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NFK prevent postoperative abdominal adhesion through downregulating the TGF-β1 signaling pathway

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Abstract

Background

Postoperative abdominal adhesions (PAAs) represent a frequent condition occurring in more than 90% of patients undergoing abdomen and pelvic surgeries, which can cause chronic abdominal pain, female infertility, and repeated bowel obstruction, requiring repetitive surgical interventions causing morbidity and mortality, as well as high costs. It is therefore of paramount clinical importance and significance to develop practical and reliable strategies for preventing the occurrence of PAAs.

Methods and Results

In this study, we demonstrated that Nianfukang (NFK, composed of polyethylene glycol 1450 and diclofenac sodium) is highly effective in preventing PAAs, likely by reducing leukocytes and inflammatory factors in the abdominal cavity, and inhibiting intestinal fibrosis in a rat model of PAAs induced by postoperative cecum scraping. We further uncovered that NFK downregulates the expression of TGF-β1, a key factor for adhesion formation, to suppress the TGF-β1/TGF-βRIII/Smad2 signaling pathway, thereby inhibiting the proliferation and migration of fibroblasts and provided evidences for the involvement of the TGF-β1/TGF-βRIII/Smad2 axis in the prevention of PAAs in normal human colon fibroblast CCD-18Co.

Conclusions

Our findings support NFK as a potential anti-adhesive product that has the advantages of significant effectiveness, safety profile, and low cost, as well as clear mechanism of action.

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Acknowledgements

This project was supported by the Project of Central Guidance for the Development of Local Science and Technology (Grant No. ZY16A07), Research and Develop Project of Heilongjiang Province for Applied Technology (Grant No. GA14C102), the National Natural Science Foundation of China (81730012), and the CAMS Innovation Fund for Medical Sciences (CIFMS, 2019-I2M-5-078).

Funding

This project was supported by the Project of Central Guidance for the Development of Local Science and Technology (Grant No. ZY16A07), Research and Develop Project of Heilongjiang Province for Applied Technology (Grant No. GA14C102), the National Natural Science Foundation of China (81730012), and the CAMS Innovation Fund for Medical Sciences (CIFMS, 2019-I2M-5-078).

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Author notes

  1. Xin Zhao and Xianmei Piao have equal contributions to this work.

Authors and Affiliations

  1. Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China

    Xin Zhao, Xianmei Piao, Bin Liu, Rumeng Xie, Tingting Zhan, Min Liang, Jiaying Tian, Ruishuai Wang, Chao Chen, Jiuxin Zhu, Yan Zhang & Baofeng Yang

  2. Research Unit of Noninfectious Chronic Diseases in Frigid Zone (2019RU070), Chinese Academy of Medical Sciences, 150081, Harbin, China

    Baofeng Yang

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  1. Xin Zhao
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Contributions

XZ, BY and YZ contributed to the conception of the study; BL, RX, ML performed the experiment; XP, JZ contributed significantly to analysis and manuscript preparation; CC, RW performed the data analyses and wrote the manuscript; JT and TZ helped perform the analysis with constructive discussions.

Corresponding authors

Correspondence to Yan Zhang or Baofeng Yang.

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Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

The experimental protocol involving the animals was designed to minimize pain and discomfort to the animals in accordance with the guidelines of the China Council on Animal Care and Use and was approved by The Animal Ethical Committee of Harbin Medical University.

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Zhao, X., Piao, X., Liu, B. et al. NFK prevent postoperative abdominal adhesion through downregulating the TGF-β1 signaling pathway. Mol Biol Rep 50, 279–288 (2023). https://doi.org/10.1007/s11033-022-07795-2

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