Tingting Xu

Wenzhou Medical University

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Shijie Zhang

First Affiliated Hospital of Zhengzhou University

Qi Wang

Guangzhou University of Chinese Medicine

Zhanpeng Yan

Nanjing University of Chinese Medicine

Yunke Guo

Nanjing University of Chinese Medicine

Fangshi Zhu

Nanjing University of Chinese Medicine

Youjuan Zhu

Nanjing University of Chinese Medicine

Qiuxiang Shen

Zhejiang University

Shenghong Ju

Zhongda Hospital Southeast University

Jinfeng Su

Shenzhen Children's Hospital

Shijia Liu

Nanjing University of Chinese Medicine

Cooperative Institutions

Nanjing University of Chinese Medicine

Sun Yat-sen University

Chinese Academy of Sciences

Fudan University

Guangzhou University of Chinese Medicine

Dalian Medical University

Southern Medical University

Chinese Academy of Medical Sciences & Peking Union Medical College

Wenzhou Medical University

Zhongshan Hospital

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Dynamic change of MMP-9 in diabetic stroke visualized by optical imaging and treated with CD28 superagonist

Biomaterials Science (2021)

Yu Cai Shou Leng Yuanyuan Ma Tingting Xu Di Chang

Type 2 diabetes mellitus is associated with an increased risk for stroke and unfavorable outcomes following stroke. Matrix metalloproteinase-9 (MMP-9) is a potential contributor to the poor prognosis of diabetic ischemic stroke. Investigations on diabetic stroke are limited by the lack of non-invasive imaging techniques. In this study, we report a fast and ultra-sensitive MMP-activatable optical imaging probe (MMP-P12) to achieve non-invasive and real-time visualization of the dynamic expression of MMP-9 in diabetic stroke. Moreover, by using this probe, we aim to detect the therapeutic efficacy of CD28 SA in diabetic stroke. Serial near-infrared fluorescence (NIRF) imaging was performed on wild-type and STZ-induced diabetic mice after MMP-P12 probe injection on days 1, 3, and 7 post ischemic stroke. The dynamic change in MMP-9 expression after CD28 SA treatment was also imaged on days 1, 3, and 7 post stroke and confirmed by immunohistochemistry staining and western blotting. NIRF imaging showed that diabetic stroke mice presented a trend of higher levels of MMP-9. CD28 SA treatment significantly downregulated the expression of MMP-9 on day 7 post stroke. Glucose also had a downward trend in CD28 SA treated diabetic stroke mice. In conclusion, our data suggest that MMP-P12 probe successfully detect the dynamic change of MMP-9 in diabetic stroke by utilizing optical imaging. CD28 SA treatment decreased the expression of MMP-9 and could be a promising therapeutic strategy for the treatment of diabetic stroke.

Stroke

10.1039/d0bm02014a

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Bushen-Yizhi formula ameliorates cognitive dysfunction through SIRT1/ER stress pathway in SAMP8 mice

Oncotarget (2017)

Shijie Zhang Tingting Xu Li Lin Yu-Min Xu Zi-Ling Qu

The Chinese formula Bushen-Yizhi (BSYZ) has been reported to ameliorate cognitive dysfunction. However the mechanism is still unclear. In this study, we employ an aging model, SAMP8 mice, to explore whether BSYZ could protect dementia through SIRT1/endoplasmic reticulum (ER) stress pathway. Morris water maze and the fearing condition test results show that oral administration of BSYZ (1.46 g/kg/d, 2.92 g/kg/d and 5.84 g/kg/d) and donepezil (3 mg/kg/d) shorten the escape latency, increase the crossing times of the original position of the platform and the time spent in the target quadrant, and increase the freezing time. BSYZ decreases the activity of acetylcholinesterase (AChE), and increases the activity of choline acetyltransferase (ChAT) and the concentration of acetylcholine (Ach) in both hippocampus and cortex. In addition, western blot results (Bcl-2, Bax and Caspase-3) and TUNEL staining show that BSYZ prevents neuron from apoptosis, and elevates the expression of neurotrophic factors, including nerve growth factor (NGF), postsynapticdensity 95 (PSD95) and synaptophysin (SYN), in both hippocampus and cortex. BSYZ also increases the protein expression of SIRT1 and alleviates ER stress-associated proteins (PERK, IRE-1α, eIF-2α, BIP, PDI and CHOP). These results indicate that the neuroprotective mechanism of BSYZ might be related with SIRT1/ER stress pathway.

Synaptophysin

10.18632/oncotarget.17638

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Citations (29)

Aripiprazole augmentation in managing comorbid obsessive–compulsive disorder and bipolar disorder: a case with suicidal attempts

Neuropsychiatric Disease and Treatment (2016)

Jianbo Lai Qiaoqiao Lu Peng Zhang Tingting Xu Yi Xu

Comorbid obsessive-compulsive disorder (OCD) and bipolar disorder (BD) have long been an intractable problem in clinical practice. The increased risk of manic/hypomanic switch hinders the use of antidepressants for managing coexisting OCD symptoms in BD patients. We herein present a case of a patient with BD-OCD comorbidity, who was successfully treated with mood stabilizers and aripiprazole augmentation. The young female patient reported recurrent depressive episodes and aggravating compulsive behaviors before hospitalization. Of note, the patient repetitively attempted suicide and reported dangerous driving because of intolerable mental sufferings. The preexisting depressive episode and OCD symptoms prompted the use of paroxetine, which consequently triggered the manic switching. Her diagnosis was revised into bipolar I disorder. Minimal response with mood stabilizers prompted the addition of aripiprazole (a daily dose of 10 mg), which helped to achieve significant remission in emotional and obsessive-compulsive symptoms. This case highlights the appealing efficacy of a small dose of aripiprazole augmentation for treating BD-OCD comorbidity. Well-designed clinical trials are warranted to verify the current findings.

Aripiprazole

Paroxetine

Bipolar I disorder

10.2147/ndt.s122316

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Tetrahydroisoquinoline-7-carboxamide Derivatives as New Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors

ACS Medicinal Chemistry Letters (2017)

Zhen Wang Yali Zhang Sergio G. Bartual Jinfeng Luo Tingting Xu

Acute lung injury (ALI) is a deadly symptom for serious lung inflammation. Discoidin Domain Receptor 1 (DDR1) is a new potential target for anti-inflammatory drug discovery. A new selective tetrahydroisoquinoline-7-carboxamide based DDR1 inhibitor 7ae was discovered to tightly bind the DDR1 protein and potently inhibit its kinase function with a Kd value of 2.2 nM and an IC50 value of 6.6 nM, respectively. The compound dose-dependently inhibited lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) release in mouse primary peritoneal macrophages (MPMs). In addition, 7ae also exhibited promising in vivo anti-inflammatory effects in a LPS-induced mouse ALI model. To the best of our knowledge, this is the first "proof of concept" investigation on the potential application of a small molecule DDR1 inhibitor to treat ALI.

Discoidin domain

DDR1

Tetrahydroisoquinoline

10.1021/acsmedchemlett.6b00497

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Citations (34)

[Prognostic analysis of patients with mutations in the JAK/STAT signaling pathway in adult acute lymphoblastic leukemia].

PubMed (2021)

Wenya Fan Tingting Xu Jiacheng Guo Y F Li Zhongxing Jiang

10.3760/cma.j.issn.0253-2727.2021.07.011

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Discovery and Optimization of Novel Nonbile Acid FXR Agonists as Preclinical Candidates for the Treatment of Inflammatory Bowel Disease

Journal of Medicinal Chemistry (2024)

Yuan Li Tingting Xu Yue Zhao Hui Zhang Zesheng Liu

Inflammatory bowel disease (IBD) is a multifactorial chronic inflammation of the intestine and has become a global public health concern. A farnesoid X receptor (FXR) was recently reported to play a key role in hepatic-intestinal circulation, intestinal metabolism, immunity, and microbial regulation, and thus, it becomes a promising therapeutic target for IBD. In this study, we identified a series of nonbile acid FXR agonists, in which 33 novel compounds were designed and synthesized by the structure-based drug design strategy from our previously identified hit compound. Compound 33 exhibited a potent FXR agonistic activity, high intestinal distribution, good anti-inflammatory activity, and the ability to repair the colon epithelium in a DSS-induced acute enteritis model. Based on the results of RNA-seq analysis, we further investigated the therapeutic potential of the combination of compound 33 with 5-ASA. Overall, the results indicated that compound 33 is a promising drug candidate for IBD treatment.

Farnesoid X receptor

Intestinal epithelium

10.1021/acs.jmedchem.3c02304

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Citations (2)

hnRNPA2/B1 activates cyclooxygenase‐2 and promotes tumor growth in human lung cancers

Molecular Oncology (2015)

Xuan Yang Jingshu Wang Ban Li-ying Jian-Jun Lu Canhui Yi

Cyclooxygenase‐2 (COX‐2) is highly expressed in tumor cells and has been regarded as a hallmarker for cancers, but the excise regulatory mechanism of COX‐2 in tumorigenesis remains largely unknown. Here, we pulled down and identified a novel COX‐2 regulator, heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1), which could specifically bind to COX‐2 core promoter and regulate tumor growth in non‐small‐cell lung cancers (NSCLCs). Knockdown of hnRNPA2/B1 by shRNA or siRNA downregulated COX‐2 expression and prostaglandin E2 (PGE2) production, and suppressed tumor cell growth in NSCLC cells in vitro and in vivo. Conversely, overexpression of hnRNPA2/B1 up‐regulated the levels of COX‐2 and PGE2 and promoted tumor cell growth. We also showed that hnRNPA2/B1 expression was positively correlated with COX‐2 expression in NSCLC cell lines and tumor tissues, and the up‐regulated expression of hnRNPA2/B1 and COX‐2 predicted worse prognosis in NSCLC patients. Furthermore, we demonstrated that the activation of COX‐2 expression by hnRNPA2/B1 was mediated through the cooperation with p300, a transcriptional co‐activator, in NSCLC cells. The hnRNPA2/B1 could interact with p300 directly and be acetylated by p300. Exogenous overexpression of p300, but not its histone acetyltransferase (HAT) domain deletion mutation, augmented the acetylation of hnRNPA2/B1 and enhanced its binding on COX‐2 promoter, thereby promoted COX‐2 expression and lung cancer cell growth. Collectively, our results demonstrate that hnRNPA2/B1 promotes tumor cell growth by activating COX‐2 signaling in NSCLC cells and imply that the hnRNPA2/B1/COX‐2 pathway may be a potential therapeutic target for human lung cancers.

10.1016/j.molonc.2015.11.010

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Citations (42)

Nontargeted serum metabolomics analysis and potential biomarkers for systemic lupus erythematosus

Microchemical Journal (2021)

Yingzhuo Wang Feng Guo Donglin Hao Yunke Guo Tingting Xu

Fatty Acid Metabolism

Pyrimidine metabolism

10.1016/j.microc.2021.106677

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Citations (6)

Natural autophagy modulators in non-communicable diseases: from autophagy mechanisms to therapeutic potential

Acta Pharmacologica Sinica (2024)

Tingting Xu Ying-yi Deng Xi‐Yong Yu Min Li Yuanyuan Fu

10.1038/s41401-024-01356-y

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Citations (1)

The Prognostic Significance of Postoperative Adjuvant Chemotherapy in the Population Aged 75 Years and Older with Stage II–III Colorectal Cancer: A Retrospective Multi-Center Cohort Study

International Journal of General Medicine (2023)

Lizhu Liu Xiaolin Pang Ke Zhao Yaxue Chen Yanli Li

Background: It is common for elderly patients to be underrepresented in clinical trials for cancer, which can result in a lack of efficacy data and unclear criteria to guide treatment decisions for clinical doctors. Therefore, one of the common challenges in oncology treatment is determining the extent to which patients aged 75 and older have benefited from postoperative chemotherapy. Purpose: The study aimed to explore the effect of adjuvant chemotherapy (AC) on 3-year recurrence-free survival (RFS) after curative resection in patients aged 75 years and older with stage II–III colorectal cancer (CRC). Methods: The retrospective cohort analysis was performed on patients with stage II–III CRC who received curative resection at three cancer centers in China between 2008 and 2017. Kaplan-Meier curves and Multivariable Cox regression models were used to analyze the impact of AC on RFS in patients. Finally, propensity-score matching was used to reduce selection bias and confounding factors in patients aged 75 years and older with stage II–III CRC. Results: A total of 2885 patients were included (1729 (59.9%) male; 1312 (61.5%) received AC). The pre-matching cohort was comprised of 151 patients aged 75 years and older (median age (IQR)77.00 (76.00, 79.00); 97 (64.2%) male, 51 (72.9%) received AC). Age ( P =0.001), postoperative carcinoembryonic antigen (CEA)( P =0.02) level were associated with prognosis. But AC was not associated with 3-year RFS (HR, 1.27; 95% CI, 0.80– 2.0; log-rank P =0.37). After a predisposition 1: 1 match (with or without AC, n = 42), AC remains uncorrelated with 3-year RFS (HR, 1.39; 95% CI, 0.52– 3.70; log-rank P =0.66). Conclusion: Patients over the age of 75 with stage II–III CRC who receive AC or do not face the same risk of postoperative recurrence. As a result, patients with stage II–III postoperative adjuvant chemotherapy can make an informed decision regarding whether they want to undergo chemotherapy based on their age and reduce the unnecessary side effects of chemotherapy. Keywords: colorectal cancer, adjuvant chemotherapy, recurrence-free survival, prognosis

Carcinoembryonic antigen

10.2147/ijgm.s420024

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Citations (1)