1.Mebendazole effectively overcomes imatinib resistance by dualtargeting BCR/ABL oncoprotein and ββ-tubulin in chronic myeloid leukemia cells
Li YANG ; Zhuanyun DU ; Yuhang PENG ; Wenyao ZHANG ; Wenli FENG ; Ying YUAN
The Korean Journal of Physiology and Pharmacology 2025;29(1):67-81
To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.
2.Mebendazole effectively overcomes imatinib resistance by dualtargeting BCR/ABL oncoprotein and ββ-tubulin in chronic myeloid leukemia cells
Li YANG ; Zhuanyun DU ; Yuhang PENG ; Wenyao ZHANG ; Wenli FENG ; Ying YUAN
The Korean Journal of Physiology and Pharmacology 2025;29(1):67-81
To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.
3.Mebendazole effectively overcomes imatinib resistance by dualtargeting BCR/ABL oncoprotein and ββ-tubulin in chronic myeloid leukemia cells
Li YANG ; Zhuanyun DU ; Yuhang PENG ; Wenyao ZHANG ; Wenli FENG ; Ying YUAN
The Korean Journal of Physiology and Pharmacology 2025;29(1):67-81
To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.
4.Mebendazole effectively overcomes imatinib resistance by dualtargeting BCR/ABL oncoprotein and ββ-tubulin in chronic myeloid leukemia cells
Li YANG ; Zhuanyun DU ; Yuhang PENG ; Wenyao ZHANG ; Wenli FENG ; Ying YUAN
The Korean Journal of Physiology and Pharmacology 2025;29(1):67-81
To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.
5.Mebendazole effectively overcomes imatinib resistance by dualtargeting BCR/ABL oncoprotein and ββ-tubulin in chronic myeloid leukemia cells
Li YANG ; Zhuanyun DU ; Yuhang PENG ; Wenyao ZHANG ; Wenli FENG ; Ying YUAN
The Korean Journal of Physiology and Pharmacology 2025;29(1):67-81
To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.
6.Shexiang Tongxin Dropping Pill Improves Stable Angina Patients with Phlegm-Heat and Blood-Stasis Syndrome: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.
Ying-Qiang ZHAO ; Yong-Fa XING ; Ke-Yong ZOU ; Wei-Dong JIANG ; Ting-Hai DU ; Bo CHEN ; Bao-Ping YANG ; Bai-Ming QU ; Li-Yue WANG ; Gui-Hong GONG ; Yan-Ling SUN ; Li-Qi WANG ; Gao-Feng ZHOU ; Yu-Gang DONG ; Min CHEN ; Xue-Juan ZHANG ; Tian-Lun YANG ; Min-Zhou ZHANG ; Ming-Jun ZHAO ; Yue DENG ; Chang-Jiang XIAO ; Lin WANG ; Bao-He WANG
Chinese journal of integrative medicine 2025;31(8):685-693
OBJECTIVE:
To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents.
METHODS:
This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs).
RESULTS:
This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed.
CONCLUSION
STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans
;
Double-Blind Method
;
Drugs, Chinese Herbal/adverse effects*
;
Male
;
Female
;
Middle Aged
;
Angina, Stable/physiopathology*
;
Aged
;
Syndrome
;
Treatment Outcome
;
Placebos
;
Tablets
7.Inhibition of KLK8 promotes pulmonary endothelial repair by restoring the VE-cadherin/Akt/FOXM1 pathway.
Ying ZHAO ; Hui JI ; Feng HAN ; Qing-Feng XU ; Hui ZHANG ; Di LIU ; Juan WEI ; Dan-Hong XU ; Lai JIANG ; Jian-Kui DU ; Ping-Bo XU ; Yu-Jian LIU ; Xiao-Yan ZHU
Journal of Pharmaceutical Analysis 2025;15(4):101153-101153
Image 1.
8.Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine.
Xin-Ran DU ; Meng-Yi WU ; Mao-Can TAO ; Ying LIN ; Chao-Ying GU ; Min-Feng WU ; Yi CAO ; Da-Can CHEN ; Wei LI ; Hong-Wei WANG ; Ying WANG ; Yi WANG ; Han-Zhi LU ; Xin LIU ; Xiang-Fei SU ; Fu-Lun LI
Journal of Integrative Medicine 2025;23(6):641-653
Traditional Chinese medicine (TCM) is a well-accepted therapy for atopic dermatitis (AD). However, there are currently no evidence-based guidelines integrating TCM and Western medicine for the treatment of AD, limiting the clinical application of such combined approaches. Therefore, the China Association of Chinese Medicine initiated the development of the current guideline, focusing on key issues related to the use of TCM in the treatment of AD. This guideline was developed in accordance with the principles of the guideline formulation manual published by the World Health Organization. A comprehensive review of the literature on the combined use of TCM and Western medicine to treat AD was conducted. The findings were extensively discussed by experts in dermatology and pharmacy with expertise in both TCM and Western medicine. This guideline comprises 23 recommendations across seven major areas, including TCM syndrome differentiation and classification of AD, principles and application scenarios of TCM combined with Western medicine for treating AD, outcome indicators for evaluating clinical efficacy of AD treatment, integration of TCM pattern classification and Western medicine across disease stages, daily management of AD, the use of internal TCM therapies and proprietary Chinese medicines, and TCM external treatments. Please cite this article as: Du XR, Wu MY, Tao MC, Lin Y, Gu CY, Wu MF, Cao Y, Chen DC, Li W, Wang HW, Wang Y, Wang Y, Lu HZ, Liu X, Su XF, Li FL. Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine. J Integr Med. 2025; 23(6):641-653.
Dermatitis, Atopic/drug therapy*
;
Humans
;
Medicine, Chinese Traditional/methods*
;
Integrative Medicine
;
Drugs, Chinese Herbal/therapeutic use*
;
Practice Guidelines as Topic
9.Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine: Threatened Abortion
Xinchun YANG ; Shuyu WANG ; Huilan DU ; Songping LUO ; Zhe JIN ; Rong LI ; Xiangyan RUAN ; Qin ZHANG ; Xiaoling FENG ; Shicai CHEN ; Fengjie HE ; Shaobin WEI ; Qun LU ; Yanqin WANG ; Yang LIU ; Qingwei MENG ; Zengping HAO ; Ying LI ; Mei MO ; Xiaoxiao ZHANG ; Ruihua ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):241-246
Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine (TCM). The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology, Western medicine obstetrics and gynecology, and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion, the experts concluded that chromosome, endocrine, and immune abnormalities were the key factors for the occurrence of threatened abortion, and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion, TCM has advantages in preventing miscarriages, alleviating clinical symptoms and TCM syndromes, relieving anxiety, regulating reproductive endocrine and immune abnormalities, personalized and diversified treatment, enhancing efficiency and reducing toxicity, and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.
10.A prospective study on objective assessment of perineal lacerations
Ying FENG ; Xu XIE ; Hui DU ; Mingwei LI ; Qintian ZHENG
Chinese Journal of Perinatal Medicine 2024;27(11):885-892
Objective:To systematically observe the location and severity of perineal lacerations during childbirth and explore the relationship between the length/depth and the degrees of perineal lacerations.Methods:This prospective study recruited full-term singleton cephalic pregnant women planning vaginal delivery at the Fourth Hospital of Shijiazhuang from March 2023 to July 2023. Before the second stage of labor, the perineal body length (PBL) was measured. After delivery, the locations of all birth canal lacerations, the perineal skin lacerations length (PSLL), and the perineal lacerations depth (PLD) were measured and recorded. A magnifying glass was used to identify the layers of the skin and photographs were taken if necessary. Statistical methods such as t-test, rank-sum test, and Chi-square test (or Fisher's exact test) were used to compare the basic conditions and birth canal lacerations between primiparous and multiparous women. The receiver operating characteristic (ROC) curve was used to analyze the sensitivity and specificity of PSLL, PLD, and the PSLL/PBL ratio. Results:During the study period, 200 women were included, of which 189 had vaginal deliveries (173 primiparous and 16 multiparous) and 11 had emergency cesarean sections (10 primiparous and one multiparous). Among the 173 primiparous women with vaginal deliveries, 33 (19.1%) underwent episiotomy, and the other 140 (80.9%) had perineal lacerations. Among these cases of perineal lacerations, nine were complicated by vaginal wall lacerations, 20 by labial lacerations, and four by clitoral and urethral lacerations. There were 32 (22.9%) primiparous women with first-degree perineal lacerations and 108 (77.1%) with second-degree perineal lacerations. Among the 16 multiparous women who delivered vaginally, two had intact birth canals without lacerations, and 14 had perineal lacerations (eight with first-degree and six with second-degree perineal lacerations). Besides, none of them underwent episiotomy or assisted vaginal delivery. The rates of episiotomy and second-degree perineal lacerations were higher in primiparous women than in multiparous women [19.1% (33/173) vs. 0/16, 77.1% (108/173) vs. 6/14, Fisher's exact test, both P<0.05). The PSLL, PLD, and PSLL/PBL ratio were significantly lower in the primiparous women with first-degree perineal lacerations than in the primiparous women with second-degree perineal lacerations [0.0 mm (0.0-10.0 mm) vs. 30.0 mm (25.5-40.0 mm), 5.0 mm (1.5-10.0 mm) vs. 14.0 mm (10.0-15.0 mm), 0.0 mm (0.0-21.1 mm) vs. 63.6 mm (50.0-77.3 mm); Z values were-8.04,-6.46, and-7.75, respectively, all P<0.05]. The optimal cut-off values of PSLL, PLD, and PSLL/PBL ratio for differentiating between first-degree and second-degree perineal lacerations were 15 mm, 9 mm, and 33.33%, with the area under the ROC curve (AUC) of 0.965, 0.869, and 0.951 and the sensitivity of 91.67%, 91.67%, and 89.81%, respectively. The AUC of PSLL was significantly greater than that of PLD ( Z=2.55, P=0.011), but the AUC of PSLL/PBL ratio showed no significant difference with that of PSLL or PLD ( Z=1.18 and 1.89, both P>0.05). Conclusions:It is difficult for full-term primiparas to maintain perineal integrity during vaginal delivery. Measuring the PSLL, PLD, and PSLL/PBL ratio of primiparous women will be useful for distinction between first- and second-degree perineal lacerations.

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