based therapies.
Please review this paper.
user
Title: Vitamin D3/VDR alleviates double-stranded RNA virus -induced biliary epithelial cell
damage by inhibiting autophagy
Version: 5 Date: 07 Dec 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors , please address the following points below
-While the findings from the mouse model and retrospective clinical data are promising, there
is a notable lack of discussion regarding the challenges associated with translating these results
into clinical practice. For instance, the long-term effects of vitamin D receptor (VDR) activation
on other immune or metabolic pathways in patients with biliary atresia (BA) remain uncertain. A
comprehensive exploration of dosage, treatment duration, and safety profiles would significantly
enhance the clinical implications of these findings.
-The retrospective clinical analysis only offers a correlation between calcitriol treatment and
improved outcomes. To establish causality and accurately assess the efficacy of VDR activators
in BA, it is essential to conduct a prospective randomized controlled trial (RCT).
-Moreover, it would be advantageous to provide a detailed examination of how autophagy
inhibition specifically benefits bile duct epithelial cells (BECs) and whether long-term
suppression of autophagy could result in any adverse consequences.
-The study does not adequately address the potential off-target effects of chloroquine, nor does
it consider whether its inhibition of autophagy might lead to unintended consequences in other
cell types or organs. Furthermore, there is insufficient exploration of potential interactions with
other immune or inflammatory pathways that may influence clinical outcomes.
-A more thorough analysis of how the autophagic process in BA differs from that in conditions
such as alcoholic liver disease or cirrhosis would clarify the proposed therapeutic strategy.
Additionally, the relationship between SRC activation and the ERK1/2 pathway in the context
of BA warrants further investigation.
-Incorporating extended follow-up periods in animal models to evaluate the long-term benefits
of VDR activation would bolster the rationale for its therapeutic application in BA. ---Overall,
while this approach represents a novel strategy for addressing virus-induced BA—specifically
through the modulation of autophagy and inflammation in bile duct epithelial cells—further
validation in larger clinical cohorts and more diverse BA models is essential to establish the
clinical utility of VDR-based therapies.
assistant