Proteome changes in human bladder T24 cells induced by hydroquinone derived from Arctostaphylos uva-ursi herbal preparation.

ETHNOPHARMACOLOGICAL RELEVANCE: Arctostaphylos uva-ursi (L.) Spreng. (bearberry) is a well-known traditional herbal plant used as a urinary tract disinfectant. Its antiseptic and diuretic properties can be attributed to hydroquinone, obtained by hydrolysis of arbutin. AIM OF THE STUDY: This study aimed to determine the toxic profile of free hydroquinone on urinary bladder cells (T24) as a target of therapeutic action. MATERIALS AND METHODS: Quantitative and qualitative analysis of the extract and the digestive stability and bioavailability of arbutin and hydroquinone were performed by HPLC assay and simulated in vitro digestion, respectively. Cytotoxic effect, reactive oxygen species induction and proteome changes in T24 cells after hydroquinone treatment were determined using Neutral red assay, 2',7'-dichlorofluorescein-diacetate (DCFH-DA) assay and mass spectrometry, respectively. RESULTS: Through in vitro digestion, arbutin was stable, but hydroquinone increased after pepsin treatment (109.6%) and then decreased after the small intestine phase (65.38%). The recommended doses of Uva-ursi had a cytotoxic effect on T24 cells only when all hydroquinone conjugates were converted to free hydroquinone (320 and 900 µg/mL) and the toxic effect was enhanced by recovery. One cup of the therapeutic dose had a prooxidative effect after 4 h of incubation. Shorter time of cell exposure (2 h) to hydroquinone did not have any impact on reactive oxygen species induction. Proteomic analysis found 17 significantly up-regulated proteins compared to control. Hydroquinone activated proteins related to oxidative stress response, stress-adaptive signalling, heat shock response and initiation of translation. CONCLUSIONS: Despite the therapeutic properties of bearberry, up-regulated T24 cell proteins are evidence that plant compounds, although from a natural source, may exhibit negative properties.

The role of caspase-1, caspase-4 and NLRP3 in regulating the host cell response evoked by uropathogenic Escherichia coli.

The inflammasome-associated proteins caspase-1, caspase-4 and NLRP3 have been emphasised to be essential in the host cell response during urinary tract infection (UTI) by regulating IL-1ß release. Our aim was to investigate how the inflammasome-associated proteins regulate the cell response of bladder epithelial cells during infection with uropathogenic Escherichia coli (UPEC). Human bladder epithelial cells (5637) and CRISPR/Cas9 generated caspase-1, caspase-4 and NLRP3 knockdown cells were stimulated with the UPEC strain CFT073. Using Olink proteomics and real time RT-PCR, we showed that caspase-1, caspase-4 and NLRP3 are vital for the expression of many inflammatory genes and proteins from bladder epithelial cells. When investigating the effect of inflammasome-associated proteins on neutrophils, we found that conditioned medium from UPEC-infected caspase-4 knockdown cells significantly increased phagocytosis of CFT073 and significantly decreased ROS production from neutrophils. In contrast, conditioned medium from UPEC-infected NLRP3 knockdown cells significantly decreased the phagocytosis of CFT073 and significantly increased the ROS production from neutrophils. In conclusion, we showed that the inflammasome-associated proteins contribute to the host cell response during UPEC infection.

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.

Single-cell RNA sequencing reveals the epithelial cell heterogeneity and invasive subpopulation in human bladder cancer.

Bladder cancer represents a highly heterogeneous disease characterized by distinct histological, molecular and clinical phenotypes, and a detailed analysis of tumor cell invasion and crosstalks within bladder tumor cells has not been determined. Here, we applied droplet-based single-cell RNA sequencing (scRNA-seq) to acquire transcriptional profiles of 36 619 single cells isolated from seven patients. Single cell transcriptional profiles matched well with the pathological basal/luminal subtypes. Notably, in T1 tumors diagnosed as luminal subtype, basal cells displayed characteristics of epithelial-mesenchymal transition (EMT) and mainly located at the tumor-stromal interface as well as micrometastases in the lamina propria. In one T3 tumor, muscle-invasive tumor showed significantly higher expression of cancer stem cell markers SOX9 and SOX2 than the primary tumor. We additionally analyzed communications between tumor cells and demonstrated its relevance to basal/luminal phenotypes. Overall, our single-cell study provides a deeper insight into the tumor cell heterogeneity associated with bladder cancer progression.

Human Bronchial Epithelial Cell Growth on Homologous Versus Heterologous Tissue Extracellular Matrix.

BACKGROUND: Extracellular matrix (ECM) bioscaffolds produced by decellularization of source tissue have been effectively used for numerous clinical applications. However, decellularized tracheal constructs have been unsuccessful due to the immediate requirement of a functional airway epithelium on surgical implantation. ECM can be solubilized to form hydrogels that have been shown to support growth of many different cell types. The purpose of the present study is to compare the ability of airway epithelial cells to attach, form a confluent monolayer, and differentiate on homologous (trachea) and heterologous (urinary bladder) ECM substrates for potential application in full tracheal replacement. MATERIALS AND METHODS: Porcine tracheas and urinary bladders were decellularized. Human bronchial epithelial cells (HBECs) were cultured under differentiation conditions on acellular tracheal ECM and urinary bladder matrix (UBM) bioscaffolds and hydrogels and were assessed by histology and immunolabeling for markers of ciliation, goblet cell formation, and basement membrane deposition. RESULTS: Both trachea and urinary bladder tissues were successfully decellularized. HBEC formed a confluent layer on both trachea and UBM scaffolds and on hydrogels created from these bioscaffolds. Cells grown on tracheal and UBM hydrogels, but not on bioscaffolds, showed positive-acetylated tubulin staining and the presence of mucus-producing goblet cells. Collagen IV immunolabeling showed basement membrane deposition by these cells on the surface of the hydrogels. CONCLUSIONS: ECM hydrogels supported growth and differentiation of HBEC better than decellularized ECM bioscaffolds and show potential utility as substrates for promotion of a mature respiratory epithelium for regenerative medicine applications in the trachea.

Single-cell transcriptomes of mouse bladder urothelium uncover novel cell type markers and urothelial differentiation characteristics.

OBJECTIVES: Much of the information to date in terms of subtypes and function of bladder urothelial cells were derived from anatomical location or by the expression of a small number of marker genes. To have a comprehensive map of the cellular anatomy of bladder urothelial cells, we performed single-cell RNA sequencing to thoroughly characterize mouse bladder urothelium. MATERIALS AND METHODS: A total of 18,917 single cells from mouse bladder urothelium were analysed by unbiased single-cell RNA sequencing. The expression of the novel cell marker was confirmed by immunofluorescence using urinary tract infection models. RESULTS: Unsupervised clustering analysis identified 8 transcriptionally distinct cell subpopulations from mouse bladder urothelial cells. We discovered a novel type of bladder urothelial cells marked by Plxna4 that may be involved with host response and wound healing. We also found a group of basal-like cells labelled by ASPM that could be the progenitor cells of adult bladder urothelium. ASPM+ urothelial cells are significantly increased after injury by UPEC. In addition, specific transcription factors were found to be associated with urothelial cell differentiation. At the last, a number of interstitial cystitis/bladder pain syndrome-regulating genes were found differentially expressed among different urothelial cell subpopulations. CONCLUSIONS: Our study provides a comprehensive characterization of bladder urothelial cells, which is fundamental to understanding the biology of bladder urothelium and associated bladder disease.

HER2 overexpression triggers the IL-8 to promote arsenic-induced EMT and stem cell-like phenotypes in human bladder epithelial cells.

Arsenic is a natural chemical element that is strongly associated with bladder cancer. Understanding the underlying mechanisms behind the association between arsenic and bladder cancer as well as identifying effective preventive interventions will help reduce the incidence and mortality of this disease. The epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties play key roles in cancer development and progression. Here, we reported that chronic exposure to arsenic resulted in EMT and increased levels of the CSC marker CD44 in human uroepithelial cells. Furthermore, IL-8 promoted a mesenchymal phenotype and upregulated CD44 by activating the ERK, AKT and STAT3 signaling. Phosphorylation of the human epidermal growth factor receptor 2 (HER2) was key for arsenic-induced IL-8 overexpression and depended on the simultaneous activation of the MAPK, JNK, PI3K/AKT and GSK3ß signaling pathways. We also found that genistein inhibited arsenic-induced HER2 phosphorylation and downregulated its downstream signaling pathways, thereby inhibiting progression of EMT, and reducing CD44 expression levels. These results demonstrate that the HER2/IL-8 axis is related to the acquisition of an EMT phenotype and CSCs in arsenic-treated cells. The inhibitory effects of genistein on EMT and CSCs provide a new perspective for the intervention and potential chemotherapy against arsenic-induced bladder cancer.

Bladder Tumor Subtype Commitment Occurs in Carcinoma In Situ Driven by Key Signaling Pathways Including ECM Remodeling.

Basal and luminal subtypes of invasive bladder tumors have significant prognostic and predictive impacts for patients. However, it remains unclear whether tumor subtype commitment occurs in noninvasive urothelial lesions or in carcinoma in situ (CIS) and which gene pathways are important for bladder tumor progression. To understand the timing of this commitment, we used gene expression and protein analysis to create a global overview of 36 separate tissues excised from a whole bladder encompassing urothelium, noninvasive urothelial lesions, CIS, and invasive carcinomas. Additionally investigated were matched CIS, noninvasive urothelial lesions, and muscle-invasive bladder cancers (MIBC) from 22 patients. The final stage of subtype commitment to either a luminal or basal MIBC occurred at the CIS transition. For all tissues combined, hierarchical clustering of subtype gene expression revealed three subtypes: "luminal," "basal," and a "luminal p53-/extracellular matrix (ECM)-like" phenotype of ECM-related genes enriched in tumor-associated urothelium, noninvasive urothelial lesions, and CIS, but rarely invasive, carcinomas. A separate cohort of normal urothelium from noncancer patients showed significantly lower expression of ECM-related genes compared with tumor-associated urothelium, noninvasive urothelial lesions, and CIS. A PanCancer Progression Panel of 681 genes unveiled pathways specific for the luminal p53-/ECM-like cluster, for example, ECM remodeling, angiogenesis, epithelial-to-mesenchymal transition, cellular discohesion, cell motility involved in tumor progression, and cell proliferation and oncogenic ERBB2/ERBB3 signaling for invasive carcinomas. In conclusion, this study provides insights into bladder cancer subtype commitment and associated signaling pathways, which could help predict therapy response and enhance our understanding of therapy resistance. SIGNIFICANCE: This study demonstrates that CIS is the stage of commitment for determining MIBC tumor subtype, which is relevant for patient prognosis and therapy response.

Creation of bladder assembloids mimicking tissue regeneration and cancer.

Current organoid models are limited by their inability to mimic mature organ architecture and associated tissue microenvironments1,2. Here we create multilayer bladder 'assembloids' by reconstituting tissue stem cells with stromal components to represent an organized architecture with an epithelium surrounding stroma and an outer muscle layer. These assembloids exhibit characteristics of mature adult bladders in cell composition and gene expression at the single-cell transcriptome level, and recapitulate in vivo tissue dynamics of regenerative responses to injury. We also develop malignant counterpart tumour assembloids to recapitulate the in vivo pathophysiological features of urothelial carcinoma. Using the genetically manipulated tumour-assembloid platform, we identify tumoural FOXA1, induced by stromal bone morphogenetic protein (BMP), as a master pioneer factor that drives enhancer reprogramming for the determination of tumour phenotype, suggesting the importance of the FOXA1-BMP-hedgehog signalling feedback axis between tumour and stroma in the control of tumour plasticity.

Protective effect of Aster tataricus extract on NLRP3-mediated pyroptosis of bladder urothelial cells.

Aster tataricus L.f. is a traditional Eastern Asian herbal medicine used for the relief of uroschesis-related illnesses and has been demonstrated clinically to exert satisfied effects. However, the mechanism of its therapeutic action remains unclear. The present study aimed to evaluate the protective mechanism of Aster tataricus extract (ATE) on CYP or LPS + ATP-induced interstitial cystitis (IC), we successfully constructed the induced IC Sprague-Dawley (SD) rat model and IC human urothelium cell (SV-HUC-1) model. The main compounds of ATE were determined by LC-MS. After intervention, the changes on the bladder wall morphology and inflammation were observed in each group. SV-HUC1 cell viability was measured by MTT and double stained with Hoechst 33342 and propidium iodide (PI). The expression levels of NLRP3, Pro-caspase-1, Caspsae-1 p20, GSDMD, GSDMD-N and Cleave-IL-1ß in vivo and in vitro in different groups were detected by Western blotting. ATE significantly alleviated oedema and haemorrhage and reduced the inflammation index and histopathological score in SD rat bladder. The results of cell revealed that ATE could improve cell viability and decrease pyroptosis ratio. The expression of NLRP3 and other pyroptosis-related protein was remarkably decreased by ATE both in vivo and in vitro. ATE may be used as an inhibitor of NLRP3 in treating IC. The discovery of NLRP3/Caspase-1/GSDMD-N as a new protective pathway provides a new direction for protecting cell against IC.

Bladder reconstruction using autologous smooth muscle cell sheets grafted on a pre-vascularized capsule.

Rationale: Construction of functional vascularized three-dimensional tissues has been a longstanding objective in the field of tissue engineering. The efficacy of using a tissue expander capsule as an induced vascular bed to prefabricate functional vascularized smooth muscle tissue flaps for bladder reconstruction in a rabbit model was tested. Methods: Skin tissue expanders were inserted into the groin to induce vascularized capsule pouch formation. Smooth muscle cells and endothelial progenitor cells were harvested and cocultured to form pre-vascularized smooth muscle cell sheet. Then repeated transplantation of triple-layer cell sheet grafts onto the vascularized capsular tissue was performed at 2-day intervals to prefabricate functional vascularized smooth muscle tissue flaps. Bladder muscular wall defects were created and repaired by six-layer cell sheet graft (sheet only), capsule flap (capsule only) and vascularized capsule prelaminated with smooth muscle cell sheet (sheet plus capsule). The animals were followed for 3 months after implantation and their bladders were explanted serially. Results: Bladder capacity and compliance were maintained in sheet plus capsule group throughout the 3 months. Tissue bath stimulation demonstrated that contractile responses to carbachol and KCl among the three groups revealed a significant difference (p < 0.05). Histologically, inflammation was evident in the capsule only group at 1 month and fibrosis was observed in sheet only group at 3 months. The vessel density in capsule only and sheet plus capsule group were significantly higher than in the sheet only group at each time point (p < 0.05). Comparison of the smooth muscle content among the three groups revealed a significant difference (p < 0.05). Conclusion: These results proved that the capsule may serve as an induced vascular bed for vascularized smooth muscle tissue flap prefabrication. The prefabricated functional vascularized smooth muscle tissue flap has the potential for reliable bladder reconstruction and may create new opportunities for vascularization in 3-D tissue engineering.

Single-cell analysis uncovers fibroblast heterogeneity and criteria for fibroblast and mural cell identification and discrimination.

Many important cell types in adult vertebrates have a mesenchymal origin, including fibroblasts and vascular mural cells. Although their biological importance is undisputed, the level of mesenchymal cell heterogeneity within and between organs, while appreciated, has not been analyzed in detail. Here, we compare single-cell transcriptional profiles of fibroblasts and vascular mural cells across four murine muscular organs: heart, skeletal muscle, intestine and bladder. We reveal gene expression signatures that demarcate fibroblasts from mural cells and provide molecular signatures for cell subtype identification. We observe striking inter- and intra-organ heterogeneity amongst the fibroblasts, primarily reflecting differences in the expression of extracellular matrix components. Fibroblast subtypes localize to discrete anatomical positions offering novel predictions about physiological function(s) and regulatory signaling circuits. Our data shed new light on the diversity of poorly defined classes of cells and provide a foundation for improved understanding of their roles in physiological and pathological processes.

Sangiangols A and B, Two New Dolabellanes from an Indonesian Marine Soft Coral, Anthelia sp.

A new, rare trinor-dolabellane diterpenoid, sangiangol A (1), and one new dolabellane diterpenoid, sangiangol B (2), together with known cembranes and dolabellanes (3-8), were isolated from the ethyl acetate layer of an extract of an Indonesian marine soft coral, Anthelia sp. Compounds 1-8 exhibited moderate cytotoxicity against an NBT-T2 cell line (0.5-10 µg/mL). The structures of the new compounds were determined by analyzing their spectra and a molecular modelling study. A possible biosynthetic pathway for sangiangols A (1) and B (2) is presented. Cytotoxicity requires two epoxide rings or a chlorine atom, as in 4 (stolonidiol) and 5 (clavinflol B).

Neonatal Bladder-derived Mesenchymal Stem Cells Ameliorate Bladder Dysfunction in Diabetic Rat Models.

PURPOSE: To evaluate the effect of a new mesenchymal stem cell type derived from the neonatal bladder (nMSC-B) on diabetic bladder dysfunction (DBD). MATERIALS AND METHODS: nMSC-B were harvested from neonatal male Sprague-Dawley rat's bladder and expanded in culture. nMSC-B were transferred to Type-1 diabetic rats which were induced by a single dose 45 mg/kg Streptozocin (STZ). Stem cells were transferred via intraperitoneally (IP) (DM-IP group, n:6) and by direct injection to the detrusor (DM-D group, n:6) at 12th week following diabetes and compared with Phosphate Buffered Saline (PBS) injected diabetic rats (DM-PBS group, n:6) and age-matched PBS injected non-diabetic normal rats (NR-PBS group, n:6). All rats were evaluated histopathologically and functionally four weeks after the stem cell treatment. RESULTS: nMSC-B showed improvement in both voiding function and bladder structure. The maximum voiding pressure (MVP) values in the DM-PBS group were lower compare to DM-IP, DM-D and NR-PBS groups (13.27 ± 0.78 vs 16.27 ± 0.61, 28.59 ± 2.09, 21.54 ± 1.00, respectively, P < .001). There was a significant improvement for MVP values in stem cell-treated groups. Immunohistochemical examination revealed decreased bladder smooth muscle (SM), increased fibrosis and desquamation in urothelia in diabetic groups compared to normal group(P < .001). We detected recovery in the stem cell groups. This recovery was more evident in DM-D group.  No statistical difference was observed in SM and fibrosis between DM-D and NR-PBS groups (P = .9). CONCLUSION: It was shown that nMSCBs provided amelioration of DBD. We think that nMSC-B constitutes an effective treatment method in DBD.

D2-40/podoplanin expression in cancer stroma by immunohistochemical staining is associated with poor prognosis in bladder cancer patients after radical cystectomy.

OBJECTIVES: We assessed whether D2-40/podoplanin (PDPN) could be used to identify bladder cancer patients with a higher probability of benefiting from cisplatin-based combination chemotherapy. PATIENTS AND METHODS: We investigated PDPN expression by immunohistochemical analysis of cystectomy specimens from 96 bladder cancer patients who had undergone radical cystectomy without neoadjuvant or adjuvant cisplatin-based combination chemotherapy until recurrence. We classified the cases into 2 groups according to the achievement of 2-year recurrence-free survival (RFS) and evaluated whether PDPN expression was associated with patient prognosis. We also classified the 96 cases into 3 groups according to the possible need for perioperative chemotherapy based on the response to chemotherapy after recurrence as "unnecessary" (achieving 2-year RFS), "responder" (recurring within 2 years and responding to chemotherapy after recurrence), and "non-responder" (not responding chemotherapy following recurrence) and compared PDPN expression between these groups. RESULTS: Among 13 cases diagnosed with clinically

The Serine Protease Autotransporters TagB, TagC, and Sha from Extraintestinal Pathogenic Escherichia coli Are Internalized by Human Bladder Epithelial Cells and Cause Actin Cytoskeletal Disruption.

TagB, TagC (tandem autotransporter genes B and C), and Sha (Serine-protease hemagglutinin autotransporter) are recently described members of the SPATE (serine protease autotransporters of Enterobacteriaceae) family. These SPATEs can cause cytopathic effects on bladder cells and contribute to urinary tract infection in a mouse model. Bladder epithelial cells form an important barrier in the urinary tract. Some SPATEs produced by pathogenic E. coli are known to breach the bladder epithelium. The capacity of these newly described SPATEs to alter bladder epithelial cells and the role of the serine protease active site were investigated. All three SPATE proteins were internalized by bladder epithelial cells and altered the distribution of actin cytoskeleton. Sha and TagC were also shown to degrade mucin and gelatin respectively. Inactivation of the serine catalytic site in each of these SPATEs did not affect secretion of the SPATEs from bacterial cells, but abrogated entry into epithelial cells, cytotoxicity, and proteolytic activity. Thus, our results show that the serine catalytic triad of these proteins is required for internalization in host cells, actin disruption, and degradation of host substrates such as mucin and gelatin.

Enhancement of transduction efficiency using Adeno-associated viral vectors by chemical pretreatment to mice bladder urothelium.

Adeno-associated virus (AAV) vectors have been recognized as promising tools for gene delivery. The bladder is a seemingly ideal organ for virus transfer, with easy access through the urethra enabling organ-specific delivery. However, achieving adequate transduction efficiency in the urothelium has been a major challenge because of the barrier function of the glycosaminoglycan (GAG) layer. We investigated optimal pretreatments of the bladder urothelium to maximize transduction efficiency by AAV vectors in vivo. Murine bladders were pretreated with five different chemical agents followed by transurethral instillation with an AAV2 vector encoding a tdTOMATO reporter. After 7 days, transduction efficiency of the urothelium was evaluated. Bladder urothelia pretreated with HCl showed clear evidence of AAV infection and gene delivery. Mice treated with 0.1 N HCl for 4 min showed significantly higher survival rates (nearly 80 %) compared with mice receiving other pretreatment regimens. AAV vector transduction in the urothelium was observed in seven of 20 mice (35 %), and the mean transduction efficiency in these mice was 14.5 %. Thus, HCl pretreatment enhanced transduction efficiency of the mice bladder urothelium by an AAV vector in vivo. Pretreatment with 0.1 N HCl for 4 min was the optimal condition to maximize survival and transduction efficiency of the urothelium.

Urinary Bladder Matrix Scaffolds Promote Pericardium Repair in a Porcine Model.

Pericardium closure after cardiac surgery is recommended to prevent postoperative adhesions to the sternum. Synthetic materials have been used as substitutes, with limited results because of impaired remodeling and fibrotic tissue formation. Urinary bladder matrix (UBM) scaffolds promote constructive remodeling that more closely resemble the native tissue. The aim of the study is to evaluate the host response to UBM scaffolds in a porcine model of partial pericardial resection. Twelve Landrace pigs were subjected to a median sternotomy. A 5 × 7 cm pericardial defect was created and then closed with a 5 × 7 cm multilayer UBM patch (UBM group) or left as an open defect (control group). Animals were survived for 8 wk. End points included gross morphology, biomechanical testing, histology with semiquantitative score, and cardiac function. The UBM group showed mild adhesions, whereas the control group showed fibrosis at the repair site, with robust adhesions and injury to the coronary bed. Load at failure (gr) and stiffness (gr/mm) were lower in the UBM group compared with the native pericardium (199.9 ± 59.2 versus 405.3 ± 99.89 g, P = 0.0536 and 44.23 ± 15.01 versus 146.5 ± 24.38 g/mm, P = 0.0025, respectively). In the UBM group, the histology resembled native pericardial tissue, with neovascularization, neofibroblasts, and little inflammatory signs. In contrast, control group showed fibrotic tissue with mononuclear infiltrates and a lack of organized collagen fibers validated with a histologic score. Both groups had normal ultrasonography results without cardiac motility disorders. In this setting, UBM scaffolds showed appropriate features for pericardial repair, restoring tissue properties that could help reduce postsurgical adhesions and prevent its associated complications.

Experimental study of the difference in deformation between normal and pathological, renal and bladder, cells induced by acoustic radiation force.

Previous studies have shown that alterations in the mechanical properties of cells may be associated with the onset and progression of some forms of pathology. In this paper, an experimental study of two types of cells, renal (cancer) and bladder (cancer) cells, is described which used acoustic radiation force (ARF) generated by a high-frequency ultrasound focusing transducer and performed on the operating platform of an inverted light microscope. Comparing images of cancer cells with those of normal cells of the same kind, we find that the cancer cells are more prone to deform than normal cells of the same kind under the same ARF. In addition, cancer cells with higher malignancy are more deformable than those with lower malignancy. This means that the deformability of cells may be used to distinguish diseased cells from normal ones, and more aggressive cells from less aggressive ones, which may provide a more rapid and accurate method for clinical diagnosis of urological disease in the future.