1.DUSP26 inhibits proliferation, migration, and invasion of lung adenocarcinoma A549 cells by suppressing the TGF-β1/SMAD2/3 signaling pathway
LUO Fengheng ; WU Min ; ZHOU Shan ; XIAO Yanan ; ZHAN Zhiqiang
Chinese Journal of Cancer Biotherapy 2025;32(7):738-745
[摘 要] 目的:探究双特异性磷酸酶26(DUSP26)在肺腺癌(LUAD)A549细胞增殖、迁移和侵袭中的作用及其分子机制。方法:检索肿瘤数据库GEPIA2网站DUSP26表达数据,分析DUSP26在LUAD患者和正常人肺组织中的表达差异。收集2022年10月至2023年10月期间萍乡市人民医院手术切除的12例LUAD组织和癌旁组织标本,通过免疫组织化学(IHC)和WB法检测DUSP26在LUAD组织和癌旁组织之间的表达差异;通过WB法检测DUSP26在4种LUAD细胞(A549、SK-LU-1、Calu-3、H1299)和2种正常支气管上皮细胞(BEAS-2B、HBEC)中的表达差异。利用慢病毒转染细胞的方法构建稳定过表达DUSP26(DUSP26-OE)及阴性对照(DUSP26-OENC)的A549细胞,通过克隆形成、划痕愈合实验、Transwell实验分别检测DUSP26过表达对细胞增殖、迁移及侵袭能力的影响,WB法检测各组细胞中TGF-β1/SMAD2/3通路、EMT相关蛋白的表达水平,细胞免疫荧光法检测细胞中Ki-67、cyclin D1表达水平。加入TGF-β1重组蛋白进行回复实验。构建A549细胞裸鼠荷瘤模型,观察DUSP26过表达对移植瘤体内生长的影响,WB法检测移植瘤组织中TGF-β1/SMAD2/3通路、EMT相关蛋白表达水平,免疫荧光染色法检测移植瘤组织中Ki-67、cyclin D1表达水平。结果:DUSP26在LUAD组织和细胞中均呈低表达(P < 0.05或P < 0.01或P < 0.001或P < 0.000 1)。与DUSP26-OENC组相比,DUSP26-OE组A549细胞的增殖、迁移和侵袭能力均显著降低(P < 0.01或P < 0.001),TGF-β1、p-SMAD2/3、vimentin、N-cadherin、snail、Ki-67、cyclin D1表达均降低(P < 0.01或P < 0.001或P < 0.000 1),E-cadherin表达升高(P < 0.000 1)。加入5 ng/mL TGF-β1重组蛋白后,可部分逆转在体外实验中由DUSP26过表达导致的结果。成功构建裸鼠A549细胞荷瘤模型,DUSP26-OE组裸鼠移植瘤生长速度缓慢,体积和质量均减小(均P < 0.001),移植瘤组织中TGF-β1、p-SMAD2/3、vimentin、N-cadherin、snail、Ki-67、cyclin D1表达均降低(P < 0.01或P < 0.001),E-cadherin表达升高(P < 0.000 1)。结论:DUSP26在LUAD组织和细胞中均呈低表达状态,上调DUSP26的表达水平能够通过抑制TGF-β1/SMAD2/3信号通路抑制A549细胞的增殖、迁移和侵袭。
2.Vonoprazan-based quadruple therapy is non-inferior to esomeprazole-based quadruple therapy for Helicobacter pylori eradication: A multicenter, double-blind, randomized, phase 3 study.
Zhiqiang SONG ; Qin DU ; Guoxin ZHANG ; Zhenyu ZHANG ; Fei LIU ; Nonghua LU ; Liqun GU ; Shingo KURODA ; Liya ZHOU
Chinese Medical Journal 2025;138(22):2938-2946
BACKGROUND:
Owing to the high prevalence of antibiotic resistance in Helicobacter pylori ( H. pylori ) in China, bismuth-containing quadruple therapies have been recommended for H. pylori eradication. This study compared the efficacy and safety of quadruple regimens containing vonoprazan vs . esomeprazole for H. pylori eradication in a patient population in China.
METHODS:
This was a phase 3, multicenter, randomized, double-blind study. Patients with confirmed H. pylori infection were randomized 1:1 to receive quadruple therapy for 14 days: amoxicillin 1000 mg and clarithromycin 500 mg after meals, bismuth potassium citrate 600 mg before meals, plus either vonoprazan 20 mg or esomeprazole 20 mg before meals, all twice daily. The primary outcome was the eradication rate of H. pylori , evaluated using a 13 C urea breath test at 4 weeks after treatment. The non-inferiority margin was at 10%.
RESULTS:
The study included 510 patients, 506 of whom completed the follow-up assessment. The primary analysis revealed eradication rates of 86.8% (210/242) and 86.7% (208/240) for vonoprazan and esomeprazole therapy, respectively (treatment difference: 0.1%; 95% confidence interval [CI]: -5.95, 6.17; non-inferiority P = 0.0009). Per-protocol analysis showed eradication rates of 87.4% for vonoprazan and 86.3% for esomeprazole (treatment difference: 1.2%; 95% CI: -5.03, 7.36; non-inferiority P = 0.0004). Vonoprazan and esomeprazole were well tolerated, with similar safety profiles.
CONCLUSION:
Vonoprazan was found to be well-tolerated and non-inferior to esomeprazole for eradicating H. pylori in patients from China.
TRIAL REGISTRATION
ClinicalTrials.gov , NCT04198363.
Humans
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Esomeprazole/therapeutic use*
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Double-Blind Method
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Helicobacter Infections/drug therapy*
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Male
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Female
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Middle Aged
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Helicobacter pylori/pathogenicity*
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Pyrroles/therapeutic use*
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Sulfonamides/therapeutic use*
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Adult
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Clarithromycin/therapeutic use*
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Amoxicillin/therapeutic use*
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Aged
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Anti-Bacterial Agents/therapeutic use*
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Pyrrolidines/therapeutic use*
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Drug Therapy, Combination
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Proton Pump Inhibitors/therapeutic use*
3.A critical role for Phocaeicola vulgatus in negatively impacting metformin response in diabetes.
Manyun CHEN ; Yilei PENG ; Yuhui HU ; Zhiqiang KANG ; Ting CHEN ; Yulong ZHANG ; Xiaoping CHEN ; Qing LI ; Zuyi YUAN ; Yue WU ; Heng XU ; Gan ZHOU ; Tao LIU ; Honghao ZHOU ; Chunsu YUAN ; Weihua HUANG ; Wei ZHANG
Acta Pharmaceutica Sinica B 2025;15(5):2511-2528
Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.
4.Metabolic engineering of Escherichia coli for the biosynthesis of O-acetyl-L-homoserine.
Lianggang HUANG ; Feng GAO ; Nuoran XU ; Junping ZHOU ; Kun NIU ; Bo ZHANG ; Zhiqiang LIU ; Yuguo ZHENG
Chinese Journal of Biotechnology 2025;41(1):256-270
O-acetyl-L-homoserine (OAH) is a promising platform compound for the production of L-methionine and other valuable compounds, while its low yield and low conversion rate limit the industrial application. To solve these problems, we constructed a strain for high OAH production with the previously constructed L-homoserine producer Escherichia coli HS33 as the chassis by systematic metabolic engineering. Firstly, PEP accumulation, pyruvate utilization, and OAH synthesis pathway (overexpressing aspB, aspA, and thrAC1034T) were enhanced to obtain an initial strain accumulating 13.37 g/L OAH. Subsequently, the co-factor synthesis genes were integrated to supply reducing power and energy, which increased the yield to 15.79 g/L. The OAH yield of the engineered strain OAH28 was further increased to 17.49 g/L by strengthening the acetic acid reuse pathway, improving the supply of acetyl-CoA, and regulating the expression of MetX from different sources. Finally, in a 5 L fermenter, OAH28 achieved an OAH titer of 47.12 g/L, with a glucose conversion rate of 32% and productivity of 0.59 g/(L·h). The results lay a foundation for increasing the OAH production by metabolic engineering and give insights into the industrial production of OAH.
Metabolic Engineering/methods*
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Escherichia coli/genetics*
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Homoserine/biosynthesis*
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Fermentation
5.Preparation of multi-layer compound microcapsules and their application in self-healing of concrete cracks.
Jianmiao XU ; Yuanyuan ZHOU ; Feng CHENG ; Zhiqiang LIU
Chinese Journal of Biotechnology 2025;41(1):448-460
Concrete is widely used in building construction, civil engineering, roads, bridges, etc., but concrete cracking remains a major issue in the engineering industry. To develop an effective and feasible concrete repair technology, this study combined microbial and microencapsulation technologies to prepare a multi-layer compound microcapsule using the piercing method. The formulation and drying method of microcapsules were optimized by taking their embedding rate and mechanical properties as evaluation criteria. The calcium transcrystallization process of microcapsules and the crystal form of products were characterized and compared with the calcium transcrystallization process in free cells. Finally, the effects of microcapsule incorporation on mechanical properties, impermeability, and self-healing performance of concrete specimens were then tested. The results showed that the air-dried multi-layer compound microcapsules, formulated with 1.0% wet cells of Bacillus cereus, 1.5% calcium chloride, 3.0% sodium alginate, 5.0% nutrients, 6.0% glycerol, 0.6% chitosan, and 2.0% urea, achieved an embedding rate of 95.3%, a rupture force of 60.0 N and a hardness of 150.8 N. These microcapsules can transform from a solid state to a flowing colloidal state when the microorganisms inside undergo a calcium formation reaction. Both the microcapsules and free cells produced stable calcite crystal forms of calcium carbonate through the calcium conversion reaction, with the microcapsules producing more uniform-sized particles, which are more conducive to accumulation in cracks, thereby enhancing the stability of repair. When microcapsules were incorporated into the concrete specimen at a content of 0.45%, the flexural strength of the specimen increased by 17.3%, and the compressive strength increased by 12.3%. In the water impermeability test, specimens with microcapsules demonstrated better impermeability compensation for the cement concrete than those with free cells. The self-healing effect of cracks proved that multi-layer compound microcapsules could completely repair cracks up to 0.7 mm wide, and a repair rate of 95% for 0.8 mm wide cracks. In this study, a multi-layer compound microcapsule was developed to protect microorganisms in concrete and provide nutrients required for their growth, which provided a new idea for microbial induced calcium carbonate precipitation in concrete crack repair.
Construction Materials
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Capsules/chemistry*
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Bacillus cereus/metabolism*
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Alginates/chemistry*
6.Exploration and practice of teaching reform in Synthetic Biology.
Bo ZHANG ; Lianggang HUANG ; Aiping PANG ; Zheyan WU ; Junping ZHOU ; Xue CAI ; Lijuan WANG ; Kun NIU ; Liqun JIN ; Zhiqiang LIU ; Yuguo ZHENG
Chinese Journal of Biotechnology 2025;41(8):3311-3317
Synthetic biology is a crucial tool for the development of the bio-industry and bio-economy, representing a significant aspect of new quality productive forces. As a core course for graduate students in bioengineering, Synthetic Biology plays a vital role in ensuring the supply of essential talents for the development of the bio-industry in the new era. To better serve regional economic development and provide high-level talents for China's progress in the bio-industry, we analyzed typical issues encountered in the past teaching activities, set up a multi-disciplinary teaching team, optimized the course contents, adjusted the teaching mode, and mobilized students' learning interest. With the application of scientific research project as the starting point, we guided students to think and discuss deeply through the simulation of application writing and project defense, which improved students' critical thinking and innovative thinking. With industrialization as a focus, we explored a new training model combining production, education, and research through the joint practice base of the university and enterprises introduced typical cases of biomanufacturing to encourage students to engage in scientific research. The teaching reform significantly enhances the comprehensive abilities and national sentiments of graduate students. This paper hopes to serve as a reference for colleagues engaged in teaching in this field.
Synthetic Biology/education*
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Teaching
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China
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Humans
7.A Multicenter, Randomized, Double-blind, and Placebo-parallel Controlled Trial of Tibetan Medicine Ruyi Zhenbaowan in Treatment of Knee Osteoarthritis
Chunquan SUN ; Yanming XIE ; Jinghua GAO ; Weiheng CHEN ; Lianxin WANG ; Shangquan WANG ; Xiangdong TIAN ; Zujian XU ; Yuxin ZHENG ; Mingwang ZHOU ; Chungen LI ; Zhanwang XU ; Jiayi GUO ; Shuangqing DU ; Qigang CHEN ; Quan JI ; Zhiqiang BAI ; Jing XIAO ; Wanli QI ; Weiyi YANG ; Jingxiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):57-67
ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan(RYZBW)in the treatment of initial and early knee osteoarthritis (KOA) through a prospective multicenter,randomized,double-blind,and placebo-parallel controlled trial. MethodFrom October 13th, 2021 to December 25th, 2021, 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital, Chinese Academy of Chinese Medical Sciences, and they were randomly divided into observation group and control group, with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education, and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks, and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score (WOMAC score), and the secondary outcome measures were the response rate of visual scale (VAS) pain score, WOMAC sub item scores (joint pain, joint stiffness, and joint function), quality of life (SF-12) score, and traditional Chinese medicine (TCM) syndrome score. Result(1) Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW, and the difference was statistically significant (P<0.05). There was no significant difference between the two groups in improving VAS score response rate, WOMAC function score, WOMAC stiffness score, SF12-PCS (quality of life-physical health) score, SF12-MCS (quality of life-mental health) score, and TCM syndrome score. (2) Subgroup analysis. ① In terms of VAS score response rate, the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of (4, 5], and the difference was statistically significant (P<0.05). ② In terms of TCM syndrome score, for subjects aged [56, 60] and [61, 65], the decrease in total TCM syndrome score in the observation group was better than that in the control group, and the difference was statistically significant (P<0.05). ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score, VAS score response rate, WOMAC pain score, WOMAC function score, and TCM syndrome score for patients with initial and early KOA, which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.
8.Effect of Jiuxin Pill (救心丸)on Exercise Tolerance and Quality of Life in Patients of Stable Angina Pectoris:A Randomized,Double-Blind,Placebo-Controlled,Multi-Center Clinical Trial
Xianliang WANG ; Mingjun ZHU ; Daimei NI ; Jianguang WU ; Yitao XUE ; Chenglong WANG ; Xiaohua DAI ; Qian LIN ; Jun LI ; Zhiqiang ZHAO ; Shuai WANG ; Yingfei BI ; Tongzuo LIU ; Zhou ZHOU ; Jingyuan MAO
Journal of Traditional Chinese Medicine 2024;65(24):2549-2557
ObjectiveTo evaluate the effect and safety of Jiuxin Pill (救心丸) on exercise tolerance and quality of life in patients with stable angina pectoris (SAP). MethodsA randomised, double-blind, placebo-controlled, multicentre study design was used to enroll 170 patients of SAP from nine centres, which were divided into 85 patients each in the trial group and control group with 1∶1 ratio. Both groups maintained the original western medicine treatment plan, and added Jiuxin Pill or placebo respectively, 2 pills (0.05 g) each time twicely for 28 days. The main outcomes were total exercise time (TED) in the exercise treadmill test and Seattle Angina Questionnaire (SAQ) scores including physical limitation (PL), angina stability (AS), angina frequency (AF), treatment satisfaction (TS), and disease perception (DP). The secondary outcomes were exercise treadmill test indicators including heart rate recovery in 1 min (HRR1), metabolic equivalents (METs), maximum magnitude of ST-segment depression, and the Borg rating of perceived exertion scale, the average number of angina attacks per week, withdrawal and reduction rate of nitroglycerin, traditional Chinese medicine syndrome scores, incidence of major adverse cardiovascular events. Safety indicators were evaluated and the occurrence of adverse events during the trial was recorded. Data was collected before treatment, day 28±2 in treatment period, and follow-up at day 56 which is 28±2 days after treatment period finished. ResultsEighty-four and eighty-five patients respectively from trial group and control group were included to the full analysis set (FAS) and safety analysis set (SS). Compared with the group before treatment and with the control group after treatment, the trial group had higher TED, HRR1, and METs, and lower maximum magnitude of ST-segment depression and Borg rating of perceived exertion scores after treatment (P<0.01). Compared with the group before treatment and with the control group after treatment and at follow-up, the total SAQ score and scores of AS, AF, TS and DP of the trial group after treatment and at follow-up elevated, while the average number of angina attacks per week and traditional Chinese medicine syndrome scores reduced (P<0.01). There was no statistically significant difference in the withdrawal and reduction rate of nitroglycerin between groups (P>0.05). Major adverse cardiovascular events occurred in 1 case (1/84, 1.19%) in the trial group and 1 case (1/85, 1.18%) in the control group, and the difference between groups was not statistically significant (P>0.05). A total of 3 cases of adverse events occurred in the trial group (3/84, 3.57%), and a total of 6 cases of adverse events occurred in the control group (6/85, 7.06%), and there was no statistically significant difference in the incidence of adverse events between groups (P>0.05). ConclusionIn the treatment of SAP, Jiuxin Pill combined with conventional western medicine can further enhance exercise tolerance, improve quality of life, and demonstrate great safety.
9.Esketamine Improves Working Memory Impairment in Neuropathic Mice Through Hippocampal BDNF-TrkB Pathway
Yubin JIANG ; Xingming WANG ; Yue ZHANG ; Zhiqiang ZHOU ; Jianjun YANG
Medical Journal of Peking Union Medical College Hospital 2024;15(2):328-334
10.Changes in corneal epithelial thickness and optical density and their correlation after smart pulse technology-assisted transepithelial photorefractive keratectomy
Shiyang NIU ; Hua YANG ; Yan LI ; Zhiqiang DAI ; Xinmin LI ; Yulan ZHOU ; Ouyang ZHANG ; Baojun WANG
International Eye Science 2024;24(8):1308-1313
AIM: To evaluate the changes in corneal epithelial thickness(CET)and corneal optical density(CD)after smart pulse technology(SPT)-assisted transepithelial photorefractive keratectomy(TPRK)and analyze their correlation.METHODS: The prospective study included 60 patients(120 eyes)with myopia and myopic astigmatism who underwent SPT-TPRK in the ophthalmology department at the First Affiliated Hospital of Xinxiang Medical University between February and August 2023. Changes in CET and CD were evaluated preoperatively and at 1 wk, 1 and 3 mo postoperatively.RESULTS: A total of 14 cases(28 eyes)were lost to follow-up, and 3 patients(6 eyes)with postoperative haze were excluded from this study, resulting in a final inclusion of 43 patients(86 eyes). At 1 wk after SPT-TPRK, CET had statistically significantly thickened compared to preoperative levels(P<0.05), particularly in the CET at 0-2 mm central corneal area(P<0.05). At 1 mo after SPT-TPRK, the CET at 0-2 mm area had statistically significantly decreased(P<0.05). At 3 mo after SPT-TPRK, the CET at 0-2 mm had essentially reached preoperative levels. Postoperative CD values increased, with a positive correlation between CET in the 0-2 mm area and CD in the whole 0-2 mm area(r=0.256, P<0.05), and a positive correlation between CET in the 2-5 mm area and CD in the anterior 2-6 mm area(r=0.319, P<0.05).CONCLUSION: Corneal epithelial remodeling takes 3 mo in areas within 2 mm of the central cornea; areas with thinner CET have faster postoperative corneal epithelial remodeling and greater thickening in the early postoperative period; CD increases in the early postoperative period compared to the preoperative value, and in some areas, there is a positive correlation between CET and CD value.

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