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.Effects and mechanism of Tianma xiongling zhixuan tablet on autophagy of vascular endothelial cells
Sunan YONG ; Chi FANG ; Yuanxiong LONG ; Ping LI ; Xiaobing XIE
China Pharmacy 2025;36(14):1737-1742
OBJECTIVE To explore the effects of Tianma xiongling zhixuan tablet on autophagy in vascular endothelial cells of rats and its potential mechanism. METHODS The rat aortic endothelial cells (RAECs) were divided into normal group, model group, blank serum group, traditional Chinese medicine (TCM) medicated serum group, autophagy blocker group, autophagy agonist group, and TCM combined with autophagy agonist group. Except for normal group, other groups were given 10 μg/mL lipopolysaccharide for 24 hours to induce RAECs inflammation injury model. Blank serum group was treated with 10% blank serum; TCM medicated serum group received 10% medicated serum derived from Tianma xiongling zhixuan tablet; autophagy blocker group was treated with 20 μmol/L of PD98059; autophagy agonist group was administered 50 μmol/L Honokiol. Lastly, the TCM combined with autophagy agonist group was given both 10% medicated serum derived from Tianma xiongling zhixuan tablet and 50 μmol/L Honokiol. The morphological characteristics of RAECs in each group were observed. The cell viability of each group, the contents of endothelin-1 (ET-1) and nitric oxide (NO), mitochondrial reactive oxygen species, mitochondrial membrane potential, and the expression levels of PTEN-induced kinase 1 (PINK1), Parkin, ubiquitin-binding protein (p62), and microtubule-associated protein 1 light chain 3 (LC3) were detected. RESULTS Compared with model group, the levels of ET-1, mitochondrial reactive oxygen species, and the relative expressions of PINK1, Parkin, and LC3 proteins in the autophagy blocker group and TCM medicated serum group were decreased or down-regulated significantly (P<0.05 or P<0.01); the cell viability rate (only autophagy blocker group), NO level, mitochondrial membrane potential, and the E-mail:46164660@qq.com relative expression level of p62 protein were increased or up-regulated significantly (P<0.05 or P<0.01); the pathological damage of RAECs was significantly improved, the number of cells increased significantly, and the typical paving stone-like characteristics were restored. The levels of ET-1, mitochondrial reactive oxygen species, and the relative expression levels of Parkin and LC3 proteins in the autophagy agonist group were increased or up-regulated significantly (P<0.05 or P<0.01), while cell viability rate was decreased significantly (P<0.05), the damage of RAECs was aggravated. Compared with the autophagy agonist group, the cell viability rate and the relative expression level of p62 protein in TCM combined autophagy agonist group were increased or up-regulated significantly (P<0.05 or P<0.01), while the levels of ET-1, the relative expression levels of PINK1, Parkin, and LC3 proteins were down-regulated significantly (P< 0.01), the damage of RAECs was reversed to a certain extent. CONCLUSIONS Tianma xiongling zhixuan tablet protects vascular endothelial function by regulating mitochondrial autophagy, the mechanism of which may be associated with the regulation of PINK1/Parkin signaling pathway and the inhibition of mitochondrial autophagy.
6.Research progress in mechanisms of herb pairs in treating ischemic stroke.
Shu ZHANG ; Chun-Long RAN ; Chi-Yuan MA ; Xiang-Zhe LIU
China Journal of Chinese Materia Medica 2025;50(8):2041-2049
Ischemic stroke(IS) is a complex pathological process involving multiple cellular and molecular mechanisms and it is characterized by high mortality, high disability, and high recurrence. In recent years, the incidence of IS in China has been increasing year by year, and it has a trend of occurring in increasingly young individuals. Herb pairs are the smallest unit of traditional Chinese medicine(TCM) compatibility and an important part of TCM compounding, and the research on them is of great significance in guiding the clinical medication. Pharmacological studies have confirmed that certain herb pairs can exert anti-ischemic effects through various pathways such as reducing inflammation, alleviating oxidative stress, protecting the nervous system, and promoting neovascularization. By reviewing the relevant articles in the past decade, this paper probes into the combination rules, modern experimental studies, and combination ratios of the commonly used herb pairs from the etiology and pathogenesis of IS and summarizes 18 commonly used and deeply studied herb pairs, with a view to providing reference for the application, research, and development of clinical medicines.
Humans
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Drugs, Chinese Herbal/chemistry*
;
Animals
;
Ischemic Stroke/metabolism*
;
Medicine, Chinese Traditional
7.Genetic and clinical characteristics of children with RAS-mutated juvenile myelomonocytic leukemia.
Yun-Long CHEN ; Xing-Chen WANG ; Chen-Meng LIU ; Tian-Yuan HU ; Jing-Liao ZHANG ; Fang LIU ; Li ZHANG ; Xiao-Juan CHEN ; Ye GUO ; Yao ZOU ; Yu-Mei CHEN ; Ying-Chi ZHANG ; Xiao-Fan ZHU ; Wen-Yu YANG
Chinese Journal of Contemporary Pediatrics 2025;27(5):548-554
OBJECTIVES:
To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations.
METHODS:
A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022.
RESULTS:
A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05).
CONCLUSIONS
Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans
;
Leukemia, Myelomonocytic, Juvenile/therapy*
;
Mutation
;
Male
;
Female
;
Child, Preschool
;
Retrospective Studies
;
Child
;
Infant
;
GTP Phosphohydrolases/genetics*
;
Membrane Proteins/genetics*
;
Adolescent
;
Hematopoietic Stem Cell Transplantation
;
Proportional Hazards Models
;
Proto-Oncogene Proteins p21(ras)/genetics*
;
Prognosis
8.Large-scale salmonella outbreak associated with banh mi, Viet Nam, 2024
Tinh Huu Ho ; Phuong Hoai Hoang ; Lam Vo Thi Ngoc ; Minh Nguyen Dinh ; Dong Do Thanh ; Viet Nguyen Dinh ; O Phan Van ; Phuong Nguyen Thi Lan ; Thanh Nguyen Quoc ; Nhan Ho The ; Nhan Le Dinh Trong ; Chinh Van Dang
Western Pacific Surveillance and Response 2024;15(3):36-42
Objective: To investigate the cause of a foodborne outbreak that occurred in Dong Nai province, Viet Nam, in 2024, and implement control measures.
Methods: An initial investigation was conducted to confirm the outbreak, which was followed by epidemiological and environmental investigations to find the plausible causative food item. Clinical specimens and food samples were tested to identify the pathogen.
Results: A total of 547 symptomatic cases were recorded, of whom two were in severe condition requiring extracorporeal membrane oxygenation and ventilation, one of whom died. Among 99 interviewed cases, the mean incubation time was 9 hours (range 2–24 hours), with the main symptoms being fever, abdominal pain, diarrhoea and vomiting. All patients had eaten banh mi from a local bakery. Salmonella spp. were identified in food samples and clinical specimens. The bakery halted production, and the outbreak ended after 1 week.
Discussion: All the patients were exposed to only one food in common, which facilitated the investigation process. This outbreak is a reminder to small retailers and take-away shops of the importance of food safety management in preventing similar future outbreaks. All food handlers must comply with food hygiene principles, especially in hot temperatures, which boosts bacterial growth.
9.Aesthetic Investigation of the Pretarsal Shows and Morphology of Double Eyelids in Chinese Populations: A Questionnaire-based Survey
Yarong CHI ; Zhujun LI ; Lin JIN ; Nanze YU ; Jiuzuo HUANG ; Xiao LONG
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1334-1341
To explore the ideal pretarsal shows and morphological characteristics of double eyelids in Chinese populations through a morphometric analysis. This study employed a convenience sampling method to survey Chinese adults who did not reside abroad for an extended period (with cumulative overseas stay of over one year). From November 2023 to May 2024, electronic questionnaires were distributed to collect attractiveness ratings of nine different images (including one image featuring single eyelid and eight images with varying pretarsal shows and morphologies of double eyelids). Stratified comparisons were conducted based on gender, age, occupation, etc., to determine the ideal pretarsal show and morphology of double eyelids. Quantitative analysis was performed on the aesthetic features of the nine images depicting double eyelids to validate and elucidate the survey findings. A total of 493 questionnaires were filled out, and 397 valid questionnaires were included for data analysis after quality control. As for the whole cohort, the images feathering 2 mm double eyelid were deemed to be the most attractive, with the in-fold type scoring (3.72±0.97) points and the out-fold type scoring (3.65±1.04) points. The next was 1 mm, followed by 3 mm, single eyelid, and finally, 4 mm. As for morphology, in-fold type achieved higher scores than out-fold type in images with the same pretarsal show. However, statistically significant differences were only found in ratings for the images with 3 mm and 4 mm double eyelids (all This study validates that the pretarsal show of 2 mm and the presence of either an in-fold or out-fold morphology are considered optimal for double eyelids among Chinese individuals. These findings hold significant implications for the planning of double eyelid surgeries, assessment of surgical outcomes, and evaluation of other periocular procedures associated with double eyelid surgeries.
10.Aesthetic Investigation of the Pretarsal Shows and Morphology of Double Eyelids in Chinese Populations: A Questionnaire-based Survey
Yarong CHI ; Zhujun LI ; Lin JIN ; Nanze YU ; Jiuzuo HUANG ; Xiao LONG
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1334-1341
To explore the ideal pretarsal shows and morphological characteristics of double eyelids in Chinese populations through a morphometric analysis. This study employed a convenience sampling method to survey Chinese adults who did not reside abroad for an extended period (with cumulative overseas stay of over one year). From November 2023 to May 2024, electronic questionnaires were distributed to collect attractiveness ratings of nine different images (including one image featuring single eyelid and eight images with varying pretarsal shows and morphologies of double eyelids). Stratified comparisons were conducted based on gender, age, occupation, etc., to determine the ideal pretarsal show and morphology of double eyelids. Quantitative analysis was performed on the aesthetic features of the nine images depicting double eyelids to validate and elucidate the survey findings. A total of 493 questionnaires were filled out, and 397 valid questionnaires were included for data analysis after quality control. As for the whole cohort, the images feathering 2 mm double eyelid were deemed to be the most attractive, with the in-fold type scoring (3.72±0.97) points and the out-fold type scoring (3.65±1.04) points. The next was 1 mm, followed by 3 mm, single eyelid, and finally, 4 mm. As for morphology, in-fold type achieved higher scores than out-fold type in images with the same pretarsal show. However, statistically significant differences were only found in ratings for the images with 3 mm and 4 mm double eyelids (all This study validates that the pretarsal show of 2 mm and the presence of either an in-fold or out-fold morphology are considered optimal for double eyelids among Chinese individuals. These findings hold significant implications for the planning of double eyelid surgeries, assessment of surgical outcomes, and evaluation of other periocular procedures associated with double eyelid surgeries.


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