Bufalin suppresses endometriosis progression by inducing pyroptosis and apoptosis
Open accessAbstract
The steroid receptor coactivator (SRC)-1 isoform/estrogen receptor (ER)-β axis has an essential role in endometriosis progression. In this context, therefore, bufalin was employed as a ‘tool compound’ to evaluate inhibitors of SRC in alternative endometriosis treatment. Bufalin effectively suppressed the growth of primary human endometrial stroma cells isolated from endometriosis patients compared to women without endometriosis and immortalized human endometrial epithelial and stromal cells expressing the SRC-1 isoform compared to their parental cells in vitro . In vivo , compared to the vehicle, bufalin treatment significantly suppressed the growth of endometriotic lesions in mice with surgically induced endometriosis because bufalin disrupted the functional axis of SRC-1 isoform/ERβ by increasing SRC-1 isoform protein stability, hyperactivating the transcriptional activity of the SRC-1 isoform and degrading the ERβ protein by proteasome 26S subunit, non-ATPase 2 in endometriotic lesions. Bufalin treatment elevated the apoptosis signaling in epithelial cells of endometriotic lesions. In stromal cells of endometriotic lesions, bufalin treatment increased the levels of pyroptosis markers (caspase 1 and the active form of interleukin 1β) and reduced proliferation. In addition, bufalin treatment increased the expression levels of endoplasmic reticulum-stress (ERS) markers (PKR-like ER kinase, protein disulfide isomerase and binding immunoglobulin) in endometriotic lesions. Collectively, the bufalin-induced disruption of the SRC-1 isoform/ERβ axis might induce apoptosis, pyroptosis and ERS signaling in endometriotic lesions, causing the suppression of endometriosis. Therefore, future generations of SRC-modulators could be employed as an alternative medical approach for endometriosis treatment.
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- Findingown data
In IHESCs, 20 nM bufalin for 48 hours reduced full-length SRC-1 levels by 5.0-fold compared with vehicle.
“In contrast to the results for the SRC-1 isoform, 20 nM bufalin treatment, compared with the vehicle, reduced the levels of full-length SRC-1 by 5.0-fold in IHESCs with 48-hour treatment (Fig. 2D).”
Quote in the paperSubstantial claim - Findingown data
Bufalin inhibited the growth of primary human endometrial stromal cells from endometriosis patients more than those from women without endometriosis.
“Bufalin effectively inhibited the growth of primary human endometrial stromal cells from endometriosis patients compared to those isolated from women without endometriosis (Fig. 1A).”
- Also stated in: § Abstract · plain
“Bufalin effectively suppressed the growth of primary human endometrial stroma cells isolated from endometriosis patients compared to women without endometriosis and immortalized human endometrial epithelial and stromal cells expressing the SRC-1 isoform compared to their parental cells in vitro.”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Findingown data
In IHESCs:SRC-1 ISO, 20 nM bufalin for 48 hours elevated SRC-1 isoform protein levels by 2.4-fold compared with vehicle.
“We found that 20 nM bufalin treatment, compared with the vehicle, elevated the SRC-1 isoform protein levels by 2.4-fold in IHESCs:SRC-1 ISO with 48-hour treatment (Fig. 2C).”
Quote in the paperSubstantial claim - Findingown data
Bufalin significantly reduced the growth of IHESCs and IHEECs overexpressing the SRC-1 isoform compared with their parental cells.
“The growth of IHESCs:SRC-1 ISO and IHEECS:SRC-1 ISO was significantly reduced by bufalin treatment compared to their parental cells (Figs. 1B and 1C).”
Quote in the paperSubstantial claim - Findingown data
Bufalin treatment increased SRC-1 isoform protein levels by 2.7-fold (p=0.005) in endometriotic lesions compared with vehicle.
“Western blot analysis revealed that compared to the vehicle, bufalin treatment increased SRC-1 isoform protein levels by 2.7-fold (p=0.005) in endometriotic lesions (Fig. 2B).”
Quote in the paperSubstantial claim
- Findingown data
In mice with surgically induced endometriosis, bufalin treatment reduced endometriotic lesion volume by 14-fold compared with vehicle (p=0.009).
“Compared to the vehicle, bufalin treatment reduced the volume of the endometriotic lesions by 14-fold (p=0.009) (Fig. 2A).”
- Also stated in: § Abstract · plain
“In vivo, compared to the vehicle, bufalin treatment significantly suppressed the growth of endometriotic lesions in mice with surgically induced endometriosis”
Quote in the paperSubstantial claim- Rests on an assumption: The surgically induced mouse model of endometriosis is representative of human endometriosis for evaluating bufalin's effects.
- Also stated in: § Abstract · plain
- Findingown data
Estrogen treatment significantly increased the intrinsic transcriptional activity of ERβ compared with vehicle.
“Compared with the vehicle, estrogen treatment significantly enhanced the intrinsic transcriptional activity of ERβ (Fig. 3B).”
Quote in the paperNot a substantial claim - Findingcitation
PSMD2 and UBA7 specifically co-precipitated with ERβ from endometriotic lesions.
“these data revealed that several proteasome components, such as proteasome 26S Subunit, non-ATPase 2 (PSMD2) and ubiquitin-like modifier activating enzyme 7 (UBA7), were specifically co-precipitated with ERβ from endometriotic lesions.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Han et al. 2015
Not checked in the free run.
- Findingown data
The SRC-1 isoform possesses intrinsic transcriptional activity.
“Compared to the empty expression vector control, the SRC-1 isoform had an intrinsic transcriptional activity”
Quote in the paperNot a substantial claim - Findingown data
Bufalin treatment did not alter the E2-induced transcriptional activity of ERβ compared with vehicle.
“However, compared to the vehicle, bufalin treatment did not affect the E2-induced transcriptional activity of ERβ (Fig. 3B).”
Quote in the paperNot a substantial claim - Findingown data
Bufalin treatment reduced Ki-67 levels by 62.5% (P=0.0032) in the stromal compartment of endometriotic lesions compared with vehicle.
“bufalin reduced the levels of Ki-67 by 62.5% (P=0.0032) in the stromal compartment of endometriotic lesions compared to the vehicle (Fig. 5C).”
Quote in the paperSubstantial claim- Rests on an assumption: The surgically induced mouse model of endometriosis is representative of human endometriosis for evaluating bufalin's effects.
- Findingown data
Overexpression of PSMD2 reduced ERβ protein levels by 2.5-fold in HeLa cells compared with empty vector control.
“The overexpression of PSMD2 decreased ERβ protein levels by 2.5-fold in HeLa cells compared with the empty vector control (Fig. 4C).”
Quote in the paperSubstantial claim - Findingown data
Bufalin treatment raised the level of active caspase 3 by 9.8-fold (p=0.012) in epithelial cells from endometriotic lesions relative to vehicle.
“Bufalin treatment increased the levels of the active form of caspase 3 by 9.8-fold (p=0.012) in epithelial cells from endometriotic lesions compared to the vehicle (Fig. 5E).”
Quote in the paperSubstantial claim - Findingown data
Bufalin treatment did not significantly reduce proliferation in the epithelial compartment of endometriotic lesions.
“Proliferation in the epithelial compartment of endometriotic lesions was not significantly reduced by bufalin treatment (Fig. 5B).”
Quote in the paperNot a substantial claim- Rests on an assumption: The surgically induced mouse model of endometriosis is representative of human endometriosis for evaluating bufalin's effects.
- Findingown data
At 5 nM, bufalin increased the intrinsic transcriptional activity of the SRC-1 isoform by 3-fold (P=0.005) compared with vehicle.
“its transcriptional activity was elevated by 5 nM bufalin treatment (3-fold, P=0.005) compared to the vehicle (Fig. 3A).”
Quote in the paperSubstantial claim - Findingown data
Overexpression of UBA7 did not degrade ERβ protein compared with empty vector control.
“However, the overexpression of UBA7 protein did not degrade ERβ protein compared to the empty vector control (Fig. 4C).”
Quote in the paperSubstantial claim - Findingown data
Bufalin treatment reduced ERβ protein levels by 7.2-fold (p=0.01) in endometriotic lesions compared with vehicle.
“bufalin treatment, compared to the vehicle, reduced ERβ protein levels by 7.2-fold (p=0.01) in endometriotic lesions (Fig. 2B).”
Quote in the paperSubstantial claim - Findingown data
Bufalin treatment increased PSMD2 and UBA7 levels in both epithelial and stromal cells of endometriotic lesions compared with vehicle.
“Bufalin treatment increased the levels of PSMD2 and UBA7 in both epithelial and stromal cells from endometriotic lesions compared to vehicle-treated endometriotic lesions (Figs. 4A and 4B).”
Quote in the paperSubstantial claim- Rests on an assumption: The surgically induced mouse model of endometriosis is representative of human endometriosis for evaluating bufalin's effects.
- Findingown data
In IHESCs:SRC-1 ISO, 20 nM bufalin for 48 hours reduced ERβ levels by 5.0-fold compared with vehicle.
“ERβ levels in IHESCs:SRC-1 ISO were reduced by 5.0-fold by 20 nM bufalin at 48-hour treatment compared with the levels after vehicle treatment (Fig. 2C).”
Quote in the paperSubstantial claim - Findingown data
Overexpression of both PSMD2 and UBA7 did not degrade ERα or SRC-1 isoform proteins.
“overexpression of both PSMD2 and UBA7 did not result in the degradation of ERα and SRC-1 isoform proteins (Figs. 4D and 4E).”
Quote in the paperSubstantial claim - Findingown data
Bufalin treatment increased apoptosis signaling in epithelial cells of endometriotic lesions.
“Bufalin treatment elevated the apoptosis signaling in epithelial cells of endometriotic lesions.”
Quote in the paperSubstantial claim- Rests on an assumption: The surgically induced mouse model of endometriosis is representative of human endometriosis for evaluating bufalin's effects.
- Findingown data
Bufalin treatment increased expression of ER-stress markers (PERK, PDI, and BiP) in endometriotic lesions.
“bufalin treatment increased the expression levels of endoplasmic reticulum (ER)-stress markers (PKR-like ER kinase, protein disulfide isomerase and binding immunoglobulin) in endometriotic lesions.”
Quote in the paperNot a substantial claim- Rests on an assumption: The surgically induced mouse model of endometriosis is representative of human endometriosis for evaluating bufalin's effects.
- Findingown data
Bufalin treatment elevated active IL-1β by 5.1-fold (p=0.0001) in stromal cells from endometriotic lesions compared with vehicle.
“bufalin treatment, compared with the vehicle, elevated the active form of IL-1β by 5.1-fold (p=0.0001) in stromal cells but not in epithelial cells (Figs. 6A, 6B and 6C).”
Quote in the paperSubstantial claim - Findingown data
Caspase 1 levels were not elevated in epithelial cells from bufalin-treated endometriotic lesions compared with vehicle-treated lesions.
“IHC revealed that the levels of caspase 1 were elevated by 2.9-fold (p=0.0015) in stromal cells, but not in epithelial cells, from bufalin-treated endometriotic lesions compared to the vehicle-treated lesions (Figs. 6D, 6E and 6F).”
Quote in the paperSubstantial claim - Findingown data
Bufalin treatment did not elevate active caspase 3 levels in uteri of normal mice compared with vehicle.
“In addition to proliferation, the level of the active form of caspase 3 was not elevated in uteri by bufalin treatment compared to the vehicle (Fig. 8B).”
Quote in the paperSubstantial claim - Findingown data
Caspase 1 levels were elevated by 2.9-fold (p=0.0015) in stromal cells from bufalin-treated endometriotic lesions compared with vehicle-treated lesions.
“IHC revealed that the levels of caspase 1 were elevated by 2.9-fold (p=0.0015) in stromal cells, but not in epithelial cells, from bufalin-treated endometriotic lesions compared to the vehicle-treated lesions (Figs. 6D, 6E and 6F).”
Quote in the paperSubstantial claim - Findingown data
PDI levels were elevated by 4.2-fold (P=0.0015) in epithelial cells from endometriotic lesions treated with bufalin compared with vehicle.
“The PDI levels were also elevated in epithelial cells (by 4.2-fold, P=0.0015) and stromal cells (by 2.9-fold, P=0.0001) in endometriotic lesions treated with bufalin compared with the vehicle (Figs. 7D, 7E, and 7F).”
Quote in the paperSubstantial claim - Findingown data
Active caspase 3 was not detected in stromal cells of endometriotic lesions treated with either bufalin or vehicle.
“In contrast with epithelial cells, however, the active form of caspase 3 was not detected in stromal cells in endometriotic lesions treated with bufalin and vehicle (Fig. 5F).”
Quote in the paperNot a substantial claim - Findingown data
Bufalin treatment did not reduce proliferation activity in uteri of normal mice compared with vehicle.
“IHC with Ki-67 antibody revealed that compared to the vehicle, the bufalin treatment did not reduce the proliferation activity in uteri (Fig. 8A).”
Quote in the paperSubstantial claim - Findingown data
PDI levels were elevated by 2.9-fold (P=0.0001) in stromal cells from endometriotic lesions treated with bufalin compared with vehicle.
“The PDI levels were also elevated in epithelial cells (by 4.2-fold, P=0.0015) and stromal cells (by 2.9-fold, P=0.0001) in endometriotic lesions treated with bufalin compared with the vehicle (Figs. 7D, 7E, and 7F).”
Quote in the paperSubstantial claim - Findingown data
Bufalin treatment did not increase TUNEL-positive cells in stromal cells of endometriotic lesions compared with vehicle.
“In contrast with epithelial cells, however, bufalin, compared with the vehicle, did not elevate TUNEL-positive cells in stromal cells of endometriotic lesions (Fig. 5I).”
Quote in the paperNot a substantial claim - Findingown data
Bufalin treatment elevated PERK expression by 9.1-fold (p=0.0001) in epithelial cells from endometriotic lesions compared with vehicle.
“Compared to the vehicle, bufalin treatment elevated the expression levels of PERK by 9.1-fold (p=0.0001) in epithelial cells from endometriotic lesions (Figs. 7A and 7B).”
Quote in the paperSubstantial claim - Findingown data
Bufalin treatment increased the number of TUNEL-positive cells in epithelial cells of endometriotic lesions compared with vehicle.
“the TUNEL assay also revealed that compared with the vehicle, the bufalin treatment increased the number of TUNEL-positive cells in epithelial cells of the endometriotic lesions (Figs. 5G and 5H).”
Quote in the paperSubstantial claim - Findingown data
Bufalin increased PERK levels in stromal cells from endometriotic lesions by 4.1-fold (P=0.0001) compared with vehicle.
“In addition to the epithelial compartment, bufalin also increased PERK levels in stromal cells from endometriotic lesions by 4.1-fold (P=0.0001) (Fig. 7C).”
Quote in the paperSubstantial claim - Findingown data
BiP levels were elevated by 2.1-fold (P=0.015) in stromal cells from endometriotic lesions treated with bufalin compared with vehicle.
“The bufalin treatment also elevated BiP levels (by 2.1-fold, P=0.015) in stromal cells from endometriotic lesions by bufalin compared with the vehicle (Fig. 7I).”
Quote in the paperSubstantial claim - Findingown data
BiP levels were elevated by 4.6-fold (p=0.003) in epithelial cells from endometriotic lesions treated with bufalin compared with vehicle.
“Levels of BiP were elevated by 4.6-fold (p=0.003) in epithelial cells from endometriotic lesions treated with bufalin compared with the vehicle (Figs. 7G and 7H).”
Quote in the paperSubstantial claim - Findingown data
Bufalin treatment did not elevate pyroptosis signaling in uteri of normal mice compared with vehicle.
“IHC with the active form of IL-1β also revealed that the pyroptosis signaling was not elevated in uteri by bufalin treatment compared to the vehicle (Fig. 8 C).”
Quote in the paperSubstantial claim - Findingown data
Bufalin treatment did not elevate active IL-1β in epithelial cells from endometriotic lesions compared with vehicle.
“bufalin treatment, compared with the vehicle, elevated the active form of IL-1β by 5.1-fold (p=0.0001) in stromal cells but not in epithelial cells (Figs. 6A, 6B and 6C).”
Quote in the paperNot a substantial claim - Findingnone given
Bufalin hyperactivates the SRC-1 isoform function, unlike full-length SRC-1, in endometriotic lesions.
“However, bufalin hyperactivates the SRC-1 isoform function, unlike that of full-length SRC-1, in endometriotic lesions.”
Quote in the paperNot a substantial claim - Findingreasoning
Bufalin treatment degrades ERβ in endometriotic lesions.
“The second explanation is that bufalin treatment degrades ERβ in endometriotic lesions.”
Quote in the paperSubstantial claim - Findingnone given
Bufalin-induced hyperactivation of SRC-1 isoform activity suppressed the growth of endometriotic lesions compared with vehicle.
“However, the bufalin-induced hyperactivation of the SRC-1 isoform activity suppressed the growth of endometriotic lesions compared to that of the vehicle.”
Quote in the paperSubstantial claim - Findingnone given
PSMD2 did not degrade ERα protein.
“Interestingly, PSMD2 did not degrade ERα protein.”
Quote in the paperSubstantial claim - Findingreasoning
Bufalin-induced elevation of PSMD2 suppresses the growth of endometriotic lesions.
“In contrast with this finding, however, the bufalin-induced elevation of PSMD2 suppresses the growth of endometriotic lesions.”
Quote in the paperSubstantial claim - Findingown data
IHC analyses revealed that the two different cell death signaling pathways are detected in different cellular compartments of endometriotic lesions.
“However, IHC analyses revealed that the two different cell death signaling pathways are detected in different cellular compartments of endometriotic lesions.”
Quote in the paperSubstantial claim - Findingreasoning
Bufalin treatment elevated levels of PSMD2 in endometriotic lesions.
“To degrade ERβ protein, bufalin treatment elevated levels of PSMD2 in endometriotic lesions.”
Quote in the paperSubstantial claim - Findingreasoning
Bufalin treatment hyperelevated the levels of the active form of IL-β in the stromal compartments of endometriotic lesions compared with vehicle-treated endometriotic lesions.
“However, bufalin treatment hyperelevated the levels of the active form of IL-β in the stromal compartments of endometriotic lesions compared to the vehicle-treated endometriotic lesions.”
Quote in the paperSubstantial claim - Interpretationown data
Overexpression of the SRC-1 isoform in human endometrial epithelial and stromal cells increased their sensitivity to bufalin.
“Therefore, the overexpression of the SRC-1 isoform in human endometrial epithelial and stromal cells increased the sensitivity against bufalin.”
Quote in the paperSubstantial claim - Interpretationown data
Endometriotic cells were more sensitive to bufalin than normal endometrial cells.
“Therefore, endometriotic cells were more sensitive to bufalin treatment than normal endometrial cells.”
Quote in the paperSubstantial claim - Premisecitation
The SRC-1 isoform/ERβ axis is essential for the progression of endometriosis.
“The steroid receptor coactivator (SRC)-1 isoform/estrogen receptor (ER)-β axis has an essential role in endometriosis progression.”
- Also stated in: § Introduction · plain
“this SRC-1 isoform/ERβ axis has an essential role in endometriosis progression because this axis prevents TNFα-mediated apoptosis and enhances inflammasome-mediated inflammatory signaling in endometriotic lesions for their survival (Han, et al. 2012; Han, et al. 2015).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Han et al. 2012
Not checked in the free run.
- cites Han et al. 2015
Not checked in the free run.
- Also stated in: § Introduction · plain
- Interpretationown data
Bufalin disrupts the SRC-1 isoform/ERβ axis in endometriotic lesions by degrading ERβ protein through increased PSMD2.
“Collectively, these results imply that bufalin disrupts the SRC-1 isoform/ERβ axis in endometriotic lesions by degrading ERβ protein through the elevation of PSMD2.”
Quote in the paperSubstantial claim- Rests on an assumption: The surgically induced mouse model of endometriosis is representative of human endometriosis for evaluating bufalin's effects.
- Interpretationown data
Bufalin-mediated degradation of full-length SRC-1 may be associated with increased PSMD2 in endometriotic lesions.
“Therefore, bufalin-mediated degradation of the full-length SRC-1 might be associated with elevation of PSMD2 in endometriotic lesions.”
Quote in the paperSubstantial claim - Interpretationreasoning
Multiple cellular dysregulations caused by bufalin treatment in endometriotic lesions lead to suppression of endometriosis progression.
“These multiple cellular dysregulations by bufalin treatment in endometriotic lesions cause the suppression of endometriosis progression.”
Quote in the paperSubstantial claim - Interpretationown data
Bufalin treatment might be associated with elevated signaling of active IL-1β through activation of pyroptosis signaling in stromal compartments of endometriotic lesions.
“Therefore, bufalin treatment might be associated with elevated signaling of the active form of IL-1β by activating the pyroptosis signaling in stromal compartments of endometriotic lesions.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Ying and Padanilam 2016
Not checked in the free run.
- cites Miao, et al. 2011
Not checked in the free run.
- Interpretationown data
Bufalin treatment mainly stimulates ER-stress signaling in endometriotic lesions.
“Therefore, bufalin treatment mainly stimulates ER-stress signaling in endometriotic lesions.”
Quote in the paperSubstantial claim - Interpretationcitation
Overstimulating the SRC oncogenic program can be an effective strategy to kill cancer cells.
“Therefore, overstimulating the SRC oncogenic program can be an effective strategy to kill cancer cells.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Wang, et al. 2015
Not checked in the free run.
- Premisecitation
Overexpression of the SRC-1 isoform in IHEECs prevented TNFα-induced apoptosis because IHEECs express ERβ.
“Our previous study revealed that overexpression of the SRC-1 isoform in IHEECs prevented TNFα-induced apoptosis because IHEECs express ERβ (Han et al. 2012).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Han et al. 2012
Not checked in the free run.
- Premisecitation
The SRC-1 isoform has an essential role in endometriosis progression.
“Since the SRC-1 isoform has an essential role in endometriosis progression, further activation of the SRC-1 isoform in endometriotic lesions might stimulate endometriosis progression.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Han et al. 2012
Not checked in the free run.
- Interpretationown data
Bufalin treatment impaired endometriosis-stimulating ERβ signaling in endometriotic lesions by degrading ERβ protein.
“In addition to the SRC-1 isoform, bufalin treatment also impaired endometriosis-stimulating ERβ signaling in endometriotic lesions by degrading ERβ protein.”
Quote in the paperSubstantial claim - Premisecitation
ERβ is a key driver along with the SRC-1 isoform for endometriosis progression by preventing TNFβ-induced apoptosis and activating inflammasomes.
“ERβ has been known as a key driver along with the SRC-1 isoform for endometriosis progression by preventing TNFβ-induced apoptosis and activating inflammasomes (Han et al. 2015; Monsivais, et al. 2014).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Han et al. 2015
Not checked in the free run.
- cites Monsivais, et al. 2014
Not checked in the free run.
- Interpretationown data
The disruption of the SRC-1 isoform/ERβ axis by bufalin stimulates both pyroptosis and apoptosis signaling in endometriotic lesions.
“The disruption of the SRC-1 isoform/ERβ axis by bufalin stimulates both pyroptosis and apoptosis signaling in endometriotic lesions.”
Quote in the paperSubstantial claim - Interpretationreasoning
The side effects of current endometriosis treatment are partly due to the inhibition of ERα signaling in these estrogen target tissues.
“The side effects of current endometriosis treatment are partly due to the inhibition of ERα signaling in these estrogen target tissues.”
Quote in the paperSubstantial claim - Interpretationown data
Bufalin induced pyroptosis in the stromal compartments of endometriotic lesions by elevating the active form of IL-1β and caspase 1 in stromal cells.
“Here, we revealed that bufalin induced pyroptosis in the stromal compartments of endometriotic lesions by elevating the active form of IL-1β and caspase 1 in stromal cells.”
Quote in the paperSubstantial claim - Premisecitation
Hyperactivating IL-1β signaling induced ER stresses, resulting in cell death in human pancreatic cells.
“Hyperactivating IL-1β signaling induced ER stresses, resulting in cell death in human pancreatic cells (Verma and Datta 2010).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Verma and Datta 2010
Not checked in the free run.
- Interpretationcitation
Bufalin itself may not be an ideal drug for endometriosis.
“It appears that bufalin itself may not be an ideal drug for endometriosis.”
Quote in the paperSubstantial claim
- May combine two claims. 41
- Classified as probably not a substantial claim. 12
May combine two claims.
Findingown dataIn stromal cells of endometriotic lesions, bufalin treatment increased pyroptosis markers (caspase 1 and active IL-1β) and reduced proliferation.
“In stromal cells of endometriotic lesions, bufalin treatment increased the levels of pyroptosis markers (caspase 1 and the active form of interleukin 1β) and reduced proliferation.”
Quote in the paperSubstantial claim- Rests on an assumption: The surgically induced mouse model of endometriosis is representative of human endometriosis for evaluating bufalin's effects.
May combine two claims.
Findingown dataFull-length SRC-1 was degraded by PSMD2 but not by UBA7.
“the full-length SRC-1 was degraded by PSMD2 but not by UBA7 (Fig. 4F).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataBufalin treatment (1 mg/kg for 21 days) did not reduce reproductive activity or disrupt fertility in female mice compared with vehicle.
“The female mouse fertility assay revealed that compared with vehicle treatment, bufalin treatment did not reduce the reproductive activity in female mice (Fig. 8D).”
- Also stated in: § Bufalin treatment did not impair normal uterine function of mice without endometriosis · plain
“In our hands, therefore, the 21-day bufalin treatment (1 mg/kg) did not disrupt the fertility of female mice.”
- Also stated in: § Conclusion · plain
“Our study also revealed that 21-day bufalin treatment (1 mg/kg) did not impair normal uterine function and fertility.”
Quote in the paperSubstantial claim- Also stated in: § Bufalin treatment did not impair normal uterine function of mice without endometriosis · plain
May combine two claims.
FindingreasoningBufalin treatment increased the SRC-1 isoform level and its transcriptional activity in endometriotic lesions.
“Similar to SRC-1 isoform overexpression, bufalin treatment increased the SRC-1 isoform level and its transcriptional activity in endometriotic lesions.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataActivation of pyroptosis and apoptosis are detected in stromal and epithelial cells of endometriotic lesions, respectively.
“For example, activation of pyroptosis and apoptosis are detected in stromal and epithelial cells of endometriotic lesions, respectively.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationThe SRC-1 isoform and ERβ are present at higher levels in endometriotic tissue than in normal endometrium.
“our prior study revealed that a steroid receptor coactivator (SRC)-1 isoform that is proteolytically cleaved from the full-length SRC-1 by matrix metalloproteinase-9 and estrogen receptor (ER) β are specifically elevated in endometriotic tissues compared to the normal endometrium”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Han et al. 2012
Not checked in the free run.
- cites Han et al. 2015
Not checked in the free run.
May combine two claims.
PremisecitationBufalin inhibits the intrinsic transcriptional activity of SRC-1 and SRC-3 and degrades their proteins in various cancer cells, suppressing their growth.
“Bufalin, one of the SRC-SMIs, inhibited the intrinsic transcriptional activity of SRC-1 and -3 and degraded their proteins in various cancer cells to suppress their growth (Wang et al. 2014).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Wang et al. 2014
Not checked in the free run.
May combine two claims.
PremisecitationThe SRC-1 isoform/ERβ axis blocks TNFα-induced apoptosis and promotes inflammasome-mediated inflammatory signaling in endometriotic lesions, supporting their survival.
“this SRC-1 isoform/ERβ axis has an essential role in endometriosis progression because this axis prevents TNFα-mediated apoptosis and enhances inflammasome-mediated inflammatory signaling in endometriotic lesions for their survival (Han, et al. 2012; Han, et al. 2015).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Han et al. 2012
Not checked in the free run.
- cites Han et al. 2015
Not checked in the free run.
May combine two claims.
PremisecitationBufalin and gossypol are small-molecule inhibitors that reduce SRC activity and protein stability and inhibit growth of various cancer cells.
“Our previous studies defined small molecular inhibitors (SMIs), such as bufalin and gossypol, that diminished the activities and protein stabilities of SRCs and suppressed the growth of various cancer cells (Wang, et al. 2011; Wang, et al. 2014).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Wang et al. 2011
Not checked in the free run.
- cites Wang et al. 2014
Not checked in the free run.
May combine two claims.
Interpretationown dataBufalin hyperactivated SRC-1 isoform function in endometriotic lesions by stabilizing the SRC-1 isoform protein and stimulating its transcriptional activity.
“Collectively, bufalin hyperactivated the SRC-1 isoform function in endometriotic lesions by stabilizing the SRC-1 isoform protein, stimulating its transcriptional activity.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
Study design and conductnone givenMice with endometriosis were randomly divided into two groups before receiving vehicle or 1 mg/kg bufalin daily for 21 days.
“After endometriotic lesions were established (one week after endometriosis induction), the mice were randomly divided into two groups and then subcutaneously administered vehicle (as the control) or 1 mg/kg of bufalin daily for 21 days.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationIHESCs are karyotypically, morphologically, and phenotypically similar to primary parent cells, and IHEECs retain normal functions and characteristics of primary cells.
“because IHESCs are karyotypically, morphologically, and phenotypically similar to the primary parent cells (Krikun et al. 2004) and because IHEECs also retain the normal functions and characteristics of the primary cells (Kyo, et al. 2003).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Krikun et al. 2004
Not checked in the free run.
- cites Kyo et al. 2003
Not checked in the free run.
May combine two claims.
Interpretationown dataBufalin disrupted the SRC-1 isoform/ERβ axis in endometriotic lesions by raising SRC-1 isoform protein levels and lowering ERβ protein levels, leading to suppressed endometriosis progression.
“Therefore, bufalin treatment disrupted the SRC-1 isoform/ERβ axis by increasing SRC-1 isoform protein levels, decreasing ERβ protein levels in endometriotic lesions, and then suppressing endometriosis progression.”
Quote in the paperSubstantial claim- Rests on an assumption: The surgically induced mouse model of endometriosis is representative of human endometriosis for evaluating bufalin's effects.
May combine two claims.
Interpretationown dataBufalin treatment lowered ERβ protein levels but did not inhibit ERβ transcriptional activity in endometriotic lesions.
“Therefore, bufalin treatment decreased the protein levels of ERβ but did not inhibit its transcriptional activity in endometriotic lesions.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataBufalin treatment significantly reduced proliferation of endometrial stromal cells but not epithelial cells from endometriotic lesions.
“Therefore, the bufalin treatment significantly reduced the proliferation of endometrial stromal cells but not that of epithelial cells from endometriotic lesions.”
Quote in the paperSubstantial claim- Rests on an assumption: The surgically induced mouse model of endometriosis is representative of human endometriosis for evaluating bufalin's effects.
May combine two claims.
InterpretationreasoningBufalin-induced disruption of the SRC-1 isoform/ERβ axis may induce apoptosis, pyroptosis, and ER-stress signaling in endometriotic lesions, causing suppression of endometriosis.
“Collectively, the bufalin-induced disruption of the SRC-1 isoform/ERβ axis might induce apoptosis, pyroptosis and ER-stress signaling in endometriotic lesions, causing the suppression of endometriosis.”
Quote in the paperSubstantial claim- Rests on an assumption: The surgically induced mouse model of endometriosis is representative of human endometriosis for evaluating bufalin's effects.
May combine two claims.
Interpretationnone givenBufalin degrades ERβ protein by elevating PSMD2 and hyperactivates SRC-1 isoform function in endometriotic lesions.
“Bufalin degrades ERβ protein by elevating PSMD2 and hyperactivates SRC-1 isoform function in endometriotic lesions.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningDisruption of the bufalin-induced SRC-1 isoform/ERβ axis is associated with activation of apoptosis signaling in epithelial cells and reduced proliferation of stromal cells.
“This disruption of the bufalin-induced SRC-1 isoform/ERβ axis is associated with activation of apoptosis signaling in epithelial cells and reduces the proliferation of stromal cells.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataBufalin treatment is associated with increased apoptosis signaling in epithelial cells and decreased proliferation of stromal cells from endometriotic lesions.
“Collectively, bufalin treatment is associated with elevation of apoptosis signaling in epithelial cells and reduction of proliferation of stromal cells from endometriotic lesions.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationBufalin is a traditional oriental medicine used for cancer treatment because it induces apoptosis in cancer cells.
“Bufalin has been known as a traditional oriental medicine and used for cancer treatment because it induces apoptosis in cancer cells (Takai, et al. 2012).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Takai, et al. 2012
Not checked in the free run.
May combine two claims.
InterpretationreasoningBufalin treatment stimulates pyroptosis in stromal cells and then elevates ER stress signaling in endometriotic lesions.
“In addition, bufalin treatment stimulates the pyroptosis in stromal cells and then elevates ER stress signaling in endometriotic lesions.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningBufalin is an activator of the SRC-1 isoform, whereas it acts as an inhibitor against full-length SRC-1.
“Therefore, bufalin is an activator of the SRC-1 isoform, whereas it acts as an inhibitor against full-length SRC-1.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningOver-stimulating the endometriosis-promoting SRC-1 isoform using bufalin could kill endometriotic lesions by promoting ER stress induced by pyroptosis, similar to MCB613.
“In the same context, therefore, over-stimulating the endometriosis-promoting SRC-1 isoform using bufalin could kill endometriotic lesions by promoting ER stress induced by pyroptosis, similar to MCB613.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationTo prevent apoptosis in endometriotic lesions, both the SRC-1 isoform and ERβ axis are required because the SRC-1 isoform/ERβ complex interacts with the apoptosis machinery in endometriotic lesions.
“To prevent apoptosis in endometriotic lesions, both the SRC-1 isoform and ERβ axis are required because the SRC-1 isoform/ERβ complex interacts with the apoptosis machinery in endometriotic lesions (Han et al. 2015).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Han et al. 2015
Not checked in the free run.
May combine two claims.
InterpretationreasoningEven though bufalin elevated SRC-1 isoform function in endometriotic lesions, bufalin did not prevent apoptosis in endometriotic lesions without ERβ and then reactivated apoptosis signaling.
“Even though bufalin elevated SRC-1 isoform function in endometriotic lesions, however, bufalin did not prevent apoptosis in endometriotic lesions without ERβ and then reactivated apoptosis signaling.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningBufalin treatment suppressed the growth of endometriotic lesions because ERβ levels were reduced in endometriotic lesions.
“However, bufalin treatment suppressed the growth of endometriotic lesions because ERβ levels were reduced in endometriotic lesions.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationBufalin induces apoptosis and G0/G1 cell cycle arrest in endometriotic stromal cells in vitro.
“In addition to cancer cells, bufalin also induces apoptosis and G0/G1 cell cycle arrest in endometriotic stromal cells in vitro (Nasu, et al. 2005).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Nasu, et al. 2005
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationBufalin inhibits SRC-1 and SRC-3 functions by degrading their protein levels and inhibiting their intrinsic transcriptional activities in various cancer cells.
“Bufalin inhibits SRC-1 and SRC-3 functions by degrading their protein levels and inhibiting their intrinsic transcriptional activities in various cancer cells (Wang et al. 2014).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Wang et al. 2014
Not checked in the free run.
Classified as probably not a substantial claim.
InterpretationreasoningFurther activation of the SRC-1 isoform in endometriotic lesions might stimulate endometriosis progression.
“Since the SRC-1 isoform has an essential role in endometriosis progression, further activation of the SRC-1 isoform in endometriotic lesions might stimulate endometriosis progression.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationcitationThe molecular effects of bufalin on the SRC-1 isoform are quite similar to those of MCB613.
“The first explanation is that the molecular effects of bufalin on the SRC-1 isoform are quite similar to those of another newly discovered small molecule named MCB613.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Wang, et al. 2015
Not checked in the free run.
May combine two claims.
InterpretationreasoningERβ should be the best target to suppress endometriosis progression because deactivation of ERβ could reactivate TNFα-induced apoptosis signaling only in endometriotic lesions to suppress their growth.
“Therefore, ERβ should be the best target to suppress endometriosis progression because the deactivation of ERβ could reactivate TNFα-induced apoptosis signaling only in endometriotic lesions to suppress their growth.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningIn endometriotic tissues, PSMD2 specifically recognizes ERβ, an essential endometriosis driver, and then degrades it to suppress the ERβ-regulated gene signature that is required for endometriosis progression.
“In endometriotic tissues, therefore, PSMD2 specifically recognizes ERβ, an essential endometriosis driver, and then degrades it to suppress the ERβ-regulated gene signature that is required for endometriosis progression.”
Quote in the paperSubstantial claim- Rests on an assumption: PSMD2 is a component of the 19S regulatory component and is responsible for substrate recognition and binding.
May combine two claims.
PremisecitationERα has critical roles in estrogen target tissues in addition to endometriosis progression, and estrogen deficiency affects different tissues, resulting in an increase in various diseases such as osteoporosis or cardiovascular diseases.
“ERα has critical roles in estrogen target tissues in addition to endometriosis progression, and estrogen deficiency affects different tissues, resulting in an increase in various diseases such as osteoporosis or cardiovascular diseases (Valera, et al. 2015).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Valera, et al. 2015
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe proteasome also has an essential role in cell death signaling.
“In addition to survival functions, the proteasome also has an essential role in cell death signaling (Vacca, et al. 2007).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Vacca, et al. 2007
Not checked in the free run.
May combine two claims.
InterpretationreasoningThe bufalin/PSMD2/ERβ pathway should improve the specificity of endometriosis treatment and reduce side effects of the inhibition of ERα signaling by the current estrogen depletion therapy.
“Therefore, the bufalin/PSMD2/ERβ pathway should improve the specificity of endometriosis treatment and reduce side effects of the inhibition of ERα signaling by the current estrogen depletion therapy.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningBufalin significantly reduced ERβ levels in endometriotic lesions and then reactivated apoptosis signaling in epithelial cells from endometriotic lesions to suppress endometriosis progression.
“Therefore, bufalin significantly reduced ERβ levels in endometriotic lesions and then reactivated apoptosis signaling in epithelial cells from endometriotic lesions to suppress the endometriosis progression.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationProteasome components have a crucial role in endometriosis progression because the proteasome inhibitor bortezomib suppresses endometriosis progression in a rat endometriosis model.
“Consistent with the cancer progression, proteasome components also have a crucial role in endometriosis progression because the proteasome inhibitor bortezomib suppresses endometriosis progression in a rat endometriosis model (Celik, et al. 2008).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Celik, et al. 2008
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationElevation of PSMD2 levels drives the progression of various human diseases.
“Interestingly, the elevation of PSMD2 levels drives the progression of various human diseases.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Matsuyama, et al. 2011
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationIn lung cancer, elevated levels of PSMD2 and its gene signature are associated with acquisition of the metastatic phenotype and a poor prognosis because knockdown of PSMD2 decreases proteasome activity and induces growth inhibition and apoptosis in lung cancer cell lines.
“In lung cancer, for example, elevated levels of PSMD2 and its gene signature are associated with acquisition of the metastatic phenotype and a poor prognosis because knockdown of PSMD2 decreases proteasome activity and induces growth inhibition and apoptosis in lung cancer cell lines (Matsuyama, et al. 2011).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Matsuyama, et al. 2011
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationPyroptosis, or caspase 1-dependent cell death, is known as inflammatory cell death signaling and is initiated by various pathological stimuli, such as stroke, heart attack or cancer.
“Pyroptosis, or caspase 1-dependent cell death, is known as inflammatory cell death signaling and is initiated by various pathological stimuli, such as stroke, heart attack or cancer (Bergsbaken, et al. 2009).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Bergsbaken, et al. 2009
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationChronic treatment with a low dose of bufadienolides has been proven to be effective in certain instances, causing little to no side effects.
“Chronic treatment with a low dose of bufadienolides has been proven to be effective in certain instances, causing little to no side effects (Jing, et al. 1994; Panesar 1992).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Jing, et al. 1994
Not checked in the free run.
- cites Panesar 1992
Not checked in the free run.
May combine two claims.
InterpretationreasoningBufalin treatment elevates hyper-releasing active forms of IL-1β from pyroptotic stromal cells and enhances ER stress in endometriotic lesions to effectively suppress the growth of endometriotic lesions along with activation of apoptosis in epithelial cells of endometriotic lesions.
“Therefore, bufalin treatment elevates hyper-releasing active forms of IL-1β from pyroptotic stromal cells and enhances ER stress in endometriotic lesions to effectively suppress the growth of endometriotic lesions along with activation of apoptosis in epithelial cells of endometriotic lesions.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationIL-1β signaling has been known as a double-edged sword because the elevation of the active form of IL-1β results in proliferative activity in certain cases but also induces cell death signaling in other cases.
“IL-1β signaling has been known as a double-edged sword because the elevation of the active form of IL-1β results in proliferative activity in certain cases but also induces cell death signaling in other cases (Kolb, et al. 2014).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Kolb, et al. 2014
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationDespite this known cytotoxic property, bufadienolides have been used to treat cardiovascular and kidney diseases.
“Despite this known cytotoxic property of bufadienolides, however, they have been used to treat cardiovascular and kidney diseases (Puschett, et al. 2010).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Puschett, et al. 2010
Not checked in the free run.
May combine two claims.
PremisecitationBufalin belongs to the bufadienolide group, and bufadienolides are known for having deleterious cardiovascular side effects due to their inhibition of the transport enzyme Na+/K+-adenosine triphosphatase.
“Bufalin belongs to the bufadienolide group, and bufadienolides are known for having deleterious cardiovascular side effects due to their inhibition of the transport enzyme Na+/K+-adenosine triphosphatase (Xu, et al. 2016).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Xu, et al. 2016
Not checked in the free run.
May combine two claims.
InterpretationreasoningBufalin has potential cardiac ion channel toxicity so it is not an ideal candidate drug with which to go forward.
“We know, however, that bufalin has potential cardiac ion channel toxicity so it is not an ideal candidate drug with which to go forward.”
Quote in the paperSubstantial claim- Rests on an assumption: Bufalin has potential cardiac ion channel toxicity.
The paper relies on this without support.
The surgically induced mouse model of endometriosis is representative of human endometriosis for evaluating bufalin's effects.
“Endometriosis in mice was surgically induced under aseptic conditions under anesthesia using a modified method as described previously (Cummings and Metcalf 1995).”
The paper relies on this without support.
Findings from human endometrial cell lines and mouse models can be extrapolated to human patients for endometriosis treatment.
“Therefore, future generations of SRC-modulators could be employed as an alternative medical approach for endometriosis treatment.”
The paper relies on this without support.
More detailed studies have not been conducted to evaluate whether bufalin can be employed as an alternative medicine for endometriosis treatment.
“However, more detailed studies have not been conducted to evaluate whether bufalin can be employed as an alternative medicine for endometriosis treatment.”
The paper relies on this without support.
PSMD2 is a component of the 19S regulatory component and is responsible for substrate recognition and binding.
“PSMD2 is a component of the 19S regulatory component and is responsible for substrate recognition and binding.”
The paper relies on this without support.
The role of pyroptosis in endometriosis progression has not been reported.
“However, the role of pyroptosis in endometriosis progression has not been reported.”
The paper relies on this without support.
Bufalin has potential cardiac ion channel toxicity.
“We know, however, that bufalin has potential cardiac ion channel toxicity so it is not an ideal candidate drug with which to go forward.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Lentiviral plasmid has two different names
MinorThe construct is described as cloned into pCDH-pCMV, but the subsequent transfection names pCDH-pCNV-SRC-1 isoform. No intervening change of vector is described.
“The open reading frame of the SRC-1 isoform gene was cloned into a pCDH-pCMV vector using BamH1 and XhoI restriction enzymes.”
“Next, 293T cells on a 100-cm tissue culture dish were transfected with the pCDH-pCNV-SRC-1 isoform and Lenti-X packaging single shot”
Epithelial and stromal cell labels are reversed
MinorThe methods identify IHESCs as stromal cells and IHEECs as epithelial cells, but the results assign those identities in the opposite order.
“we employed IHESCs and IHEECs as human endometrial epithelial and stromal cell lines, respectively”
“immortalized human endometrial stromal cells (IHESCs) (Krikun, et al. 2004), EMosis-CC/TERT1 (immortalized human endometriotic epithelial cells; IHEECs)”
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Flagged first, then by citations
Research works printed but not linked: 46
- 2017, Endometriosis and the risk of skin cancer: a prospective cohort study, Cancer Causes and Control, 28, 1011, 10.1007/s10552-017-0939-2 · DOI
- 2016, Laparoscopically confirmed endometriosis and breast cancer in the Nurses’ Health Study II, Obstetrics and Gynecology, 128, 1025, 10.1097/AOG.0000000000001684 · DOI
- 2010, IL-1beta induces ER stress in a JNK dependent manner that determines cell death in human pancreatic epithelial MIA PaCa-2 cells, Apoptosis, 15, 864, 10.1007/s10495-010-0498-4 · DOI
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Cited by
Sorted by citations
Endometriosis and nuclear receptors
Yilmaz, B. D., & Bulun, S. E. (2019) · Human Reproduction Update · doi:10.1093/humupd/dmz005 · Cited by 243 · see citing works
Doroftei, B., Ilie, O.-D., Balmus, I.-M., Ciobica, A., Maftei, R., Scripcariu, I., Simionescu, G., Grab, D., Stoian, I., & Ilea, C. (2021) · Diagnostics · doi:10.3390/diagnostics11081434 · Cited by 19 · see citing works
- Authors
- Cho, Y. J., Lee, J. E., Park, M. J., O’Malley, B. W., & Han, S. J.
- Affiliations
- Baylor College of Medicine (US)
- Corresponding author
- Han, Sang Jun
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2018-06
- Volume
- 237
- Issue
- 3
- Pages
- 255-269
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- PMC
- PMC5943165
- OpenAlex
- W2797374082
- Cited by
- 37
- References
- 46
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 6 · 2023: 6 · 2022: 3 · 2021: 10 · 2020: 1 · 2019: 3 · 2018: 1
- FWCI
- 4.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Hogg Foundation for Mental Health
- National Institute of Diabetes and Digestive and Kidney Diseases (U24DK097748, DK097748)
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD082786, R01HD008188)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- bufalin, endometriosis, pyroptosis, apoptosis, estrogen receptor beta, steroid receptor coactivators, endometrial stromal cells, endometrial epithelial cells, caspase-1, IL-1β, endoplasmic reticulum stress, protein disulfide isomerase, BAIAP2, proteasomal degradation, endometriosis treatment
- MeSH terms
- Pyroptosis, Animals, Bufanolides, Cells, Cultured, Endometriosis, Endometrium, Female, Fertility, HeLa Cells, Humans, Litter Size, Mice, Inbred C57BL, Pregnancy, Uterine Diseases, Signal Transduction, Down-Regulation, Stromal Cells, Apoptosis, Disease Progression, Mice
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