1.Acute Inflammatory Pain Induces Sex-different Brain Alpha Activity in Anesthetized Rats Through Optically Pumped Magnetometer Magnetoencephalography
Meng-Meng MIAO ; Yu-Xuan REN ; Wen-Wei WU ; Yu ZHANG ; Chen PAN ; Xiang-Hong LIN ; Hui-Dan LIN ; Xiao-Wei CHEN
Progress in Biochemistry and Biophysics 2025;52(1):244-257
ObjectiveMagnetoencephalography (MEG), a non-invasive neuroimaging technique, meticulously captures the magnetic fields emanating from brain electrical activity. Compared with MEG based on superconducting quantum interference devices (SQUID), MEG based on optically pump magnetometer (OPM) has the advantages of higher sensitivity, better spatial resolution and lower cost. However, most of the current studies are clinical studies, and there is a lack of animal studies on MEG based on OPM technology. Pain, a multifaceted sensory and emotional phenomenon, induces intricate alterations in brain activity, exhibiting notable sex differences. Despite clinical revelations of pain-related neuronal activity through MEG, specific properties remain elusive, and comprehensive laboratory studies on pain-associated brain activity alterations are lacking. The aim of this study was to investigate the effects of inflammatory pain (induced by Complete Freund’s Adjuvant (CFA)) on brain activity in a rat model using the MEG technique, to analysis changes in brain activity during pain perception, and to explore sex differences in pain-related MEG signaling. MethodsThis study utilized adult male and female Sprague-Dawley rats. Inflammatory pain was induced via intraplantar injection of CFA (100 μl, 50% in saline) in the left hind paw, with control groups receiving saline. Pain behavior was assessed using von Frey filaments at baseline and 1 h post-injection. For MEG recording, anesthetized rats had an OPM positioned on their head within a magnetic shield, undergoing two 15-minute sessions: a 5-minute baseline followed by a 10-minute mechanical stimulation phase. Data analysis included artifact removal and time-frequency analysis of spontaneous brain activity using accumulated spectrograms, generating spectrograms focused on the 4-30 Hz frequency range. ResultsMEG recordings in anesthetized rats during resting states and hind paw mechanical stimulation were compared, before and after saline/CFA injections. Mechanical stimulation elevated alpha activity in both male and female rats pre- and post-saline/CFA injections. Saline/CFA injections augmented average power in both sexes compared to pre-injection states. Remarkably, female rats exhibited higher average spectral power 1 h after CFA injection than after saline injection during resting states. Furthermore, despite comparable pain thresholds measured by classical pain behavioral tests post-CFA treatment, female rats displayed higher average power than males in the resting state after CFA injection. ConclusionThese results imply an enhanced perception of inflammatory pain in female rats compared to their male counterparts. Our study exhibits sex differences in alpha activities following CFA injection, highlighting heightened brain alpha activity in female rats during acute inflammatory pain in the resting state. Our study provides a method for OPM-based MEG recordings to be used to study brain activity in anaesthetized animals. In addition, the findings of this study contribute to a deeper understanding of pain-related neural activity and pain sex differences.
2.Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway
Zhao LI ; Ya-Hong WU ; Ye-Qing GUO ; Xiao-Jia MIN ; Ying LIN
The Korean Journal of Physiology and Pharmacology 2025;29(2):191-204
To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.
3.Impact of iron-deficiency anemia on short-term outcomes after resection of colorectal cancer liver metastasis: a US National (Nationwide) Inpatient Sample (NIS) analysis
Ko-Chao LEE ; Yu-Li SU ; Kuen-Lin WU ; Kung-Chuan CHENG ; Ling-Chiao SONG ; Chien-En TANG ; Hong-Hwa CHEN ; Kuan-Chih CHUNG
Annals of Coloproctology 2025;41(2):119-126
Purpose:
Colorectal cancer (CRC) often spreads to the liver, necessitating surgical treatment for CRC liver metastasis (CRLM). Iron-deficiency anemia is common in CRC patients and is associated with fatigue and weakness. This study investigated the effects of iron-deficiency anemia on the outcomes of surgical resection of CRLM.
Methods:
This population-based, retrospective study evaluated data from adults ≥20 years old with CRLM who underwent hepatic resection. All patient data were extracted from the 2005–2018 US National (Nationwide) Inpatient Sample (NIS) database. The outcome measures were in-hospital outcomes including 30-day mortality, unfavorable discharge, and prolonged length of hospital stay (LOS), and short-term complications such as bleeding and infection. Associations between iron-deficiency anemia and outcomes were determined using logistic regression analysis.
Results:
Data from 7,749 patients (representing 37,923 persons in the United States after weighting) were analyzed. Multivariable analysis revealed that iron-deficiency anemia was significantly associated with an increased risk of prolonged LOS (adjusted odds ratio [aOR], 2.76; 95% confidence interval [CI], 2.30–3.30), unfavorable discharge (aOR, 2.42; 95% CI, 1.83–3.19), bleeding (aOR, 5.05; 95% CI, 2.92–8.74), sepsis (aOR, 1.60; 95% CI, 1.04–2.46), pneumonia (aOR, 2.54; 95% CI, 1.72–3.74), and acute kidney injury (aOR, 1.71; 95% CI, 1.24–2.35). Subgroup analyses revealed consistent associations between iron-deficiency anemia and prolonged LOS across age, sex, and obesity status categories.
Conclusion
In patients undergoing hepatic resection for CRLM, iron-deficiency anemia is an independent risk factor for prolonged LOS, unfavorable discharge, and several critical postoperative complications. These findings underscore the need for proactive anemia management to optimize surgical outcomes.
4.Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway
Zhao LI ; Ya-Hong WU ; Ye-Qing GUO ; Xiao-Jia MIN ; Ying LIN
The Korean Journal of Physiology and Pharmacology 2025;29(2):191-204
To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.
5.Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway
Zhao LI ; Ya-Hong WU ; Ye-Qing GUO ; Xiao-Jia MIN ; Ying LIN
The Korean Journal of Physiology and Pharmacology 2025;29(2):191-204
To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.
6.Impact of iron-deficiency anemia on short-term outcomes after resection of colorectal cancer liver metastasis: a US National (Nationwide) Inpatient Sample (NIS) analysis
Ko-Chao LEE ; Yu-Li SU ; Kuen-Lin WU ; Kung-Chuan CHENG ; Ling-Chiao SONG ; Chien-En TANG ; Hong-Hwa CHEN ; Kuan-Chih CHUNG
Annals of Coloproctology 2025;41(2):119-126
Purpose:
Colorectal cancer (CRC) often spreads to the liver, necessitating surgical treatment for CRC liver metastasis (CRLM). Iron-deficiency anemia is common in CRC patients and is associated with fatigue and weakness. This study investigated the effects of iron-deficiency anemia on the outcomes of surgical resection of CRLM.
Methods:
This population-based, retrospective study evaluated data from adults ≥20 years old with CRLM who underwent hepatic resection. All patient data were extracted from the 2005–2018 US National (Nationwide) Inpatient Sample (NIS) database. The outcome measures were in-hospital outcomes including 30-day mortality, unfavorable discharge, and prolonged length of hospital stay (LOS), and short-term complications such as bleeding and infection. Associations between iron-deficiency anemia and outcomes were determined using logistic regression analysis.
Results:
Data from 7,749 patients (representing 37,923 persons in the United States after weighting) were analyzed. Multivariable analysis revealed that iron-deficiency anemia was significantly associated with an increased risk of prolonged LOS (adjusted odds ratio [aOR], 2.76; 95% confidence interval [CI], 2.30–3.30), unfavorable discharge (aOR, 2.42; 95% CI, 1.83–3.19), bleeding (aOR, 5.05; 95% CI, 2.92–8.74), sepsis (aOR, 1.60; 95% CI, 1.04–2.46), pneumonia (aOR, 2.54; 95% CI, 1.72–3.74), and acute kidney injury (aOR, 1.71; 95% CI, 1.24–2.35). Subgroup analyses revealed consistent associations between iron-deficiency anemia and prolonged LOS across age, sex, and obesity status categories.
Conclusion
In patients undergoing hepatic resection for CRLM, iron-deficiency anemia is an independent risk factor for prolonged LOS, unfavorable discharge, and several critical postoperative complications. These findings underscore the need for proactive anemia management to optimize surgical outcomes.
7.Impact of iron-deficiency anemia on short-term outcomes after resection of colorectal cancer liver metastasis: a US National (Nationwide) Inpatient Sample (NIS) analysis
Ko-Chao LEE ; Yu-Li SU ; Kuen-Lin WU ; Kung-Chuan CHENG ; Ling-Chiao SONG ; Chien-En TANG ; Hong-Hwa CHEN ; Kuan-Chih CHUNG
Annals of Coloproctology 2025;41(2):119-126
Purpose:
Colorectal cancer (CRC) often spreads to the liver, necessitating surgical treatment for CRC liver metastasis (CRLM). Iron-deficiency anemia is common in CRC patients and is associated with fatigue and weakness. This study investigated the effects of iron-deficiency anemia on the outcomes of surgical resection of CRLM.
Methods:
This population-based, retrospective study evaluated data from adults ≥20 years old with CRLM who underwent hepatic resection. All patient data were extracted from the 2005–2018 US National (Nationwide) Inpatient Sample (NIS) database. The outcome measures were in-hospital outcomes including 30-day mortality, unfavorable discharge, and prolonged length of hospital stay (LOS), and short-term complications such as bleeding and infection. Associations between iron-deficiency anemia and outcomes were determined using logistic regression analysis.
Results:
Data from 7,749 patients (representing 37,923 persons in the United States after weighting) were analyzed. Multivariable analysis revealed that iron-deficiency anemia was significantly associated with an increased risk of prolonged LOS (adjusted odds ratio [aOR], 2.76; 95% confidence interval [CI], 2.30–3.30), unfavorable discharge (aOR, 2.42; 95% CI, 1.83–3.19), bleeding (aOR, 5.05; 95% CI, 2.92–8.74), sepsis (aOR, 1.60; 95% CI, 1.04–2.46), pneumonia (aOR, 2.54; 95% CI, 1.72–3.74), and acute kidney injury (aOR, 1.71; 95% CI, 1.24–2.35). Subgroup analyses revealed consistent associations between iron-deficiency anemia and prolonged LOS across age, sex, and obesity status categories.
Conclusion
In patients undergoing hepatic resection for CRLM, iron-deficiency anemia is an independent risk factor for prolonged LOS, unfavorable discharge, and several critical postoperative complications. These findings underscore the need for proactive anemia management to optimize surgical outcomes.
8.Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway
Zhao LI ; Ya-Hong WU ; Ye-Qing GUO ; Xiao-Jia MIN ; Ying LIN
The Korean Journal of Physiology and Pharmacology 2025;29(2):191-204
To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.
9.Impact of iron-deficiency anemia on short-term outcomes after resection of colorectal cancer liver metastasis: a US National (Nationwide) Inpatient Sample (NIS) analysis
Ko-Chao LEE ; Yu-Li SU ; Kuen-Lin WU ; Kung-Chuan CHENG ; Ling-Chiao SONG ; Chien-En TANG ; Hong-Hwa CHEN ; Kuan-Chih CHUNG
Annals of Coloproctology 2025;41(2):119-126
Purpose:
Colorectal cancer (CRC) often spreads to the liver, necessitating surgical treatment for CRC liver metastasis (CRLM). Iron-deficiency anemia is common in CRC patients and is associated with fatigue and weakness. This study investigated the effects of iron-deficiency anemia on the outcomes of surgical resection of CRLM.
Methods:
This population-based, retrospective study evaluated data from adults ≥20 years old with CRLM who underwent hepatic resection. All patient data were extracted from the 2005–2018 US National (Nationwide) Inpatient Sample (NIS) database. The outcome measures were in-hospital outcomes including 30-day mortality, unfavorable discharge, and prolonged length of hospital stay (LOS), and short-term complications such as bleeding and infection. Associations between iron-deficiency anemia and outcomes were determined using logistic regression analysis.
Results:
Data from 7,749 patients (representing 37,923 persons in the United States after weighting) were analyzed. Multivariable analysis revealed that iron-deficiency anemia was significantly associated with an increased risk of prolonged LOS (adjusted odds ratio [aOR], 2.76; 95% confidence interval [CI], 2.30–3.30), unfavorable discharge (aOR, 2.42; 95% CI, 1.83–3.19), bleeding (aOR, 5.05; 95% CI, 2.92–8.74), sepsis (aOR, 1.60; 95% CI, 1.04–2.46), pneumonia (aOR, 2.54; 95% CI, 1.72–3.74), and acute kidney injury (aOR, 1.71; 95% CI, 1.24–2.35). Subgroup analyses revealed consistent associations between iron-deficiency anemia and prolonged LOS across age, sex, and obesity status categories.
Conclusion
In patients undergoing hepatic resection for CRLM, iron-deficiency anemia is an independent risk factor for prolonged LOS, unfavorable discharge, and several critical postoperative complications. These findings underscore the need for proactive anemia management to optimize surgical outcomes.
10.Impact of iron-deficiency anemia on short-term outcomes after resection of colorectal cancer liver metastasis: a US National (Nationwide) Inpatient Sample (NIS) analysis
Ko-Chao LEE ; Yu-Li SU ; Kuen-Lin WU ; Kung-Chuan CHENG ; Ling-Chiao SONG ; Chien-En TANG ; Hong-Hwa CHEN ; Kuan-Chih CHUNG
Annals of Coloproctology 2025;41(2):119-126
Purpose:
Colorectal cancer (CRC) often spreads to the liver, necessitating surgical treatment for CRC liver metastasis (CRLM). Iron-deficiency anemia is common in CRC patients and is associated with fatigue and weakness. This study investigated the effects of iron-deficiency anemia on the outcomes of surgical resection of CRLM.
Methods:
This population-based, retrospective study evaluated data from adults ≥20 years old with CRLM who underwent hepatic resection. All patient data were extracted from the 2005–2018 US National (Nationwide) Inpatient Sample (NIS) database. The outcome measures were in-hospital outcomes including 30-day mortality, unfavorable discharge, and prolonged length of hospital stay (LOS), and short-term complications such as bleeding and infection. Associations between iron-deficiency anemia and outcomes were determined using logistic regression analysis.
Results:
Data from 7,749 patients (representing 37,923 persons in the United States after weighting) were analyzed. Multivariable analysis revealed that iron-deficiency anemia was significantly associated with an increased risk of prolonged LOS (adjusted odds ratio [aOR], 2.76; 95% confidence interval [CI], 2.30–3.30), unfavorable discharge (aOR, 2.42; 95% CI, 1.83–3.19), bleeding (aOR, 5.05; 95% CI, 2.92–8.74), sepsis (aOR, 1.60; 95% CI, 1.04–2.46), pneumonia (aOR, 2.54; 95% CI, 1.72–3.74), and acute kidney injury (aOR, 1.71; 95% CI, 1.24–2.35). Subgroup analyses revealed consistent associations between iron-deficiency anemia and prolonged LOS across age, sex, and obesity status categories.
Conclusion
In patients undergoing hepatic resection for CRLM, iron-deficiency anemia is an independent risk factor for prolonged LOS, unfavorable discharge, and several critical postoperative complications. These findings underscore the need for proactive anemia management to optimize surgical outcomes.

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