1.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.
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.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.
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.Application of colloidal gold method and chemiluminescence method for detecting gonadotropins in morning urine to assess pubertal development status in children.
Xue-Qi ZHAO ; Wen-Li LU ; Wen-Ying LI ; Jun-Qi WANG ; Zhi-Ya DONG ; Yuan XIAO ; Xiao-Fei ZHANG ; Li JIANG ; Xiao-Yu MA
Chinese Journal of Contemporary Pediatrics 2025;27(2):199-204
OBJECTIVES:
To explore the application of the colloidal gold method and chemiluminescence method in detecting gonadotropin (Gn) in morning urine for assessing pubertal development status in children.
METHODS:
A total of 132 children diagnosed with central precocious puberty (CPP), early and fast puberty (EFP), and premature thelarche (PT) at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from November 2021 to December 2022 were included, along with 685 healthy children who underwent routine health examinations at the hospital's pediatric health care department during the same period. All 132 patients underwent a gonadotropin-releasing hormone (GnRH) stimulation test. Both patients and healthy children had their urinary Gn levels measured using the colloidal gold method and chemiluminescence method, including levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The correlation between serum Gn and urinary Gn detected by the two methods, as well as the correlation between Tanner stages of healthy children and urinary Gn, was analyzed.
RESULTS:
Urine Gn levels detected by both the colloidal gold method and chemiluminescence method showed a positive correlation with serum LH baseline values, LH peak values, baseline LH/FSH ratios, and peak LH/FSH ratios (P<0.05). In healthy children, urinary LH levels detected by the chemiluminescence method gradually increased from Tanner stage Ⅰ to Ⅳ (P<0.05), while urinary FSH levels were lower in Tanner stage I than in stages Ⅱ, Ⅲ, and IV (P<0.05). Urinary LH levels detected by the colloidal gold method were lower in Tanner stage I compared to stages Ⅱ, Ⅲ, and IV, with the highest levels observed in Tanner stage Ⅳ (P<0.05). Additionally, urinary FSH levels in Tanner stage Ⅲ were higher than in stages Ⅰ and Ⅱ (P<0.05). The area under the receiver operating characteristic curve for evaluating Tanner stages I and II in healthy children using urinary LH and FSH levels by the chemiluminescence method and urinary LH levels by the colloidal gold method were 0.730, 0.699, and 0.783, respectively.
CONCLUSIONS
The colloidal gold method and chemiluminescence method for detecting Gn in morning urine show good correlation with serum Gn levels. As a non-invasive and convenient detection method, the colloidal gold method can serve as a useful tool for screening the onset of pubertal development in children.
Humans
;
Child
;
Male
;
Female
;
Gold Colloid
;
Luminescent Measurements/methods*
;
Gonadotropins/urine*
;
Puberty
;
Luteinizing Hormone/urine*
;
Child, Preschool
;
Adolescent
;
Follicle Stimulating Hormone/urine*
6.Expression and Clinical Significance of CaMKIIγ in Patients with Acute Myeloid Leukemia.
Ming-Kai LIU ; Xu DAI ; Xiao-Ying ZHAO ; Wei-Wei ZHENG ; Ya-Jing MA
Journal of Experimental Hematology 2025;33(3):726-732
OBJECTIVE:
To investigate the expression and potential mechanism of calcium/calmodulin-dependent protein kinase II gamma (CaMKIIγ) in patients with acute myeloid leukemia (AML).
METHODS:
Peripheral blood samples were collected from 90 AML patients, and mononuclear cells were isolated. The expression of CaMKIIγ was measured using real-time quantitative PCR and Western blot. The diagnostic value of CaMKIIγ for AML was assessed, and its correlation with clinical characteristics was analyzed using the clinical data of patients. Additionally, the molecular mechanisms of CaMKIIγ were preliminarily explored.
RESULTS:
Compared with the control group, the expression of CaMKIIγ was significantly upregulated in AML patients. Receiver operating characteristic (ROC) curve analysis showed that CaMKIIγ could serve as a promising biomarker for distinguishing AML patients from healthy individuals. Furthermore, CaMKIIγ was significantly correlated with white blood cell (WBC) count and FLT3-ITD mutation. CaMKIIγ was highly expressed in both newly diagnosed and relapsed AML patients, while decreased during remission. In AML cell lines, the expression levels of CaMKIIγ were all elevated. Inhibition of phosphorylated CaMKIIγ by berbamine led to a decrease in pAKT and pSTAT5 expression.
CONCLUSION
CaMKIIγ is significantly upregulated in AML patients, and is associated with poor clinicopathological features and unfavorable prognosis. It may serve as a prognostic marker and potential therapeutic target in AML. Its expression may be related to the activation of pAKT and pSTAT5, suggesting that CaMKIIγ may contribute to the development and progression of AML through the activation of the AKT/STAT5 signaling pathway.
Humans
;
Leukemia, Myeloid, Acute/metabolism*
;
Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism*
;
STAT5 Transcription Factor/metabolism*
;
Male
;
Female
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Mutation
;
Middle Aged
;
Adult
;
Clinical Relevance
7.Postdischarge cancer and mortality in patients with coronary artery disease: a retrospective cohort study.
Yi-Hao WANG ; Shao-Ning ZHU ; Ya-Wei ZHAO ; Kai-Xin YAN ; Ming-Zhuang SUN ; Zhi-Jun SUN ; Yun-Dai CHEN ; Shun-Ying HU
Journal of Geriatric Cardiology 2025;22(6):578-586
BACKGROUND:
Our understanding of the correlation between postdischarge cancer and mortality in patients with coronary artery disease (CAD) remains incomplete. The aim of this study was to investigate the relationships between postdischarge cancers and all-cause mortality and cardiovascular mortality in CAD patients.
METHODS:
In this retrospective cohort study, 25% of CAD patients without prior cancer history who underwent coronary artery angiography between January 1, 2011 and December 31, 2015, were randomly enrolled using SPSS 26.0. Patients were monitored for the incidence of postdischarge cancer, which was defined as cancer diagnosed after the index hospitalization, survival status and cause of death. Cox regression analysis was used to explore the association between postdischarge cancer and all-cause mortality and cardiovascular mortality in CAD patients.
RESULTS:
A total of 4085 patients were included in the final analysis. During a median follow-up period of 8 years, 174 patients (4.3%) developed postdischarge cancer, and 343 patients (8.4%) died. A total of 173 patients died from cardiovascular diseases. Postdischarge cancer was associated with increased all-cause mortality risk (HR = 2.653, 95% CI: 1.727-4.076, P < 0.001) and cardiovascular mortality risk (HR = 2.756, 95% CI: 1.470-5.167, P = 0.002). Postdischarge lung cancer (HR = 5.497, 95% CI: 2.922-10.343, P < 0.001) and gastrointestinal cancer (HR = 1.984, 95% CI: 1.049-3.750, P = 0.035) were associated with all-cause mortality in CAD patients. Postdischarge lung cancer was significantly associated with cardiovascular death in CAD patients (HR = 4.979, 95% CI: 2.114-11.728, P < 0.001), and cardiovascular death was not significantly correlated with gastrointestinal cancer or other types of cancer.
CONCLUSIONS
Postdischarge cancer was associated with all-cause mortality and cardiovascular mortality in CAD patients. Compared with other cancers, postdischarge lung cancer had a more significant effect on all-cause mortality and cardiovascular mortality in CAD patients.
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.Clinical and pathological characteristics of adrenal cortical carcinoma:a single-center retrospective study
Qing-Zheng WU ; Ming-Xiu YANG ; Bing LI ; Shu-Ying LI ; Zi-Xin GUO ; Yi-Jun LI ; Ya-Qi YIN ; Ya-Jing WANG ; Kang CHEN ; Li ZANG ; Wei-Jun GU ; Yi-Ming MU ; Zhao-Hui LYU
Medical Journal of Chinese People's Liberation Army 2025;50(7):786-792
Objective To investigate the clinical and pathological characteristics of adrenal cortical carcinoma(ACC),compare differences between hypercortisolism and non-functional ACC,and assess the diagnostic value of indicators such as Ki-67 index.Methods The clinical data of 57 ACC patients admitted to the First Medical Center of Chinese PLA General Hospital from January 2015 to March 2025 were retrospectively analyzed.According to the results of endocrine function assessment,47 of these patients were divided into hypercortisolism group(n=19)and non-functional group(n=28).The differences in clinical and pathological characteristics between the two groups were compared,and non-parametric tests and Spearman correlation analysis were used to explore the relationship between Ki-67 index and tumor stage as well as imaging features.Results Among the 57 patients,there were 20 males and 37 females,with a male-to-female ratio of 1:1.85.The age ranged from 16 to 76 years,and the age at diagnosis was(48.7±13.3)years.The tumor diameter was(10.53±4.14)cm.The tumors were located on the right side in 12 cases(21.1%),on the left side in 34 cases(59.6%),and bilaterally in 11 cases(19.3%).Among them,16 cases(28.1%)were complicated with glucose metabolism disorders,31 cases(54.3%)had hypertension,and 20 cases(35.1%)had hypokalemia.According to ENSAT staging,there were 0 cases in stage Ⅰ,15 cases(26.3%)in stage Ⅱ,24 cases(42.1%)in stage Ⅲ,and 18 cases(31.6%)in stage Ⅳ.Endocrine function assessment was completed in 47 of the 57 patients,including 28 cases(59.6%)of non-functional ACC and 19 cases(40.4%)of hypercortisolism(including 1 case of hypercortisolism combined with increased sex hormone secretion).Compared with non-functional group,hypercortisolism group had a significantly higher prevalence of hypertension(P=0.014),later ENSAT stage(P=0.010),and a higher proportion of hypervascularization(P=0.048).The median Ki-67 index was 20%(10%-40%),showing no significant correlation with either the maximum tumor diameter or SUVmax value,but it was related to ENSAT staging,with Ki-67 index in stageⅣ patients being significantly higher than that in stage Ⅱ(P=0.032).Immunohistochemistry results showed that the positive rate of Inhibin-α was 84.8%,and the positive rate of Melan-A was 40.9%.Conclusions ACC is a rare malignant endocrine tumor.ACC patients with hypercortisolism are more likely to be complicated with hypertension,have later staging,and more common hypervascular manifestations.Clinically,their endocrine function should be prioritized for assessment,and more active treatment strategies should be adopted.Diagnosis should be combined with imaging characteristics(such as hypervascularization)and immunohistochemical indicators(Ki-67,Inhibin-α,Melan-A).The significant increase in Ki-67 is in the advanced stage can serve as an important prognostic indicator to guide individualized treatment.
10.The anti-heart failure mechanism of N-acetylcysteine in diabetic cardiomyopathy via ERK1/2 path-way
Jian JI ; Ya-hong HUANG ; Ying-min LU ; Dong-mei YUE ; Xiao-hui ZHENG ; Jin-chun ZHANG ; Zhao-xia WANG
Chinese Journal of cardiovascular Rehabilitation Medicine 2025;34(4):543-547
Objective:To investigate the anti-heart failure mechanism of N-acetylcysteine(NAC)in diabetic cardiomyop-athy independent from coronary artery factors.Methods:A total of 40 diabetic mice after heart failure model construction were randomly divided into two groups,NAC group(n=20,NAC 100mg·kg-1·d-1)and control group(n=20,Saline 100 mg·kg-1·d-1).Echocardiography was performed to detect left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),left ventricular ejection fraction(LVEF),mitral left ventricular early-dias-tolic peak flow velocity/left ventricular late-diastolic peak flow velocity(E/A),isovolumic relaxation time(IVRT)and cardiac output(CO)after 4 weeks.Terminal uridine nick-end labeling(TUNEL)was performed to detect apoptosis in-dex,and Western Blot was performed to detect the expression of extracellular regulated protein kinases(ERK)1/2 after 6 weeks in two groups.Results:Compared to those in control group,mice in NAC group had significant higher LVEF[(40.5±3.4)%vs.(36.9±3.2)%],E/A[(1.5±0.1)vs.(1.4±0.1)]and CO[(10.3±0.6)ml/min vs.(9.9±0.5)ml/min](P<0.05 or<0.01);and significant lower LVESV[(23.1±1.3)μl vs.(24.7±1.5)μl],apoptosis index[(31.2±0.5)%vs.(45.1±0.9)%]and the expression of ERK1/2[(2.2±0.2)vs.(3.9±0.1)](P<0.001 all).Conclusion:NAC exerts anti-heart failure effect by attenuating apoptosis of cardiomyocytes via regulating ERK1/2 pathway.

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