Zong-Sheng Wu et al., 2024: Extracorporeal shock wave therapy modulates miRNA expression, reduces inflammation, and improves liposome retention in a rat model of cyclophosphamide induced cystitis-experimental studies
Zong-Sheng Wu 1 2, Wei-Chia Lee 1 2, Michael B Chancellor 3, Hung-Jen Wang 1 2, Chao-Cheng Huang 4, Yao-Chi Chuang 1 2 5
1Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
2Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan Kaohsiung 833, Taiwan.
3Department of Urology, Beaumont Health System, Oakland University William Beaumont School of Medicine, Royal Oak, MI.
4Department of Pathology5, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
5School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung 833, Taiwan.
Abstract
no abstract available
Int J Surg. 2024 Jul 22. doi: 10.1097/JS9.0000000000001961. Online ahead of print.
PMID: 39037744
Comments 1
Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic condition characterized by bladder pain, increased urinary urgency, and frequency without an identifiable cause. Traditional treatments face limitations, and there is an unmet need for effective therapies. Low Energy Shock Waves (LESW) have demonstrated anti-inflammatory effects and potential symptom relief in IC/BPS. This study explores the mechanisms of LESW, focusing on its effects on inflammation, microRNAs (miRNAs), and mu-opioid receptor (MOR) expression, as well as its ability to enhance intravesical drug retention.
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Methods: The authors used an animal model in combination with a drug retention study.. Female rats were treated with cyclophosphamide (CYP) to induce bladder inflammation. LESW (100 or 300 pulses) was applied to the bladder region, and tissues were analyzed for inflammation markers, MOR expression, miRNA levels, and protein changes.
Liposomes were instilled into the bladder, and fluorescence imaging tracked their retention over two hours to evaluate LESW’s effects on drug retention.
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Results: The study showed three important effects on the induced cystitis
Anti-Inflammatory Effects:
o LESW significantly reduced inflammatory cell infiltration and cytokine levels (IL-1β, IL-6) induced by CYP.
o It increased the expression of tight junction proteins (ZO-1, E-cadherin), which help maintain bladder lining integrity.
MicroRNA Modulation:
o CYP increased miR-146b-5p and miR-21-5p levels, associated with inflammation. LESW treatment significantly reduced these miRNAs, suggesting a role in mitigating bladder inflammation.
Mu-Opioid Receptor (MOR) Regulation:
o MOR expression, elevated in both bladder and spinal tissues after CYP treatment, was lowered by LESW, indicating potential modulation of pain and inflammation pathways.
Improved Drug Retention: Moreover, they found that LESW prolonged bladder retention of liposomes, potentially by modulating tight junction proteins, enhancing the therapeutic effects of intravesical drug delivery.
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Discussion:
LESW demonstrated significant therapeutic potential for IC/BPS by reducing bladder inflammation, altering molecular markers (miRNAs and MOR), and improving drug retention. These findings align with prior research showing LESW’s benefits in pain reduction and its ability to enhance drug delivery.
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Conclusion:
LESW offers a promising non-invasive approach for IC/BPS management. Its anti-inflammatory properties, molecular modulation, and enhanced drug retention suggest potential as a standalone or adjunctive therapy. Based on this animal study, further clinical trials are warranted to confirm its efficacy and optimize treatment protocols.
Jens Rassweiler