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Pathophysiology and Therapy of Bladder Function Disorders and Cystitis
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Pathophysiology and Therapy of Bladder Function Disorders and Cystitis

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (15 October 2023) | Viewed by 18240

Special Issue Editor

Dr. Wei-Chia Lee

E-Mail Website
Guest Editor
Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
Interests: cystitis; bladder pain syndrome; urinary tract infection
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Patients with bladder disorders are overlooked in clinic today. The current knowledge of the pathophysiology of bladder disorders may not fully allow differential diagnosis of lower urinary tract symptoms, let alone treatment. Through investigating the molecular mechanisms in humans and animal models, appropriate therapeutic strategies could be applied on those patients with bladder disorders and cystitis. In this Special Issue, we encourage researchers to report the pathophysiology and treatment strategies in functional bladder disorders through an overactive bladder to an underactive bladder. This Special Issue will give an overview of recent advances in difficult issues of cystitis, such as intractable bacterial cystitis, chronic pelvic pain syndrome, ketamine cystitis, interstitial cystitis, and irradiation cystitis. The goal of this issue is to be beneficial for scientists, urologists, and physicians. Original articles and comprehensive reviews in the topic that focus on molecular research are warmly welcomed.

Potential topics include but are not limited to:

  • antimicrobial strategies for intractable cystitis;
  • microbiota-related functional bladder disorders;
  • metabolic syndrome-associated overactive bladder;
  • chronic bladder ischemia and bladder disorders;
  • the pathophysiology and treatment strategies of ketamine cystitis;
  • novel treatments in interstitial cystitis;
  • regeneration medicine in underactive bladder;
  • shock wave therapy for chronic pelvic pain syndrome.

Prof. Dr. Wei-Chia Lee
Guest Editor

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • bladder ischemia
  • bladder pain syndrome
  • interstitial cystitis
  • irradiation cystitis
  • ketamine cystitis
  • microbiota
  • overactive bladder
  • underactive bladder
  • botulinum toxin for bladder disorders

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Published Papers (5 papers)

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Research

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15 pages, 3549 KiB  
Article
The Assessment of the Efficacy of Imperatorin in Reducing Overactive Bladder Symptoms
by Paulina Iwaniak, Piotr Dobrowolski, Jan Wróbel, Tomasz Kluz, Artur Wdowiak, Iwona Bojar, Klaudia Stangel-Wójcikiewicz, Ewa Poleszak, Artur Jakimiuk, Marcin Misiek, Łukasz Zapała and Andrzej Wróbel
Int. J. Mol. Sci. 2023, 24(21), 15793; https://doi.org/10.3390/ijms242115793 - 31 Oct 2023
Viewed by 1670
Abstract
Overactive bladder syndrome (OAB) is a prevalent condition that affects the elderly population in particular and significantly impairs quality of life. Imperatorin, a naturally occurring furocoumarin, possesses diverse pharmacological properties that warrant consideration for drug development. The aim of this study was to [...] Read more.
Overactive bladder syndrome (OAB) is a prevalent condition that affects the elderly population in particular and significantly impairs quality of life. Imperatorin, a naturally occurring furocoumarin, possesses diverse pharmacological properties that warrant consideration for drug development. The aim of this study was to investigate the potential of imperatorin (IMP) to attenuate the cystometric and biochemical changes typically associated with retinyl acetate-induced overactive bladder (OAB) and to assess its viability as a pharmacological intervention for OAB patients. A total of 60 rats were divided into four groups: I—control, II—rats with rapamycin (RA)-induced OAB, III—rats administered IMP at a dose of 10 mg/kg/day, and IV—rats with RA-induced OAB treated with IMP. IMP or vehicle were injected intraperitoneally for 14 days. The cystometry and assessment of bladder blood flow were performed two days after the last dose of IMP. The rats were then placed in metabolic cages for 24 h. Urothelial thickness measurements and biochemical analyses were performed. Intravesical infusion of RA induced OAB. Notably, intraperitoneal administration of imperatorin had no discernible effect on urinary bladder function and micturition cycles in normal rats. IMP attenuated the severity of RA-induced OAB. RA induced increases in urothelial ATP, calcitonin gene-related peptide (CGRP), organic cation transporter 3 (OCT3), and vesicular acetylcholine transporter (VAChT), as well as significant c-Fos expression in all micturition areas analyzed, which were attenuated by IMP. Furthermore, elevated levels of Rho kinase (ROCK1) and VAChT were observed in the detrusor, which were reversed by IMP in the context of RA-induced OAB in the urothelium, detrusor muscle, and urine. Imperatorin has a mitigating effect on detrusor overactivity. The mechanisms of action of IMP in the bladder appear to be diverse and complex. These findings suggest that IMP may provide protection against RA-induced OAB and could potentially develop into an innovative therapeutic strategy for the treatment of OAB. Full article
(This article belongs to the Special Issue Pathophysiology and Therapy of Bladder Function Disorders and Cystitis)
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34 pages, 22996 KiB  
Article
Effects of Therapeutic Platelet-Rich Plasma on Overactive Bladder via Modulating Hyaluronan Synthesis in Ovariectomized Rat
by Jian-He Lu, Kuang-Shun Chueh, Tai-Jui Juan, Jing-Wen Mao, Rong-Jyh Lin, Yi-Chen Lee, Mei-Chen Shen, Ting-Wei Sun, Hung-Yu Lin and Yung-Shun Juan
Int. J. Mol. Sci. 2023, 24(9), 8242; https://doi.org/10.3390/ijms24098242 - 4 May 2023
Cited by 3 | Viewed by 2395
Abstract
Postmenopausal women who have ovary hormone deficiency (OHD) may experience urological dysfunctions, such as overactive bladder (OAB) symptoms. This study used a female Sprague Dawley rat model that underwent bilateral ovariectomy (OVX) to simulate post-menopause in humans. The rats were treated with platelet-rich [...] Read more.
Postmenopausal women who have ovary hormone deficiency (OHD) may experience urological dysfunctions, such as overactive bladder (OAB) symptoms. This study used a female Sprague Dawley rat model that underwent bilateral ovariectomy (OVX) to simulate post-menopause in humans. The rats were treated with platelet-rich plasma (PRP) or platelet-poor plasma (PPP) after 12 months of OVX to investigate the therapeutic effects of PRP on OHD-induced OAB. The OVX-treated rats exhibited a decrease in the expression of urothelial barrier-associated proteins, altered hyaluronic acid (hyaluronan; HA) production, and exacerbated bladder pathological damage and interstitial fibrosis through NFƘB/COX-2 signaling pathways, which may contribute to OAB. In contrast, PRP instillation for four weeks regulated the inflammatory fibrotic biosynthesis, promoted cell proliferation and matrix synthesis of stroma, enhanced mucosal regeneration, and improved urothelial mucosa to alleviate OHD-induced bladder hyperactivity. PRP could release growth factors to promote angiogenic potential for bladder repair through laminin/integrin-α6 and VEGF/VEGF receptor signaling pathways in the pathogenesis of OHD-induced OAB. Furthermore, PRP enhanced the expression of HA receptors and hyaluronan synthases (HAS), reduced hyaluronidases (HYALs), modulated the fibroblast-myofibroblast transition, and increased angiogenesis and matrix synthesis via the PI3K/AKT/m-TOR pathway, resulting in bladder remodeling and regeneration. Full article
(This article belongs to the Special Issue Pathophysiology and Therapy of Bladder Function Disorders and Cystitis)
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13 pages, 1045 KiB  
Article
Sensory Receptor, Inflammatory, and Apoptotic Protein Expression in the Bladder Urothelium of Patients with Different Subtypes of Interstitial Cystitis/Bladder Pain Syndrome
by Yuan-Hong Jiang, Jia-Fong Jhang, Lori A. Birder and Hann-Chorng Kuo
Int. J. Mol. Sci. 2023, 24(1), 820; https://doi.org/10.3390/ijms24010820 - 3 Jan 2023
Cited by 7 | Viewed by 2160
Abstract
The aim of this study was to investigate the expression levels of sensory receptors, inflammatory proteins, and pro-apoptotic proteins in the urothelium of non-Hunner’s interstitial cystitis (NHIC) bladders of patients with different clinical and cystoscopic phenotypes. The urothelia from the bladders of 52 [...] Read more.
The aim of this study was to investigate the expression levels of sensory receptors, inflammatory proteins, and pro-apoptotic proteins in the urothelium of non-Hunner’s interstitial cystitis (NHIC) bladders of patients with different clinical and cystoscopic phenotypes. The urothelia from the bladders of 52 NHIC patients were harvested. The expression of sensory receptors, including TRPV1, TRPV4, TRPA1, H1-receptors, and sigma-1 receptors; the inflammatory proteins p38 and tryptase; and the pro-apoptotic proteins, such as caspase-3, BAD, and BAX in the urothelium, were investigated using immunohistochemistry and Western blotting. We compared the expression levels of these proteins in NHIC subtypes according to IC symptom scores, visual analog scores of bladder pain, maximal bladder capacity, glomerulation grades, and combined maximal bladder capacity and glomerulations after cystoscopic hydrodistention. The expression levels of TRPV1, TRPV4, sigma-1, P38, tryptase, caspase-3, and BAD were significantly increased in the urothelium of IC/BPS patients compared with the expression levels in the controls. TRPV1 was significantly associated with IC symptom severity. However, no significant differences in sensory receptor expression in the IC/BPS bladders with different bladder conditions were detected. Inflammatory and pro-apoptotic protein expression levels in the urothelium were similar among the IC/BPS subgroups. This study concluded that IC/BPS patients with frequency and bladder pain complaints have higher levels of urothelial sensory receptors, and inflammatory and pro-apoptotic proteins. The expression levels of these sensory receptors, inflammatory proteins, and pro-apoptotic proteins are not significantly different among IC/BPS bladders with different conditions. Full article
(This article belongs to the Special Issue Pathophysiology and Therapy of Bladder Function Disorders and Cystitis)
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Review

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26 pages, 400 KiB  
Review
Underactive Bladder and Detrusor Underactivity: New Advances and Prospectives
by Jiaxin Wang, Lida Ren, Xinqi Liu, Jihong Liu and Qing Ling
Int. J. Mol. Sci. 2023, 24(21), 15517; https://doi.org/10.3390/ijms242115517 - 24 Oct 2023
Cited by 9 | Viewed by 5959
Abstract
Underactive bladder (UAB) is a prevalent but under-researched lower urinary tract symptom that typically occurs alongside detrusor underactivity (DU). Unlike UAB, DU is a urodynamic diagnosis which the International Continence Society (ICS) defines as “a contraction of reduced strength and/or duration, resulting in [...] Read more.
Underactive bladder (UAB) is a prevalent but under-researched lower urinary tract symptom that typically occurs alongside detrusor underactivity (DU). Unlike UAB, DU is a urodynamic diagnosis which the International Continence Society (ICS) defines as “a contraction of reduced strength and/or duration, resulting in prolonged bladder emptying and/or a failure to achieve complete bladder emptying within a normal time span”. Despite the widespread prevalence of UAB/DU, there are significant gaps in our understanding of its pathophysiological mechanisms, diagnosis, and treatment compared with overactive bladder (OAB) and detrusor overactivity (DO). These gaps are such that clinicians regard UAB/DU as an incurable condition. In recent years, the understanding of UAB has increased. The definition of UAB has been clarified, and the diagnostic criteria for DU have been considered more comprehensively. Meanwhile, a number of non-invasive diagnostic methods have also been reported. Clinical trials involving novel drugs, electrical stimulation, and stem cell therapy have shown promising results. Therefore, this review summarizes recent reports on UAB and DU and highlights the latest advances in their diagnosis and treatment. Full article
(This article belongs to the Special Issue Pathophysiology and Therapy of Bladder Function Disorders and Cystitis)
20 pages, 1175 KiB  
Review
Emerging Non-Antibiotic Options Targeting Uropathogenic Mechanisms for Recurrent Uncomplicated Urinary Tract Infection
by Yu-Chen Chen, Wei-Chia Lee and Yao-Chi Chuang
Int. J. Mol. Sci. 2023, 24(8), 7055; https://doi.org/10.3390/ijms24087055 - 11 Apr 2023
Cited by 11 | Viewed by 5294
Abstract
Urinary tract infections (UTIs) are the most frequent bacterial infections in the clinical setting. Even without underlying anatomic or functional abnormalities, more than 40% of women experience at least one UTI in their lifetime, of which 30% develop recurrent UTIs (rUTIs) within 6 [...] Read more.
Urinary tract infections (UTIs) are the most frequent bacterial infections in the clinical setting. Even without underlying anatomic or functional abnormalities, more than 40% of women experience at least one UTI in their lifetime, of which 30% develop recurrent UTIs (rUTIs) within 6 months. Conventional management with antibiotics for rUTIs may eventually lead to the development of multidrug-resistant uropathogens. Targeting of the pathogenicity of rUTIs, the evolution of uropathogenic Escherichia coli (UPEC), and inadequate host defenses by immune responses should be explored to provide non-antibiotic solutions for the management of rUTIs. The adaptive evolution of UPEC has been observed in several aspects, including colonization, attachment, invasion, and intracellular replication to invade the urothelium and survive intracellularly. Focusing on the antivirulence of UPEC and modulating the immunity of susceptible persons, researchers have provided potential alternative solutions in four categories: antiadhesive treatments (i.e., cranberries and D-mannose), immunomodulation therapies, vaccines, and prophylaxis with topical estrogen therapy and probiotics (e.g., Lactobacillus species). Combination therapies targeting multiple pathogenic mechanisms are expected to be a future trend in UTI management, although some of these treatment options have not been well established in terms of their long-term efficacy. Additional clinical trials are warranted to validate the therapeutic efficacy and durability of these techniques. Full article
(This article belongs to the Special Issue Pathophysiology and Therapy of Bladder Function Disorders and Cystitis)
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