Low-Intensity Extracorporeal Shock Wave Therapy Ameliorates Detrusor Hyperactivity with Impaired Contractility via Transient Potential Vanilloid Channels: A Rat Model for Ovarian Hormone Deficiency.

This study explores low-intensity extracorporeal shock wave therapy (LiESWT)'s efficacy in alleviating detrusor hyperactivity with impaired contractility (DHIC) induced by ovarian hormone deficiency (OHD) in ovariectomized rats. The rats were categorized into the following four groups: sham group; OVX group, subjected to bilateral ovariectomy (OVX) for 12 months to induce OHD; OVX + SW4 group, underwent OHD for 12 months followed by 4 weeks of weekly LiESWT; and OVX + SW8 group, underwent OHD for 12 months followed by 8 weeks of weekly LiESWT. Cystometrogram studies and voiding behavior tracing were used to identify the symptoms of DHIC. Muscle strip contractility was evaluated through electrical-field, carbachol, ATP, and KCl stimulations. Western blot and immunofluorescence analyses were performed to assess the expressions of various markers related to bladder dysfunction. The OVX rats exhibited significant bladder deterioration and overactivity, alleviated by LiESWT. LiESWT modified transient receptor potential vanilloid (TRPV) channel expression, regulating calcium concentration and enhancing bladder capacity. It also elevated endoplasmic reticulum (ER) stress proteins, influencing ER-related Ca2+ channels and receptors to modulate detrusor muscle contractility. OHD after 12 months led to neuronal degeneration and reduced TRPV1 and TRPV4 channel activation. LiESWT demonstrated potential in enhancing angiogenic remodeling, neurogenesis, and receptor response, ameliorating DHIC via TRPV channels and cellular signaling in the OHD-induced DHIC rat model.

Titanium Dioxide (TiO2) Nanoparticle Toxicity in a Caenorhabditis elegans Model.

Titanium dioxide is a compound that is used in the food, cosmetic, and paint industries; however, it is still toxic to humans and the environment. This study determined the toxicities of titanium dioxide nanoparticles (TiO2 NPs) in a Caenorhabditis elegans (C. elegans) model. The effects of commercially available (C-TiO2) and synthetically (S-TiO2) prepared TiO2 NP solutions on lethality, lifespan, growth, reproduction, locomotion, and gene expression were studied in C. elegans. Exposure to TiO2 NPs (0.0, 0.01, 0.1, 1.0, and 10 mg/L) did not result in any change to the survival rate or body length of the nematodes, regardless of the concentration. However, there was a decrease in the reproduction (brood size) and locomotion (body bending and head thrashing) of the nematodes as the TiO2 NP concentration increased. The longevity of the nematodes was shortened following TiO2 NP exposure. The gene expression of sod-1, sod-3, ctl-1, ctl-2, cyp35A2, mlt-1, and mlt-2 in the nematodes showed that there was an overexpression of all genes when the worms were exposed to 1 mg/L C-TiO2 or 10 mg/L S-TiO2. It was therefore concluded that compared with S-TiO2, C-TiO2 possibly causes more toxicity or genotoxicity in the C. elegans model.

The Molecular Mechanism and Therapeutic Application of Autophagy for Urological Disease.

Autophagy is a lysosomal degradation process known as autophagic flux, involving the engulfment of damaged proteins and organelles by double-membrane autophagosomes. It comprises microautophagy, chaperone-mediated autophagy (CMA), and macroautophagy. Macroautophagy consists of three stages: induction, autophagosome formation, and autolysosome formation. Atg8-family proteins are valuable for tracking autophagic structures and have been widely utilized for monitoring autophagy. The conversion of LC3 to its lipidated form, LC3-II, served as an indicator of autophagy. Autophagy is implicated in human pathophysiology, such as neurodegeneration, cancer, and immune disorders. Moreover, autophagy impacts urological diseases, such as interstitial cystitis /bladder pain syndrome (IC/BPS), ketamine-induced ulcerative cystitis (KIC), chemotherapy-induced cystitis (CIC), radiation cystitis (RC), erectile dysfunction (ED), bladder outlet obstruction (BOO), prostate cancer, bladder cancer, renal cancer, testicular cancer, and penile cancer. Autophagy plays a dual role in the management of urologic diseases, and the identification of potential biomarkers associated with autophagy is a crucial step towards a deeper understanding of its role in these diseases. Methods for monitoring autophagy include TEM, Western blot, immunofluorescence, flow cytometry, and genetic tools. Autophagosome and autolysosome structures are discerned via TEM. Western blot, immunofluorescence, northern blot, and RT-PCR assess protein/mRNA levels. Luciferase assay tracks flux; GFP-LC3 transgenic mice aid study. Knockdown methods (miRNA and RNAi) offer insights. This article extensively examines autophagy's molecular mechanism, pharmacological regulation, and therapeutic application involvement in urological diseases.

The effects of using Tempeh as a supplement for type 2 diabetes.

Studies suggest that the consumption of Tempeh can improve abnormal blood glucose and lipid parameters, although it remains still unclear as to whether Tempeh can improve tissue damage. In our study, db/db obese diabetic mice were given Tempeh 1 (300 mg/kg) and Tempeh 2 (600 mg/kg) for 3 months. The tissue samples collected were stained using different tissue-staining methodologies and were compared with the diabetic control group that was not given any Tempeh. Our results demonstrated that consuming high-dose Tempeh for 1 month could significantly reduce serum glucose and body weight in mice whereas the tissue section of our result could validate that consuming high-dose Tempeh for 3 months effectively improves lipid droplet size and lipid accumulation in the liver, aorta, and kidney of the mice. Moreover, an indication of the recovery of the damaged tissue could be observed in the heart and pancreatic tissue when high dosage of Tempeh was given as a treatment. Thus, it can be concluded that continuous consumption of Tempeh as a treatment could improve both blood glucose and body weight of diabetic mice while also improving lipid accumulation and tissue damage.

Urinary levels of organophosphate flame retardants metabolites in a young population from Southern Taiwan and potential health effects.

Background: Organophosphate flame retardants (OPFRs) are widely distributed in the environment and their metabolites are observed in urine, but little is known regarding OPFRs in a broad-spectrum young population from newborns to those aged 18 years. Objectives: Investigate urinary levels of OPFRs and OPFR metabolites in Taiwanese infants, young children, schoolchildren, and adolescents within the general population. Methods: Different age groups of subjects (n=136) were recruited from southern Taiwan to detect 10 OPFR metabolites in urine samples. Associations between urinary OPFRs and their corresponding metabolites and potential health status were also examined. Results: The mean level of urinary Σ10 OPFR in this broad-spectrum young population is 2.25 µg/L (standard deviation (SD) of 1.91 µg/L). Σ10 OPFR metabolites in urine are 3.25 ± 2.84, 3.06 ± 2.21, 1.75 ± 1.10, and 2.32 ± 2.29 µg/L in the age groups comprising of newborns, 1-5 year-olds, 6-10 year-olds, and 11-18 year-olds, respectively, and borderline significant differences were found in the different age groups (p=0.125). The OPFR metabolites of TCEP, BCEP, DPHP, TBEP, DBEP, and BDCPP predominate in urine and comprise more than 90% of the total. TBEP was highly correlated with DBEP in this population (r=0.845, p<0.001). The estimated daily intake (EDI) of Σ5OPFRs (TDCPP, TCEP, TBEP, TNBP, and TPHP) was 2,230, 461, 130, and 184 ng/kg bw/day for newborns, 1-5 yr children, 6-10 yr children, and 11-17 yr adolescents, respectively. The EDI of Σ5OPFRs for newborns was 4.83-17.2 times higher than the other age groups. Urinary OPFR metabolites are significantly correlated with birth length and chest circumference in newborns. Conclusion: To our knowledge, this is the first investigation of urinary OPFR metabolite levels in a broad-spectrum young population. There tended to be higher exposure rates in both newborns and pre-schoolers, though little is known about their exposure levels or factors leading to exposure in the young population. Further studies should clarify the exposure levels and factor relationships.

Effects of Therapeutic Platelet-Rich Plasma on Overactive Bladder via Modulating Hyaluronan Synthesis in Ovariectomized Rat.

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.

Therapeutic Effect of Platelet-Rich Plasma Improves Bladder Overactivity in the Pathogenesis of Ketamine-Induced Ulcerative Cystitis in a Rat Model.

The present study attempted to elucidate whether intravesical instillation of platelet-rich plasma (PRP) could decrease bladder inflammation and ameliorate bladder hyperactivity in ketamine ulcerative cystitis (KIC) rat model. Female Sprague Dawley (S-D) rats were randomly divided into control group, ketamine-treated group, ketamine with PRP treated group, and ketamine with platelet-poor plasma (PPP) treated group. Cystometry and micturition frequency/volume studies were performed to investigate bladder function. The morphological change of bladder was investigated by Mason's trichrome staining. Western blotting analysis were carried out to examine the protein expressions of inflammation, urothelial differentiation, proliferation, urothelial barrier function, angiogenesis and neurogenesis related proteins. The results revealed that treatment with ketamine significantly deteriorated bladder capacity, decreased voiding function and enhanced bladder overactivity. These pathological damage and interstitial fibrosis may via NF-κB/COX-2 signaling pathways and muscarinic receptor overexpression. PRP treatment decreased inflammatory fibrotic biosynthesis, attenuated oxidative stress, promoted urothelial cell regeneration, and enhanced angiogenesis and neurogenesis, thereafter recovered bladder dysfunction and ameliorate the bladder hyperactivity in KIC rat model. These findings suggested that the PRP therapy may offer new treatment options for those clinical KIC patients.

Rapid Control of a SARS-CoV-2 B.1.617.2 (Delta) Variant COVID-19 Community Outbreak: The Successful Experience in Pingtung County of Taiwan.

The Severe Acute Respiratory Syndrome-associated Coronavirus 2 (SARS-CoV-2) was an outbreak in December, 2019 and rapidly spread to the world. All variants of SARS-CoV-2, including the globally and currently dominant Delta variant (Delta-SARS-CoV-2), caused severe disease and mortality. Among all variants, Delta-SARS-CoV-2 had the highest transmissibility, growth rate, and secondary attack rate than other variants except for the new variant of Omicron that still exists with many unknown effects. In Taiwan, the pandemic Delta-SARS-CoV-2 began in Pingtung from 14 June 2021 and ceased at 11 July 2021. Seventeen patients were infected by Delta-SARS-CoV-2 and 1 person died during the Pingtung outbreak. The Public Health Bureau of Pingtung County Government stopped the Delta-SARS-CoV-2 outbreak within 1 month through measures such as epidemic investigation, rapid gene sequencing, rapidly expanding isolation, expanded screening of the Delta-SARS-CoV-2 antigen for people who lived in regional villages, and indirect intervention, including rapid vaccination, short lockdown period, and travel restrictions. Indirect environmental factors, such as low levels of air pollution, tropic weather in the summer season, and rural areas might have accelerated the ability to control the Delta-SARS-CoV-2 spread. This successful experience might be recommended as a successful formula for the unvaccinated or insufficiently vaccinated regions.

The Impact of Background-Level Carboxylated Single-Walled Carbon Nanotubes (SWCNTs-COOH) on Induced Toxicity in Caenorhabditis elegans and Human Cells.

Single-walled carbon nanotubes (SWCNTs) are widely utilized for industrial, biomedical, and environmental purposes. The toxicity of Carboxylated SWCNTs (SWCNTs-COOH) in in vivo models, particularly Caenorhabditis elegans (C. elegans), and in vitro human cells is still unclear. In this study, C. elegans was used to study the effects of SWCNTs-COOH on lethality, lifespan, growth, reproduction, locomotion, reactive oxygen species (ROS) generation, and the antioxidant system. Our data show that exposure to ≥1 µg·L-1 SWCNTs-COOH could induce toxicity in nematodes that affects lifespan, growth, reproduction, and locomotion behavior. Moreover, the exposure of nematodes to SWCNTs-COOH induced ROS generation and the alteration of antioxidant gene expression. SWCNTs-COOH induced nanotoxic effects at low dose of 0.100 or 1.00 µg·L-1, particularly for the expression of antioxidants (SOD-3, CTL-2 and CYP-35A2). Similar nanotoxic effects were found in human cells. A low dose of SWCNTs-COOH induced ROS generation and increased the expression of catalase, MnSOD, CuZnSOD, and SOD-2 mRNA but decreased the expression of GPX-2 and GPX-3 mRNA in human monocytes. These findings reveal that background-level SWCNTs-COOH exerts obvious adverse effects, and C. elegans is a sensitive in vivo model that can be used for the biological evaluation of the toxicity of nanomaterials.

Low Intensity Extracorporeal Shock Wave Therapy as a Novel Treatment for Stress Urinary Incontinence: A Randomized-Controlled Clinical Study.

Background and Objectives: To evaluate the effects of low intensity extracorporeal shock wave therapy (LiESWT) on stress urinary incontinence (SUI). Materials and Methods: This investigation was a multicenter, single-blind, randomized-controlled trial study. Sixty female SUI patients were randomly assigned to receive LiESWT with 0.25 mJ/mm2 intensity, 3000 pulses, and 3 pulses/s, once weekly for a 4-week (W4) and 8-week (W8) period, or an identical sham LiESWT treatment without energy transmission. The primary endpoint was the changes in urine leakage as measured by a pad test and validated standardized questionnaires, while the secondary endpoint was the changes in a 3-day urinary diary among the baseline (W0), the W4 and W8 of LiESWT, and 1-month (F1), 3-month (F3), and 6-month (F6) follow-up after LiESWT. Results: The results showed that 4 weeks of LiESWT could significantly decrease urine leakage based on the pad test and validated standardized questionnaire scores, as compared to the sham group. Moreover, 8 weeks of LiESWT could significantly reduce urine leakage but increase urine volume and attenuate urgency symptoms, which showed meaningful and persistent improvement at W8, F1, F3, and F6. Furthermore, validated standardized questionnaire scores were significantly improved at W8, F1, F3, and F6 as compared to the baseline (W0). Conclusions: Eight weeks of LiESWT attenuated SUI symptoms upon physical activity, reduced urine leakage, and ameliorated overactive bladder symptoms, which implied that LiESWT significantly improved the quality of life. Our findings suggested that LiESWT could serve as a potentially novel and non-invasive treatment for SUI.

Low-Intensity Extracorporeal Shock Wave Therapy Promotes Bladder Regeneration and Improves Overactive Bladder Induced by Ovarian Hormone Deficiency from Rat Animal Model to Human Clinical Trial.

Postmenopausal women with ovary hormone deficiency (OHD) are subject to overactive bladder (OAB) symptoms. The present study attempted to elucidate whether low-intensity extracorporeal shock wave therapy (LiESWT) alters bladder angiogenesis, decreases inflammatory response, and ameliorates bladder hyperactivity to influence bladder function in OHD-induced OAB in human clinical trial and rat model. The ovariectomized (OVX) for 12 months Sprague-Dawley rat model mimicking the physiological condition of menopause was utilized to induce OAB and assess the potential therapeutic mechanism of LiESWT (0.12 mJ/mm2, 300 pulses, and 3 pulses/second). The randomized, single-blinded clinical trial was enrolled 58 participants to investigate the therapeutic efficacy of LiESWT (0.25 mJ/mm2, 3000 pulses, 3 pulses/second) on postmenopausal women with OAB. The results revealed that 8 weeks' LiESWT inhibited interstitial fibrosis, promoted cell proliferation, enhanced angiogenesis protein expression, and elevated the protein phosphorylation of ErK1/2, P38, and Akt, leading to decreased urinary frequency, nocturia, urgency, urgency incontinence, and post-voided residual urine volume, but increased voided urine volume and the maximal flow rate of postmenopausal participants. In conclusion, LiESWT attenuated inflammatory responses, increased angiogenesis, and promoted proliferation and differentiation, thereby improved OAB symptoms, thereafter promoting social activity and the quality of life of postmenopausal participants.

Data on effect of Tempeh Fermentation on patients with type II diabetes.

Type II diabetes (T2D) arises through insulin resistance and a progressive decrease in insulin secretion, which may be partly related to pancreatic beta-cell function decline, obesity, and eventual hyperglycemia [1]. The first line for managing hyperglycemia in patients with T2D includes lifestyle modifications and metformin monotherapy. However, many patients still showed poor glycemic control due to progressive deterioration during the course of T2D [2, 3]. On streptozotocin-induced T2D rats, tempeh fermentation has been shown to be a potentially beneficial dietary supplement for abnormal carbohydrate metabolism [4]. This study was a prospective open-label clinical trial. The data were collected from Kaohsiung Veterans General Hospital Pingtung Branch, Taiwan from August 2018 to July 2019. 35 eligible T2D participants with a mean age of 57.91 ± 10.17 years were enrolled. After taking 2 g tempeh capsules daily for a period of 3 months, the levels of HbA1C and triglyceride were noticeably decreased in the participants. A regression analysis revealed that cholesterol concentration had a significant positive correlation with the concentrations of LDL, but triglyceride concentration had a significant negative correlation with the concentrations of HDL in the pre- and the post-tempeh treatment.

Low Intensity Extracorporeal Shock Wave Therapy as a Potential Treatment for Overactive Bladder Syndrome.

BACKGROUND: The present study attempted to investigate the therapeutic effect and duration of low intensity extracorporeal shock wave therapy (LiESWT) on overactive bladder (OAB) symptoms, including social activity and the quality of life (QoL). METHODS: In this prospective, randomized, single-blinded clinical trial, 65 participants with OAB symptom were randomly divided into receive LiESWT (0.25 mJ/mm2, 3000 pulses, 3 pulses/second) once a week for 8 weeks, or an identical sham LiESWT treatment without the energy transmission. We analyzed the difference in overactive bladder symptom score (OABSS) and 3-day urinary diary as the primary end. The secondary endpoint consisted of the change in uroflowmetry, post-voided residual (PVR) urine, and validated standardized questionnaires at the baseline (W0), 4-week (W4) and 8-week (W8) of LiESWT, and 1-month (F1), 3-month (F3) and 6-month (F6) follow-up after LiESWT. RESULTS: 8-week LiESWT could significantly decrease urinary frequency, nocturia, urgency, and PVR volume, but meaningfully increase functional bladder capacity, average voided volume and maximal flow rate (Qmax) as compared with the W0 in the LiESWT group. In addition, the scores calculated from questionnaires were meaningfully reduced at W4, W8, F1, F3, and F6 in the LiESWT group. CONCLUSIONS: Our results revealed that the therapeutic efficacy of LiESWT could improve voided volume and ameliorate OAB symptoms, such as urgency, frequency, nocturia, and urinary incontinence, and lasted up to 6 month of follow-up. Moreover, LiESWT treatment brought statistically significant and clinically meaningful improvements in social activity and QoL of patients. These findings suggested that LiESWT could serve as an alternative non-invasive therapy for OAB patients.

Bladder Hyperactivity Induced by Oxidative Stress and Bladder Ischemia: A Review of Treatment Strategies with Antioxidants.

Overactive bladder (OAB) syndrome, including frequency, urgency, nocturia and urgency incontinence, has a significantly negative impact on the quality-of-life scale (QoL) and can cause sufferer withdrawal from social activities. The occurrence of OAB can result from an imbalance between the production of pro-oxidants, such as free radicals and reactive species, and their elimination through protective mechanisms of antioxidant-induced oxidative stress. Several animal models, such as bladder ischemia/reperfusion (I/R), partial bladder outlet obstruction (PBOO) and ovarian hormone deficiency (OHD), have suggested that cyclic I/R during the micturition cycle induces oxidative stress, leading to bladder denervation, bladder afferent pathway sensitization and overexpression of bladder-damaging molecules, and finally resulting in bladder hyperactivity. Based on the results of previous animal experiments, the present review specifically focuses on four issues: (1) oxidative stress and antioxidant defense system; (2) oxidative stress in OAB and biomarkers of OAB; (3) OAB animal model; (4) potential nature/plant antioxidant treatment strategies for urinary dysfunction with OAB. Moreover, we organized the relationships between urinary dysfunction and oxidative stress biomarkers in urine, blood and bladder tissue. Reviewed information also revealed the summary of research findings for the effects of various antioxidants for treatment strategies for OAB.

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

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.

Anti-Inflammatory Effects Induced by Near-Infrared Light Irradiation through M2 Macrophage Polarization.

Near-infrared (NIR) can penetrate the dermis. NIR is able to regulate cutaneous component cells and immune cells and shows significant anti-inflammatory therapeutic effects. However, the mechanisms of these effects are largely unknown. The purpose of this study is to elucidate NIR-induced molecular mechanisms on macrophages because macrophages play initial roles in directing immune responses by their M1 or M2 polarizations. Proteomic analysis revealed that NIR radiation enhanced the expression of mitochondrial respiratory gene citrate synthase. This increased citrate synthase expression was triggered by NIR-induced H3K4 hypermethylation on the citrate synthase gene promoter but not by heat, which led to macrophage M2 polarization and finally resulted in TGFß1 release from CD4+ cells. These cellular effects were validated in human primary macrophages and abdominal NIR-irradiated mouse experiments. In a phorbol 12-myristate 13-acetate‒induced inflammatory model on mouse ear, we confirmed that NIR irradiation induced significant anti-inflammatory effects through decreased M1 counts, reduced TNF-α, and increased CCL22 and/or TGFß1 levels.

Urinary Biomarkers in Interstitial Cystitis/Bladder Pain Syndrome and Its Impact on Therapeutic Outcome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is defined as a chronic bladder disorder with suprapubic pain (pelvic pain) and pressure and/or discomfort related to bladder filling accompanied by lower urinary tract symptoms, such as urinary frequency and urgency without urinary tract infection (UTI) lasting for at least 6 weeks. IC/BPS presents significant bladder pain and frequency urgency symptoms with unknown etiology, and it is without a widely accepted standard in diagnosis. Patients' pathological features through cystoscopy and histologic features of bladder biopsy determine the presence or absence of Hunner lesions. IC/PBS is categorized into Hunner (ulcerative) type IC/BPS (HIC/BPS) or non-Hunner (nonulcerative) type IC/BPS (NHIC/BPS). The pathophysiology of IC/BPS is composed of multiple possible factors, such as chronic inflammation, autoimmune disorders, neurogenic hyperactivity, urothelial defects, abnormal angiogenesis, oxidative stress, and exogenous urine substances, which play a crucial role in the pathophysiology of IC/BPS. Abnormal expressions of several urine and serum specimens, including growth factor, methylhistamine, glycoprotein, chemokine and cytokines, might be useful as biomarkers for IC/BPS diagnosis. Further studies to identify the key molecules in IC/BPS will help to improve the efficacy of treatment and identify biomarkers of the disease. In this review, we discuss the potential medical therapy and assessment of therapeutic outcome with urinary biomarkers for IC/BPS.

Low-Intensity Extracorporeal Shock Wave Therapy Ameliorates the Overactive Bladder: A Prospective Pilot Study.

OBJECTIVE: In the present clinical trial, we evaluated the therapeutic effects of low-intensity extracorporeal shockwave therapy (LiESWT) on overactive bladder (OAB). METHODS: Female subjects with ages of 20-75 years and who have been clinically diagnosed with OAB were included in the study. The LiESWT (DUOLITH SD1 T-TOP, AG) applicator was placed on the suprapubic skin area and applied with an intensity of 0.25 mJ/mm2, 3000 pulses, and 3 pulses/second. To assess the therapeutic efficacy, all subjects were required to complete the validated OAB symptoms and life bothersome questionnaires, 3-day urinary diary, uroflowmetry, and post-voided residual urine (PVR) measurement at 4 weeks of LiESWT (W4), 8 weeks of LiESWT (W8), 1-month follow-up (F1), and 3-month follow-up (F3) after LiESWT. RESULT: 82 subjects with the mean age of 56.5 ± 1.2 years were enrolled. The questionnaire scores were significantly improved at W4, W8, F1, and F3 as compared to baseline data (W0). At W8, the mean values of functional bladder capacity were meaningfully increased. According to the 3-day urinary diary, daytime frequency, urgency, and nocturia were significantly decreased. The uroflowmetry results showed that the mean voided urine volume and the maximal flow rate (Q max) were noticeably increased. PVR volume was also significantly decreased. CONCLUSIONS: The data demonstrated that 8-week LiESWT ameliorated the OAB symptoms, promoted the uroflow parameters, and improved the quality of life (QoL) in OAB patients, suggesting that LiESWT might serve as an alternative noninvasive therapy for OAB.

Therapeutic effects of Low intensity extracorporeal low energy shock wave therapy (LiESWT) on stress urinary incontinence.

This study aimed to evaluate the therapeutic effects of Low intensity extracorporeal low energy shock wave therapy (LiESWT) on stress urinary incontinence (SUI). The investigation was a single-arm, open-label, multicentre study conducted in Taiwan. 50 female patients with SUI received LiESWT-treated with 0.25 mJ/mm2 intensity, 3000 pulses, and 3 pulses/second, once weekly for 4-weeks (W4) and 8-weeks (W8). The pad test, uroflowmetry, life quality questionnaires, and 3-day urinary diary measurement were performed before and after LiESWT intervention. The results revealed that 8-week of LiESWT treatment meaningfully improved urine leakage (pad test), maximum flow rate, post-voided residual urine, average urine volume, functional bladder capacity, urinary frequency, urgency symptom, and nocturia, which also persisted to show significant improvements at 1-month follow up (F1). Moreover, bothersome questionnaires scores were significantly improved at W4, W8, and F1 as compared to the baseline (W0). These results indicated that 8 weeks of LiESWT attenuated SUI symptoms on physical activity, reduced bladder leaks and overactive bladder (OAB), implying that LiESWT brought significant improvement in the quality of life. (ClinicalTrials.gov number, NCT04059133).

Nociceptive transient receptor potential canonical 7 (TRPC7) mediates aging-associated tumorigenesis induced by ultraviolet B.

Aging, cancer, and longevity have been linked to intracellular Ca2+ signaling and nociceptive transient receptor potential (TRP) channels. We found that TRP canonical 7 (TRPC7) is a nociceptive mechanoreceptor and that TRPC7 channels specifically mediate the initiation of ultraviolet B (UVB)-induced skin aging and tumor development due to p53 gene family mutations. Within 30 min after UVB irradiation, TRPC7 mediated UVB-induced Ca2+ influx and the subsequent production of reactive oxygen species in skin cells. Notably, this function was unique to TRPC7 and was not observed for other TRP channels. In TRPC7 knockout mice, we did not observe the significant UVB-associated pathology seen in wild-type mice, including epidermal thickening, abnormal keratinocyte differentiation, and DNA damage response activation. TRPC7 knockout mice also had significantly fewer UVB-induced cancerous tumors than did wild-type mice, and UVB-induced p53 gene family mutations were prevented in TRPC7 knockout mice. These results indicate that TRPC7 activity is pivotal in the initiation of UVB-induced skin aging and tumorigenesis and that the reduction in TRPC7 activity suppresses the UVB-induced aging process and tumor development. Our findings support that TRPC7 is a potential tumor initiator gene and that it causes cell aging and genomic instability, followed by a change in the activity of proto-oncogenes and tumor suppressor genes to promote tumorigenesis.