1.USP51/GRP78/ABCB1 axis confers chemoresistance through decreasing doxorubicin accumulation in triple-negative breast cancer cells.
Yang OU ; Kun ZHANG ; Qiuying SHUAI ; Chenyang WANG ; Huayu HU ; Lixia CAO ; Chunchun QI ; Min GUO ; Zhaoxian LI ; Jie SHI ; Yuxin LIU ; Siyu ZUO ; Xiao CHEN ; Yanjing WANG ; Mengdan FENG ; Hang WANG ; Peiqing SUN ; Yi SHI ; Guang YANG ; Shuang YANG
Acta Pharmaceutica Sinica B 2025;15(5):2593-2611
Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.
2.Acupuncture point selection for prevention and treatment of generalized anxiety disorder from the perspective of Microbiota-Gut-Brain Axis
Xiaxia JIN ; Leyao QIN ; Mengdan ZHANG ; Tao GAO ; Zhengquan LEI ; Feng ZHOU ; Wendi DONG
International Journal of Traditional Chinese Medicine 2023;45(1):8-12
Disorders of the gut flora (GF) affect the level of 5-hydroxytryptamine (5-HT) in the brain of patients with generalized anxiety disorder (GAD) and influence the development of the disease. Most of the acupuncture points selected for GAD are based on the principles of local acupuncture points and acupuncture points following the distant channels of the meridians, regarding Baihui (DU 20), Fengchi (GB 20), and Yintang (GV 29) as the main acupuncture points, and the acupuncture points selected for the regulation of GF are Zhongwan (CV 12), Tianshu (ST 25), and Guanyuan (RN 4) and Zusanli (ST 36). Recently, many studies have been conducted on the mechanism of action of acupuncture in the treatment of GAD from the perspective of GF, but few have investigated the theoretical of acupuncture points used to prevent and treat GAD. This paper discusses the theoretical basis of acupuncture to regulate the "microbiota-gut-brain axis" (MGBA) for the prevention and treatment of GAD, and proposes the method of "regulating the internal organs and calming the mind and relieving anxiety" through analyzing the researches on the regulation of GF and GAD.
3.Cucumber downy mildew and the mechanisms of host resistance: a review.
Shicheng XU ; Hebing WANG ; Junjie FENG ; Huafeng XIANG ; Mengdan WU ; Zhimin WANG ; Dayong WEI ; Hongcheng ZHANG ; Qinglin TANG
Chinese Journal of Biotechnology 2022;38(5):1724-1737
The cultivation and production of cucumber are seriously affected by downy mildew caused by Pseudoperonospora cubensis. Downy mildew damages leaves, stems and inflorescences, and then reduces the yield and quality of cucumber. This review summarized the research advances in cucumber downy mildew, including pathogen detection and defense pathways, regulatory factors, mining of pathogens-resistant candidate genes, proteomic and genomic analysis, and development of QTL remarks. This review may facilitate clarifying the resistance mechanisms of cucumber to downy mildew.
Cucumis sativus/genetics*
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Oomycetes/genetics*
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Peronospora
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Plant Diseases/genetics*
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Proteomics
4.Influence of the antithrombotic pressure pump on the intracranial pressure of the severe traumatic brain injury patients
Yuping LU ; Shanshan HONG ; Jianying WANG ; Xueyan WU ; Liping HUANG ; Yanhong FENG ; Yanbo SONG ; Yaqiong GAO ; Juan XU ; Mengdan SI ; Wei WU ; Kaixuan YAN
Chinese Journal of Modern Nursing 2016;22(12):1714-1717
Objective To evaluate effect of antithrombotic pressure pump on the intracranial pressure (ICP) of the severe traumatic brain injury(STBI) patients who were performed the surgery.Methods A total of 120 consecutive STBI patients after the surgery , who were admitted at Neurological Intensive Care Units (NICU) from April 2013 to September 2014, were randomly divided into (research group and control group ). Each group had 60 patients .In the 6 days observation , research group received the treatment of antithrombotic pressure pump among the first 3 days after the surgery , and the treatment was stopped among the last 3 days. Control group received the opposite treatment .ICP was continuously monitored and all the data ( mean ICP, times of ICP ≥20 mmHg, the highest ICP per day ) were performed statistical analysis .Results Mean ICP,times of ICP≥20 mmHg and the highest ICP per day in two groups decreased significantly after the surgery ( P<0.05).The difference of Mean ICP, times of ICP ≥20 mmHg and the highest ICP per day between the two groups were not significant .No patient got the deep vein thrombosis ( DVT ) .Conclusions Antithrombotic pressure pump could efficiently prevent deep vein thrombosis , which is a safe treatment for STBI patients and has no influence on the ICP .

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