1.6-Gingerol Induced Apoptosis and Cell Cycle Arrest in Glioma Cells via MnSOD and ERK Phosphorylation Modulation
Sher-Wei LIM ; Wei-Chung CHEN ; Huey-Jiun KO ; Yu-Feng SU ; Chieh-Hsin WU ; Fu-Long HUANG ; Chien-Feng LI ; Cheng Yu TSAI
Biomolecules & Therapeutics 2025;33(1):129-142
6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.
2.6-Gingerol Induced Apoptosis and Cell Cycle Arrest in Glioma Cells via MnSOD and ERK Phosphorylation Modulation
Sher-Wei LIM ; Wei-Chung CHEN ; Huey-Jiun KO ; Yu-Feng SU ; Chieh-Hsin WU ; Fu-Long HUANG ; Chien-Feng LI ; Cheng Yu TSAI
Biomolecules & Therapeutics 2025;33(1):129-142
6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.
3.6-Gingerol Induced Apoptosis and Cell Cycle Arrest in Glioma Cells via MnSOD and ERK Phosphorylation Modulation
Sher-Wei LIM ; Wei-Chung CHEN ; Huey-Jiun KO ; Yu-Feng SU ; Chieh-Hsin WU ; Fu-Long HUANG ; Chien-Feng LI ; Cheng Yu TSAI
Biomolecules & Therapeutics 2025;33(1):129-142
6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.
4.Comparison of short-term clinical efficacy between CO external fixation and internal fixation with steel plate in the treatment of unstable distal radius fractures.
Min-Rui FU ; Chang-Long SHI ; Yong-Zhong CHENG ; Ming-Ming MA ; Zheng-Lin NIU ; Hai-Xiang SUN ; Jing-Hua GAO ; Zhong-Kai WU ; Yi-Ming XU
China Journal of Orthopaedics and Traumatology 2025;38(1):10-17
OBJECTIVE:
To evaluate the short-term clinical efficacy of external fixation and internal fixation with steel plate in the treatment of unstable distal radius fractures (AO-23C type), based on the principles of Chinese osteosynthesis (CO).
METHODS:
Forty-eight patients with unstable distal radius fractures between January 2022 and February 2023 were retrospectively analyzed and divided into the CO external fixation group and internal fixation group. CO external fixation group consisted of 25 patients, including 7 males and 18 females, aged from 37 to 56 years old with an average of ( 52.6±11.3) years old. Among them, there were 7 patients of traffic accidents and 18 patients of falls, resulting in a total of 25 patients of closed fractures and no open fractures, the treatment was conducted using closed reduction and CO external fixation. The internal fixation group consisted of 23 patients, comprising 8 males and 15 females, age ranged from 41 to 59 years old, with an average age of(53.3±13.7) years old. Among them, 8 patients resulted from car accidents while the remaining 15 patients were caused by falls. All 23 patients were closed fractures without any open fractures observed. The technique of open reduction and internal fixation with steel plate was employed. The perioperative data, including injury-operation time, operation duration, blood loss, and length of hospital stay, were assessed in both groups. Additionally, the QuickDASH score and visual analogue scale (VAS) were evaluated. Range of motion and grip strength assessment, imaging findings such as palmar inclination angle, ulnar declination angle, radius length, articular surface step, intra-articular space measurements were also examined along with any complications.
RESULTS:
The follow-up duration ranged from 0 to 24 months, with an average duration of (16.0±3.8) months. The CO external fixation exhibited significantly shorter time from injury to operation (2.4±3.3) d vs (7.4±3.7) d, shorter operation duration (56.27±15.23) min vs (74.10±5.26) min, lower blood loss (14.52±6.54) ml vs (32.32±10.03) ml, and reduced hospitalization days (14.04±3.24 )d vs (16.45±3.05) d compared to the internal fixation group (P<0.05). The QuickDASH score at 12 months post-operation was (8.21±1.64) in the CO external fixation group, while no significant difference was observed in the internal fixation group (7.04±3.64), P>0.05. There were no statistically significant differences in VAS between two groups at 6 weeks, as well as 1 and 3 months post-surgery (P>0.05). Additionally, there were no significant disparities observed in terms of range of motion and grip strength between two groups at the 2-year follow-up after the operation (P>0.05). After 12 months of surgery, the CO external fixation group exhibited a significantly smaller palmar inclination angle (17.90±2.18) ° vs (19.87±3.21) °, reduced articular surface step (0.11±0.03) mm vs (0.17±0.02) mm, and shorter radius length (8.16±1.11) mm compared to the internal fixation group (9.59±1.02) mm, P<0.05. The ulnar deviation angle and intra-articular space did not show any significant difference between two groups (P>0.05). The reduced fell within the allowable range between the CO external fixation group (23 out of 25 cases) and the internal fixation group (21 out of 23 cases) was not statistically significant (P=0.29). There was no significant difference in complications between the two groups(P>0.05).
CONCLUSION
Both the CO external fixation and open reduction with plate internal fixation demonstrate clinical efficacy in managing unstable distal radius fractures. The CO external fixation offers advantages in shorter injury-to-operation times, reduced intraoperative blood loss, and decreased surgical durations, while radial shortening is more effectively controlled by internal fixation.
Humans
;
Male
;
Female
;
Middle Aged
;
Radius Fractures/physiopathology*
;
Adult
;
Bone Plates
;
Fracture Fixation, Internal/methods*
;
External Fixators
;
Retrospective Studies
;
Fracture Fixation/methods*
;
Wrist Fractures
5.Experts consensus on standard items of the cohort construction and quality control of temporomandibular joint diseases (2024)
Min HU ; Chi YANG ; Huawei LIU ; Haixia LU ; Chen YAO ; Qiufei XIE ; Yongjin CHEN ; Kaiyuan FU ; Bing FANG ; Songsong ZHU ; Qing ZHOU ; Zhiye CHEN ; Yaomin ZHU ; Qingbin ZHANG ; Ying YAN ; Xing LONG ; Zhiyong LI ; Yehua GAN ; Shibin YU ; Yuxing BAI ; Yi ZHANG ; Yanyi WANG ; Jie LEI ; Yong CHENG ; Changkui LIU ; Ye CAO ; Dongmei HE ; Ning WEN ; Shanyong ZHANG ; Minjie CHEN ; Guoliang JIAO ; Xinhua LIU ; Hua JIANG ; Yang HE ; Pei SHEN ; Haitao HUANG ; Yongfeng LI ; Jisi ZHENG ; Jing GUO ; Lisheng ZHAO ; Laiqing XU
Chinese Journal of Stomatology 2024;59(10):977-987
Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.
6.Discussion on Li Fazhi's medication law in the treatment of cough based on data mining
Cheng FU ; Ye PAN ; Meng LI ; Long MA ; Yuying PAN ; Mingli ZHANG ; Fazhi LI
International Journal of Traditional Chinese Medicine 2024;46(7):920-925
Objective:To analyze the medication law of Professor Li Fazhi in the prescriptions for the treatment of cough; To explore his academic thoughts.Methods:Medical cases of Professor Li about the treatment for cough from January 1, 2015 to October 31, 2022 were collected. Excel2016 and R language 4.2.1 were used to conduct multidimensional analysis on property and taste, and meridians of drugs. High-frequency efficacy classification was explored through factor analysis, clustering analysis was conducted to distinguish drug groups, and time-lapse analysis on proportion and meridian was conducted on high-frequency drugs.Results:4 746 prescriptions involved 270 kinds of Chinese materia medica, with a total frequency of 57 700 times. The most common property and taste was warm, followed by cold. Warm medicines were mainly pungent warm and cold warm, and cold medicines were mainly pungent cold, sweet cold and bitter cold, and the main meridians were lung, spleen, stomach, and liver meridians. The top 35 kinds of Chinese materia medica with frequency could be clustered into 9 groups. Group 1: Perillae Fructus, Armeniacae Semen Amarum and Ephedrae Herba; group 2: Magnoliae Flosmagnoliae Flos, Cicadae Periostracum and Glycyrrhizae Radix et Rhizoma; group 3: Peucedani Radix, Platycodonis Radix, Mori Cortex, Schizonepetae Herba, Saposhnikoviae Radix and Farfarae Flos; group 4: Angelicae Dahuricae Radix, Notopterygii Rhizoma et Radix, Citri Reticulatae Pericarpium, Astragali Radix, Cimicifugae Rhizoma and Coptidis Rhizoma; group 5: Coicis Semen, Phragmitis Rhizoma, Persicae Semen and Benincasae Semen; group 6: Perillae Folium; group 7: Bupleuri Radix, Mume Fructus, Aurantii Fructus Immaturus, Scutellariae Radix and Paeoniae Radix Alba; group 8: Asari Radix et Rhizoma, Cinnamomi Ramulus, Zingiberis Rhizoma, Schisandrae Chinensis Fructus and Pinelliae Rhizoma Praeparatum cum Alumine; group 9: Poria and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle. The time-lapse analysis showed that the proportion of drugs used in the past three years such as Glycyrrhizae Radix et Rhizoma Praeparata cum Melle, Poria and Aurantii Fructus was gradually increasing.Conclusions:Professor Li's treatment of cough focuses on the lungs, spleen, and stomach. Clinical medication emphasizes the combination of ascending and descending factors, as well as the use of cold and warm. In recent years, there has been a greater emphasis on treating cough from the middle energizer.
7.Clinical Features and Prognosis of Patients with CD5+Diffuse Large B-Cell Lymphoma
Xiu-Juan HUANG ; Jian YANG ; Xiao-Fang WEI ; Yuan FU ; Yang-Yang ZHAO ; Ming-Xia CHENG ; Qing-Fen LI ; Hai-Long YAN ; You-Fan FENG
Journal of Experimental Hematology 2024;32(3):750-755
Objective:To analyze the clinical characteristics and prognosis of patients with CD5+diffuse large B-cell lymphoma(DLBCL).Methods:The clinical data of 161 newly treated DLBCL patients in Gansu Provincial Hospital from January 2013 to January 2020 were retrospectively analyzed.According to CD5 expression,the patients were divided into CD5+group and CD5-group.The clinical characteristics and prognosis of the two groups were statistically analyzed.Results:The median age of patients in CD5+group was 62 years,which was higher than 56 years in CD5-group(P=0.048).The proportion of women in CD5+group was 62.96%,which was significantly higher than 41.79%in CD5-group(P=0.043).The proportion of patients with IPI score>2 in CD5+group was 62.96%,which was higher than 40.30%in CD5-group(P=0.031).Survival analysis showed that the median overall survival and progression-free survival time of patients in CD5+group were 27(3-77)and 31(3-76)months,respectively,which were both shorter than 30(5-84)and 32.5(4-83)months in CD5-group(P=0.047,P=0.026).Univariate analysis showed that advanced age,positive CD5 expression,triple or double hit at initial diagnosis,high IPI score and no use of rituximab during chemotherapy were risk factors for the prognosis of DLBCL patients.Further Cox multivariate regression analysis showed that these factors were also independent risk factors except for advanced age.Conclusion:CD5+DLBCL patients have a worse prognosis than CD5-DLBCL patients.Such patients are more common in females,with advanced age and high IPI score,which is a special subtype of DLBCL.
8.Analysis of risk factors for contrast agent extravasation in coronary CT angiography
Haihong LONG ; Fei HAN ; Liangying GAN ; Zhuo LIU ; Jin CHENG ; Chao SUN ; Ling FU
China Medical Equipment 2024;21(9):97-101
Objective:To analyze the influencing factors of contrast agent extravasation in coronary CT angiography(CTA)examination,and to formulate intervention measures.Methods:A retrospective selection of data from 583 patients who underwent coronary CTA at Peking University People's Hospital from January to December 2023 was conducted.Logistic regression was used to analyze the patients'general information and injection protocols,and the risk factors of contrast agent extravasation were determined.Results:Among the 583 patients included,11 patients had contrast agent extravasation during CTA examination,with an extravasation rate of 1.887%.The contrast agent was all extravasated into the subcutaneous tissue,and the CT value did not reach the trigger criteria.Gender,education level,diabetes mellitus,history of intravenous chemotherapy,age,weight,body mass index(BMI),injection rate and injection dose were all associated with the occurrence of contrast agent extravasation,the difference was statistically significant(x2=18.911,7.563,16.567,4.279,t=3.576,3.244,1.865,4.297,6.532,P<0.05).Age,education level,history of intravenous chemotherapy,diabetes mellitus,injection rate and injection dose were risk factors for contrast agent extravasation in coronary CTA(OR=1.008,1.372,1.029,5.092,0.975,1.421,P<0.05).Conclusion:Factors such as low education level,advanced age,history of intravenous chemotherapy,high injection rate and large injection dose can increase the risk of contrast agent extravasation in coronary CTA examination.Radiology staff should closely monitor high-risk patients,strengthen monitoring of intravenous injection of contrast agents for coronary CTA examination,and reduce the occurrence of contrast agent extravasation.
9.Quality standard for Zhujieshen Formula Granules based on standard decoction
Chen-Hui YE ; Hai-Ming TANG ; Cheng-Fu YUAN ; Jia-Long GUO ; Ji-Hong ZHANG ; Ding YUAN ; Yu-Min HE
Chinese Traditional Patent Medicine 2024;46(9):2863-2869
AIM To establish the quality standard of the zhujieshen Formula Granules based on standard decoction.METHODS The contents and transfer rates of ginsenoside Ro and chikusetsu saponin Ⅳa in standard decoction and formula granules were determined by HPLC,after which the transfer rates were calculated.The HPLC characteristic chromatograms of standard decoctions were established,after which cluster analysis and principal component analysis were adopted.Then the HPLC characteristic chromatograms of formula granules were established.RESULTS Nine common peaks were found in the HPLC characteristic chromatograms of seventeen batches of standard decoctions with the similarities of more than 0.9(except for S6,S12),which were clustered into two categories,and the accumulative variance contribution rate of three principal components reached 86.7%.The contents of ginsenoside Ro in three batches of formula granules were 83.1-88.6 mg/g,and the transfer rates were 53.1%-55.5%.The contents of chikusetsusaponin Ⅳa were 14.8-15.0 mg/g,and the transfer rates were 47.4%-48.1%.Nine common peaks were found in the HPLC characteristic chromatograms of three batches of formula granules with the similarities of 0.998,0.998 and 0.999,respectively.CONCLUSION This reasonable and reliable method can comprehensively evaluate the quality of Zhujieshen Formula Granules,and provide a reference for the quality control.
10.Artificial intelligence predicts direct-acting antivirals failure among hepatitis C virus patients: A nationwide hepatitis C virus registry program
Ming-Ying LU ; Chung-Feng HUANG ; Chao-Hung HUNG ; Chi‐Ming TAI ; Lein-Ray MO ; Hsing-Tao KUO ; Kuo-Chih TSENG ; Ching-Chu LO ; Ming-Jong BAIR ; Szu-Jen WANG ; Jee-Fu HUANG ; Ming-Lun YEH ; Chun-Ting CHEN ; Ming-Chang TSAI ; Chien-Wei HUANG ; Pei-Lun LEE ; Tzeng-Hue YANG ; Yi-Hsiang HUANG ; Lee-Won CHONG ; Chien-Lin CHEN ; Chi-Chieh YANG ; Sheng‐Shun YANG ; Pin-Nan CHENG ; Tsai-Yuan HSIEH ; Jui-Ting HU ; Wen-Chih WU ; Chien-Yu CHENG ; Guei-Ying CHEN ; Guo-Xiong ZHOU ; Wei-Lun TSAI ; Chien-Neng KAO ; Chih-Lang LIN ; Chia-Chi WANG ; Ta-Ya LIN ; Chih‐Lin LIN ; Wei-Wen SU ; Tzong-Hsi LEE ; Te-Sheng CHANG ; Chun-Jen LIU ; Chia-Yen DAI ; Jia-Horng KAO ; Han-Chieh LIN ; Wan-Long CHUANG ; Cheng-Yuan PENG ; Chun-Wei- TSAI ; Chi-Yi CHEN ; Ming-Lung YU ;
Clinical and Molecular Hepatology 2024;30(1):64-79
Background/Aims:
Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy.
Methods:
We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment.
Results:
The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset.
Conclusions
Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

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