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MiR-592 Attenuates Tamoxifen Resistance in Breast Cancer Through PIK3CA-Mediated PI3K/AKT/mTOR Signaling Pathway

APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY 2025年第3期197卷 2051-2065页

作者： Jin, Conghui Gao, Xiangxiang Ni, Jingyi zhang, baochun Wang, Zhenxin Soochow Univ Affiliated Hosp 1 Dept Med Oncol Suzhou 215006 Jiangsu Peoples R China Nantong Univ Affiliated Tumor Hosp Dept Med Oncol Nantong 226361 Jiangsu Peoples R China

Tamoxifen (TAM) is vital in breast cancer (BC) treatment, yet its resistance significantly impairs its efficacy. While miR-592 is known for its suppressive role in BC, its effect on chemotherapy resistance remains unclear. In this study, we observed a significant reduction in miR-592 levels in TAM-resistant BC tissues and cell lines. Low miR-592 expression was significantly associated with advanced TNM stage, lymph node metastasis, and poorer patient survival. Dual-luciferase assay confirmed miR-592 binding to the predicted gene PIK3CA. Increasing miR-592 levels decreased the IC50 of TAM, inhibited cell viability, migration, and invasion, and enhanced apoptosis in vitro, which was mimicked by PIK3CA knockdown and reversed by PIK3CA overexpression. Moreover, miR-592 upregulation suppressed tumor growth and improved TAM responsiveness in vivo. Molecularly, both si-PIK3CA and miR-592 mimics decreased the expression ratios of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR, while increasing cleaved caspase-3 and E-cadherin expression in MCF-7/TAM cells. PIK3CA overexpression partially reversed these reductions. In conclusion, our study demonstrates that miR-592 attenuates TAM resistance by inhibiting the PIK3CA-driven PI3K/AKT/mTOR signaling pathway, representing a promising strategy to address chemoresistance in BC.

关键词： Breast cancer Tamoxifen resistance MiR-592 PIK3CA PI3K/AKT/mTOR signaling

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Cloning and characterization of a novel recombinant multifunctional glycoside hydrolase β-D-xylosidase/α-L-arabinopyranosidase/β-glucosidase from Bifidobacterium adolescentis and its application on the biotransformation of ginsenoside Rb3

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BIOCATALYSIS AND BIOTRANSFORMATION 2025年第1期43卷 97-108页

作者： Zhao, Jun zhang, baochun Shen, Yuzhu Zhou, Jianing Li, Yiming Hu, Yanbo Changchun Univ Sch Food Sci & Engn Changchun 130024 Peoples R China

beta-D-xylosidase, an important glycoside hydrolase, hydrolyzes xylo-oligosaccharides to yield xylose and biotransforms specific saponins by cleaving beta-xylose at the non-reducing end. It is extensively employed in renewable resources, including fuels, food, and pharmaceuticals, as a xylanolytic enzyme. In this study, a 1197 bp beta-xylosidase gene (BaXyl5B) derived from Bifidobacterium adolescentis was cloned and expressed in E. coli BL21. Following purification, the recombinant beta-xylosidase exhibited a distinct band on SDS-PAGE;its molecular weight was determined to be 46.4 kDa. The optimal activity of BaXyl5B was observed at a pH of 6.0 and a temperature of 30 degrees C. Purified BaXyl5B demonstrated multifunctional activities involving p-nitrophenyl-beta-D-xylopyranoside (pNP beta Xyl), p-nitrophenyl-alpha-L-arabinopyranoside (pNP alpha Arap), and p-nitrophenyl-beta-D-glucopyranoside (pNP beta Glc). A significant finding of this study was that BaXyl5B exhibited high selectivity towards ginsenoside Rb3, which could hydrolyze xylose at the C-20 position of Rb3 to yield Rd and F2. Overall, this research explored a novel beta-xylosidase, BaXyl5B, that could serve as a valuable biocatalyst for converting ginsenosides and synthesizing active glycosides and aglycones, making it a promising enzyme for further exploration and utilization.

关键词： Bifidobacterium adolescentis beta-xylosidase substrate selectivity ginsenoside Rb3 ginsenoside F2

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NIR-II DNA Nanodevice for Spatiotemporal MicroRNAs Imaging Based on "and" Logic-Gate Strategy

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ADVANCED FUNCTIONAL MATERIALS 2025年

作者： Li, Lei zhang, baochun Wang, Yifan Han, Hui Chen, Kai Li, Meixing Fan, Quli zhang, Hui Shen, Qingming Nanjing Univ Posts & Telecommun Inst Adv Mat IAM State Key Lab Flexible Elect LoFE Nanjing 210023 Peoples R China Nanjing Univ Posts & Telecommun Inst Adv Mat IAM Jiangsu Key Lab Biosensors Nanjing 210023 Peoples R China Nanjing Normal Univ Sch Chem & Mat Sci Jiangsu Key Lab New Power Batteries Nanjing 210023 Peoples R China

The precise detection of multiple microRNAs (miRNAs) is of great significance to the classification of various cell subtypes. However, miRNA detection is hindered by signal leakage, false-positive signals and low expression of miRNAs. Herein, a DNA nanodevice in the second near infrared region (NIR-II, 1000-1700 nm) (DND-II) is developed for dual miRNAs bioimaging based on "AND" logic-gate signal amplification strategy. The spatiotemporally controlled logic-gate-based DND-II is fabricated by thermosensitive liposomes integrated with the second near-infrared DNA probes. In particular, the "always-on" photoacoustic signal of DNA probes provided an additional imaging tool to monitor the distribution of DND-II in vivo. When both miRNAs are present, the DNA probes generated a "turn on" fluorescent signal through DNA logical analysis and molecular computation, further triggering an entropy-driven dual-cycle fluorescence signal amplification. The spatiotemporal DND-II provides a powerful platform for early diagnosis and photothermal ablation of different subtypes of tumor cells.

关键词： DNA nanodevice logic gate circuit microRNAs NIR-II fluorescence imaging spatiotemporal activation

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Efficacy and safety of KN026 and docetaxel for HER2-positive breast cancer: a phase II clinical trial

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CANCER COMMUNICATIONS 2025年第4期45卷 476-485页

作者： Ma, Jianli Wang, Jingxuan Xu, Ting Ouyang, Quchang Wang, Xiaojia Wang, Jingfen Gan, Lu Ouyang, Zhong Lin, Daren Sun, Tao Shan, Changping Yao, Herui zhang, baochun Li, Zhengguang Zhuang, Zhixiang Lu, Ying Yang, Hongwei Huang, Jian Yang, Xingwang Sun, Hongmei zhang, Qingyuan Harbin Med Univ Canc Hosp Dept Radiotherapy Harbin Heilongjiang Peoples R China Harbin Med Univ Canc Hosp Dept Med Oncol Harbin Heilongjiang Peoples R China Jiangsu Alphamab Biopharmaceut Co Ltd Dept President Suzhou Jiangsu Peoples R China Hunan Canc Hosp Dept Breast Med Changsha Hunan Peoples R China Zhejiang Canc Hosp Dept Breast Med Oncol Hangzhou Zhejiang Peoples R China Linyi Canc Hosp Dept Med Oncol Linyi Shandong Peoples R China First Affiliated Hosp Chongqing Med Univ Dept Gastroenterol Chongqing 400016 Peoples R China First Affiliated Hosp Xiamen Univ Dept Pathol Xiamen 361003 Fujian Peoples R China Jiangmen Cent Hosp Dept Oncol Jiangmen Guangdong Peoples R China Liaoning Canc Hosp & Inst Dept Breast Oncol Shenyang 110042 Liaoning Peoples R China Jining Med Univ Dept Oncol Affiliated Hosp Jining Jining Peoples R China Sun Yat Sen Univ Sun Yat Sen Mem Hosp Breast Tumor Ctr Guangzhou Guangdong Peoples R China Nantong Liangchun Hosp Tradit Chinese Med Dept Oncol Nantong Jiangsu Peoples R China Chengdu Seventh Peoples Hosp Dept Cardiol Chengdu Sichuan Peoples R China Soochow Univ Dept Oncol Affiliated Hosp 2 Suzhou Jiangsu Peoples R China Liuzhou Workers Hosp Dept Oncol Liuzhou Guangxi Peoples R China Suining Cent Hosp Dept Breast & Thyroid Surg Suining Sichuan Peoples R China Zhejiang Univ Sch Med Affiliated Hosp 2 Dept Breast Surg Hangzhou Zhejiang Peoples R China Zibo Municipal Hosp Dept Gen Surg Zibo Shandong Peoples R China Jiamusi Canc & TB Hosp Jiamusi Heilongjiang Peoples R China

BackgroundThe standard first-line treatment for human epidermal growth factor receptor 2 (HER2)-positive recurrent/metastatic breast cancer currently includes pertuzumab plus trastuzumab and docetaxel. This study aimed to evaluate the effectiveness of KN026, an anti-HER2 bispecific antibody, plus docetaxel in first-line treatment of HER2-positive recurrent/metastatic breast *** open-label, single-arm, phase II study enrolled patients with HER2-positive recurrent/metastatic breast cancer in 19 centers across China from December 30, 2019 to May 27, 2021. Patients were administered KN026 (30 mg/kg) plus docetaxel (75 mg/m2) in 21-day cycles. Primary endpoints included the objective response rate (ORR) and duration of response (DOR). In addition, overall survival (OS), progression-free survival (PFS), clinical benefit rate (CBR) and safety profile were *** total of 57 patients were included. In the efficacy analysis set of 55 patients, the ORR was 76.4% (95% confidence interval [CI], 63.0%-86.8%), and the CBR was 85.5% (95% CI, 73.3%-93.5%). The median DOR was not reached (95% CI, 20.7 months-not reached). In the safety set of 57 patients, the median PFS was 27.7 months (95% CI, 18.0 months-not reached). The median OS was not reached, with OS rates at 12, 24 and 30 months of 93.0%, 84.1% and 78.5%, respectively. Grade >= 3 treatment-emergent adverse events (AEs) were detected in 36 (63.2%) patients. No deaths were attributed to KN026 or ***026 plus docetaxel showed promising efficacy and a manageable safety profile in first-line treatment of HER2-positive recurrent/metastatic breast cancer.

关键词： Breast Neoplasms Antineoplastic Agents anti-HER-2 Bispecific Antibody Phase II Clinical Trial Docetaxel

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Genetic drivers of NF-κB deregulation in diffuse large B-cell lymphoma

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SEMINARS IN CANCER BIOLOGY 2016年第0期39卷 26-31页

作者： Pasqualucci, Laura zhang, baochun Columbia Univ Inst Canc Genet Dept Pathol & Cell Biol Herbert Irving Comprehens Canc Ctr New York NY 10032 USA Harvard Med Sch Dana Farber Canc Inst Dept Med Oncol Boston MA 02215 USA

Diffuse large B cell lymphoma (DLBCL) is the most common form of B cell non-Hodgkin lymphoma worldwide and comprises a heterogeneous group of malignancies that originate from the malignant transformation of germinal center (GC) B cells. Over the past decade, significant improvement has been achieved in our understanding of the molecular pathogenesis underlying this disease, thanks in part to the implementation of powerful genomic technologies allowing genome-wide structural and functional analyses. These studies revealed the presence of multiple oncogenic alterations dysregulating signal transduction pathways that are normally required for the normal biology of the cells from which these tumors are derived. Among the pathways identified as recurrent targets of genetic lesions in DLBCL, NF-kappa B has emerged as a central player in the development and maintenance of this disease, particularly in the less curable, activated B cell (ABC)-like subtype. These lesions reveal vulnerabilities of the lymphoma cells that can be exploited for the design of more rationale therapeutic approaches. The purpose of this review is to summarize recent progresses in understanding the role of NF-kappa B deregulation in the pathogenesis of DLBCL, with emphasis on the genetic basis underlying its aberrant activation, in relationship to the normal biology of B lymphocytes, and the modelling of these lesions in the mouse. (C) 2016 Published by Elsevier Ltd.

关键词： DLBCL Germinal center NF-kappa B Genetic lesions

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Magnetic properties of high-road-side pine tree leaves in Beijing and their environ-mental significance

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Chinese Science Bulletin 2006年第24期51卷 3041-3052页

作者： zhang Chunxia HUANG baochun LI Zhenyu LIU He Paleomagnetism and Geochronology Laboratory (SKL-LE) Institute of Geology and Geophysics Chinese Academy of Sciences Beijing 100029 China

This is a report on magnetic properties of highroad-side tree (Pinus pumila Regel) leaves collected along an expressway linking Beijing City and the Capital International Airport and further focus on their environmental contributions. A series of rock magnetic experiments show that the primary mag-netic mineral of leaf samples was identified to be magnetite,in the pseudo-single domain (PSD) grain size range 0.2―5.0 μm. On the other hand,magnet-ite concentration and grain size in leaves are ascer-tained to decrease with increasing of sampling dis-tance to highroad asphalt surface,suggesting that high magnetic response to traffic pollution is localized within a distance of some two meters away from highroad asphalt surface. Although magnetic suscep-tibility is ordinarily regarded as a simple,rapid and low-cost method for monitoring traffic pollution,saturation isothermal remanent magnetization (SIRM) can be treated as a valid proxy for monitoring air par-ticulate matter (PM) when samples are magnetically weak. It is believed that a synthetic rock magnetic study is an effective method for determining concen-tration and grain size of ferromagnets in the atmos-pheric PM,and then it should be a rapid and feasible technique for monitoring atmospheric pollution.

关键词：公路行道树路侧树木松树树叶交通污染空气污染磁学性质

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Cyclic AMP Inhibits IL-1β Plus IFNγ-Induced NF-κB Translocation in Hepatocytes by a PKA Independent Mechanism

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JOURNAL OF SURGICAL RESEARCH 2010年第1期159卷 565-571页

作者： Hong, Guiying zhang, baochun Harbrecht, Brian G. Univ Louisville Hlth Sci Ctr Dept Surg Louisville KY 40202 USA Univ Pittsburgh Med Ctr Dept Surg Pittsburgh PA USA

We previously showed that cAMP inhibits IL-1 beta plus IFN gamma-induced NF-kappa B binding in primary hepatocytes but the signaling mechanisms responsible for this effect are not understood. In this study, the role of PICA in mediating the effect of cAMP on NF-kappa B was investigated. Immunofluorescent staining showed that cAMP inhibited IL-1 beta plus IFN gamma-induced translocation of NF-kappa B into the nucleus. Western blot analysis showed that the IL-1 beta plus IFN gamma-induced phosphorylation and degradation of I kappa Ba were markedly inhibited by cAMP. Immunocomplex assay involving GST-IKK revealed that cAMP inhibited IL-1 beta plus IFN gamma-induced IKK activity. The PICA inhibitors had no effect on the inhibition of NF-kappa B binding by cAMP and did not change the p65 and IKB level induced by cAMP. Overexpression of PICA increased IL-1 plus IFN gamma-induced NF-kappa B binding. These results suggest that PICA is not essential for the inhibitory effect of cAMP on NF-kappa B binding activity in hepatocytes. We demonstrated that cAMP inhibits IL-1 beta plus IFN gamma-induced NF-kappa B binding due to its blockade of the upstream signal(s) leading to IKB phosphorylation and degradation, and is mediated by PICA-independent signaling pathways. (C) 2010 Elsevier Inc. All rights reserved.

关键词： cyclic AMP IKK NF-kappa B hepatocyte PKA

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Akt-mediated signaling is induced by cytokines and cyclic adenosine monophosphate and suppresses hepatocyte inducible nitric oxide synthase expression independent of MAPK P44/42

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BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH 2011年第1期1813卷 73-79页

作者： zhang, baochun Li, Suping Harbrecht, Brian G. Univ Louisville Dept Surg Louisville KY 40292 USA

Cyclic AMP inhibits the expression of nitric oxide synthase (Harbrecht et al., 1995 [1]) in hepatocytes but the mechanism for this effect is incompletely understood. Cyclic AMP can activate several intracellular signaling pathways in hepatocytes including Protein Kinase A (PKA), cAMP regulated guanine nucleotide exchange factors (AMP-GEFs), and calcium-mediated Protein Kinases. There is considerable overlap and cross-talk between many of these signaling pathways, however, and how these cascades regulate hepatocyte iNOS is not known. We hypothesized that Akt mediates the effect of cAMP on hepatocyte iNOS expression. Hepatocytes cultured with cytokines and dbcAMP increased Akt phosphorylation up to 2 h of culture. Akt phosphorylation was inhibited by the PI3K inhibitor LY294002 (10 mu M), farnyltranferase inhibitor FTI-276, or transfection with a dominant negative Akt. The cyclic AMP-induced suppression of cytokine-stimulated iNOS was partially reversed by LY294002 and FTI-276. LY294002 also increased NF kappa B nucleus translocation by Western blot analysis in nuclear extracts. Cyclic AMP increased phosphorylation of Raf1 at serine 259 which was blocked by LY294002 and associated with decreased MAPK P44/42 phosphorylation. However, inhibition of MAPK P44/42 signaling with PD98059 failed to suppress cytokine-induced hepatocyte iNOS expression and did not enhance the inhibitory effect of dbcAMP on iNOS production. A constitutively active MAPK P44/42 plasmid had no effect on cytokine-stimulated NO production. These data demonstrate that dbcAMP regulates hepatocyte iNOS expression through an Akt-mediated signaling mechanism that is independent of MAPK P44/42. (c) 2010 Elsevier B.V. All rights reserved.

关键词： Akt Nitric oxide synthase Cyclic adenosine monophosphate Hepatocyte

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Open-loop and optimal control of cylinder wake via electromagnetic fields

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Chinese Science Bulletin 2008年第19期53卷 2946-2952页

作者： zhang Hui FAN baochun CHEN ZhiHua DONG Gang ZHOU BenMou Laboratory of Transient Physics Nanjing University of Science and Technology Nanjing 210094 China

The experimental and numerical investigations on electromagnetic control of cylinder wake have been performed in this paper. Experiments were conducted in a rotating annular tank filled with a low-conducting electrolyte. A cylinder with an electromagnetic actuator mounted on the surface was placed into the electrolyte. Force measurements have been carried out by strain gages attached to a fixed beam to which the hydrofoil is suspended and flow fields are visualized by dye markers. Based on the Navier-Stokes equations considering the electromagnetic body force, i.e. Lorentz force, in the ex- ponential-polar coordinates, the numerical investigations were carried out by means of an Alterna- tive-Direction Implicit algorithm and a Fast Fourier Transform algorithm. Experimental results have shown the same tendency with the numerical results. For the constant Lorentz forces, called open-loop control, the vortex shedding was fully suppressed. Meanwhile, the weak street disappeared and the drag force was reduced. Based on the Navier-Stokes equations, an adjoint-based ensemble optimiza- tion of control algorithms was developed and adjoint equations in the exponential-polar coordinates were derived. The equations were solved by numerical algorithm as mentioned above. The evolutions of the flow field in the control process were discussed according to the calculated variable optimal interaction parameters.

关键词：圆柱尾流电磁流最佳控制设计电磁域

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Variations in Main Flavor Compounds of Freshly Distilled Brandy during the Second Distillation

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INTERNATIONAL JOURNAL OF FOOD ENGINEERING 2014年第4期10卷 809-820页

作者： Zhao, Yuping Tian, Tiantian Li, Jiming zhang, baochun Yu, Ying Wang, Yangyang Niu, Hao Yantai Univ Coll Life Sci Yantai 264005 Shandong Peoples R China Changyu Pioneer Wine Co Ltd Ctr Technol Yantai 264001 Shandong Peoples R China

The present study investigated the variations in main flavor compounds of a Chinese brandy during the second distillation process using headspace-solid-phase microextraction coupled with gas chromatography-mass spectrometry. A total of 97 volatile compounds involving esters, alcohols, aldehydes, ketones, furans, benzene derivatives and terpenes were quantified, and 28 components were identified as key ingredients. By monitoring the second distillation process, it was found that most ethyl esters (ethyl hexanoate, ethyl octanoate, etc.), alcohols (3-methylbutanol, etc.), terpenes (linalool, etc.), acetaldehyde and ionone all had higher values at the beginning of the distillation, but declined gradually or sharply along with the distillation process. However, two esters (ethyl lactate and diethyl succinate), acids (acetic acid, hexanoic acid), benzene derivatives (2-phenylethanol, etc.) and furan (furfural) showed lower levels when the distillation was just started, and gradually increased, accumulating as a large quantity at the end of the distillation.

关键词： brandy gas chromatography-mass spectrometry headspace solid phase micro-extraction main flavor compounds second distillation variation

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