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Molecular Diagnosis of Pathologies of the Lower Urinary Tract

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A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Medical Biology".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 11422

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Special Issue Editors

Dr. John S. Young

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Guest Editor

Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK
Interests: urology; physiology; pathology; biomarkers; urine; blood; saliva; diagnosis; prognosis; prediction; molecular biology; multivariate statistics; biomarker discovery; analytical biochemistry; cellular biology; translational research; applied research

Prof. Dr. En Meng

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Co-Guest Editor

Division of Urology, Department of Surgery, Tri-service General Hospital, Taipei City 11490, Taiwan
Interests: general urology; functional urology; urodynamics; female urology; chronic cystitis; ketamine uropathy

Special Issue Information

Dear Colleagues,

Despite the high prevalence and immense burden of pathologies of the lower urinary tract, there remains the significant clinical challenge of differentiating the basis of overlapping urinary symptoms in order to ensure appropriate intervention and symptom relief.

There are many challenges to achieving accurate diagnosis of pathologies of the lower urinary tract, including the complexity of patient presentation; the low diagnostic accuracy of methods used in primary care; as well as inherent characteristics of methods used in the tertiary setting, which include expense, the invasive nature of methods, and requirement of a skilled operator. As such, time to diagnosis can be long, and delays in treatment can ultimately reduce the potential symptom relief.

This Special Issue welcomes the submission of original research (spanning discovery to translation), short communications, and review manuscripts focusing on novel methods for the diagnosis of non-oncological pathologies of the lower urinary tract. While focus will be on methods that could ultimately be developed for diagnosis in the clinical setting, studies concerning technologies and approaches employed in biomarker identification are welcomed. It is hoped that this Special Issue will address an area of clinical research that has been neglected but which is desperately needed.

Dr. John S. Young
Prof. Dr. En Meng
Guest Editors

Manuscript Submission Information

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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. Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

molecular biology
diagnostic biomarkers
urine
blood/serum
saliva
bioinformatics
lower urinary tract
overactive bladder
interstitial cystitis
urinary tract infection
benign prostatic hypertrophy

Published Papers (4 papers)

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Research

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11 pages, 904 KiB

Open AccessArticle

Contractile and Structural Properties of Detrusor from Children with Neurogenic Lower Urinary Tract Dysfunction

by Navroop Johal, Kevin X. Cao, Boyu Xie, Michael Millar, Reena Davda, Aamir Ahmed, Anthony J. Kanai, Dan N. Wood, Rita I. Jabr and Christopher H. Fry

Biology 2021, 10(9), 863; https://doi.org/10.3390/biology10090863 - 3 Sep 2021

Cited by 7 | Viewed by 2100

Abstract

Neurogenic lower urinary tract (NLUT) dysfunction in paediatric patients can arise after congenital or acquired conditions that affect bladder innervation. With some patients, urinary tract dysfunction remains and is more difficult to treat without understanding the pathophysiology. We measured in vitro detrusor smooth muscle function of samples from such bladders and any association with altered Wnt-signalling pathways that contribute to both foetal development and connective tissue deposition. A comparator group was tissue from children with normally functioning bladders. Nerve-mediated and agonist-induced contractile responses and passive stiffness were measured. Histology measured smooth muscle and connective tissue proportions, and multiplex immunohistochemistry recorded expression of protein targets associated with Wnt-signalling pathways. Detrusor from the NLUT group had reduced contractility and greater stiffness, associated with increased connective tissue content. Immunohistochemistry showed no major changes to Wnt-signalling components except down-regulation of c-Myc, a multifunctional regulator of gene transcription. NLUT is a diverse term for several diagnoses that disrupt bladder innervation. While we cannot speculate about the reasons for these pathophysiological changes, their recognition should guide research to understand their ultimate causes and develop strategies to attenuate and even reverse them. The role of changes to the Wnt-signalling pathways was minor. Full article

(This article belongs to the Special Issue Molecular Diagnosis of Pathologies of the Lower Urinary Tract)

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13 pages, 1724 KiB

Open AccessArticle

Programmed Cell Death Ligand 1 Expression in Circulating Tumor Cells as a Predictor of Treatment Response in Patients with Urothelial Carcinoma

by Pei-Jhang Chiang, Ting Xu, Tai-Lung Cha, Yi-Ta Tsai, Shu-Yu Liu, Sheng-Tang Wu, En Meng, Chih-Wei Tsao, Chien-Chang Kao, Chin-Li Chen, Guang-Huan Sun, Dah-Shyong Yu, Sun-Yran Chang and Ming-Hsin Yang

Biology 2021, 10(7), 674; https://doi.org/10.3390/biology10070674 - 16 Jul 2021

Cited by 5 | Viewed by 2186

Abstract

Programmed cell death ligand 1 (PD-L1) inhibitors are commonly used in treating advanced-stage urothelial carcinoma (UC). Therefore, this study evaluated the relationship between PD-L1 expression in circulating tumor cells (CTCs) and treatment response to PD-L1 inhibitors using blood samples collected from patients with UC (n = 23). Subsequently, PD-L1 expression and its clinical correlation were analyzed. All patients had CTCs before PD-L1 inhibitory treatment, of which 15 had PD-L1-positive CTCs. However, PD-L1-positive expression in CTCs was not correlated with PD-L1 expression in tumor biopsy samples. Patients with PD-L1-positive CTCs had better disease control (DC) rates than those without PD-L1-positive CTCs. Moreover, changes in the proportion of PD-L1-positive CTCs were associated with disease outcomes. Furthermore, the PD-L1-positive CTC count in 9 of 11 patients who achieved DC had significantly decreased (p = 0.01). In four patients with progressive disease, this was higher or did not change. PD-L1-positive CTCs at baseline could be used as a biomarker to identify patients suitable for PD-L1 blockade therapy. Dynamic changes in PD-L1-positive CTCs during the course of treatment are predictive factors of immunotherapy response and prognostic factors of disease control. Hence, PD-L1-positive CTCs could be employed as a real-time molecular biomarker for individualized immunotherapy. Full article

(This article belongs to the Special Issue Molecular Diagnosis of Pathologies of the Lower Urinary Tract)

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27 pages, 7425 KiB

Open AccessArticle

Autophagy Alters Bladder Angiogenesis and Improves Bladder Hyperactivity in the Pathogenesis of Ketamine-Induced Cystitis in a Rat Model

by Jian-He Lu, Yi-Hsuan Wu, Tai-Jui Juan, Hung-Yu Lin, Rong-Jyh Lin, Kuang-Shun Chueh, Yi-Chen Lee, Chao-Yuan Chang and Yung-Shun Juan

Biology 2021, 10(6), 488; https://doi.org/10.3390/biology10060488 - 30 May 2021

Cited by 9 | Viewed by 2772

Abstract

The present study attempts to elucidate whether autophagy alters bladder angiogenesis, decreases inflammatory response, and ameliorates bladder hyperactivity—thereby influencing bladder function in ketamine-induced cystitis (KIC). In our methodology, female Sprague-Dawley (S-D) rats were randomly divided into the control group, the ketamine group, the ketamine+rapamycin group, and the ketamine+wortmannin group. The bladder function, contractile activity of detrusor smooth muscle, distribution of autophagosome and autolysosome, total white blood cells (WBCs) and leukocyte differential counts, the expressions of autophagy-associated protein, angiogenesis markers, and signaling pathway molecules involved in KIC were tested, respectively. The data revealed that treatment with ketamine significantly results in bladder overactivity, enhanced interstitial fibrosis, impaired endothelium, induced eosinophil-mediated inflammation, swelling, and degraded mitochondria and organelles, inhibited angiogenesis, and elevated the phosphorylation of Akt. However, treatment with rapamycin caused an inhibitory effect on vascular formation, removed ketamine metabolites, decreased the eosinophil-mediated inflammation, and ameliorated bladder hyperactivity, leading to improve bladder function in KIC. Moreover, wortmannin treatment reduced basophil-mediated inflammatory response, improved bladder angiogenesis by increasing capillary density and VEGF expression, to reverse antiangiogenic effect to repair KIC. In conclusion, these findings suggested that autophagy could modulate inflammatory responses and angiogenesis, which improved bladder function in KIC. Full article

(This article belongs to the Special Issue Molecular Diagnosis of Pathologies of the Lower Urinary Tract)

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Review

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18 pages, 1648 KiB

Open AccessReview

Molecular Pathophysiology and Potential Therapeutic Strategies of Ketamine-Related Cystitis

by Chin-Li Chen, Sheng-Tang Wu, Tai-Lung Cha, Guang-Huan Sun and En Meng

Biology 2022, 11(4), 502; https://doi.org/10.3390/biology11040502 - 24 Mar 2022

Cited by 6 | Viewed by 3095

Abstract

Ketamine was first synthesized as a clinical medicine for anesthesia in 1970. It has been used as a recreational drug because of its low cost and hallucination effect in the past decade. Part of ketamine abusers may experience ketamine-related cystitis (KC) and suffer from lower urinary tract symptoms, including urinary frequency, urgency, and severe bladder pain. As the disease progression, a contracted bladder, petechial hemorrhage of the bladder mucosa, and ureteral stricture with hydronephrosis may occur. The pathophysiology of KC is still uncertain, although several hypotheses have been raised. Cessation of ketamine abuse is critical for the management of KC to prevent progressive disease, and effective treatment has not been established. Research has provided some theoretical bases for developing in vitro experiments, animal models, and clinical trials. This review summarized evidence of molecular mechanisms of KC and potential treatment strategies for KC. Further basic and clinical studies will help us better understand the mechanism and develop an effective treatment for KC. Full article

(This article belongs to the Special Issue Molecular Diagnosis of Pathologies of the Lower Urinary Tract)

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