Comparison of bladder carcinogenesis biomarkers in the urine of traditional cigarette users and e-cigarette users.

Background: During the use of electronic cigarettes (e-cigarettes), users are still exposed to carcinogens similar to those found in tobacco products. Since these carcinogens are metabolized and excreted in urine, they may have carcinogenic effects on the bladder urinary tract epithelium. This meta-analysis aimed to compare bladder cancer carcinogens in the urine of tobacco users and e-cigarette users using a large number of samples. Methods: A systematic meta-analysis was performed using data obtained from several scientific databases (up to November 2023). This cumulative analysis was performed following the Preferred Reporting Items for Systematic Evaluation and Meta-Analysis (PRISMA) and Assessing the Methodological Quality of Systematic Evaluations (AMSTAR) guidelines, according to a protocol registered with PROSPERO. This study was registered on PROSPERO and obtained the unique number: CRD42023455600. Results: The analysis included 10 high-quality studies that considered polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs) and tobacco-specific nitrosamines (TSNAs). Statistical indicators show that there is a difference between the tobacco user group and the e-cigarette user group in terms of 1-Hydroxynaphthalene (1-NAP) [weighted mean difference (WMD)10.14, 95% confidence interval (CI) (8.41 to 11.88), p < 0.05], 1-Hydroxyphenanthrene (1-PHE) [WMD 0.08, 95% CI (-0.14 to 0.31), p > 0.05], 1-Hydroxypyrene (1-PYR) [WMD 0.16, 95% CI (0.12 to 0.20), p < 0.05], 2-Hydroxyfluorene (2-FLU) [WMD 0.69, 95% CI (0.58 to 0.80), p < 0.05], 2-Hydroxynaphthalene (2-NAP) [WMD 7.48, 95% CI (4.15 to 10.80), p < 0.05], 3-Hydroxyfluorene (3-FLU) [WMD 0.57, 95% CI (0.48 to 0.66), p < 0.05], 2-Carbamoylethylmercapturic acid (AAMA) [WMD 66.47, 95% CI (27.49 to 105.46), p < 0.05], 4-Hydroxy-2-buten-1-yl-mercapturic acid (MHBMA) [WMD 287.79, 95% CI (-54.47 to 630.04), p > 0.05], 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNAL) [WMD 189.37, 95% CI (78.45 to 300.29), p < 0.05], or N0-nitrosonornicotine (NNN) [WMD 11.66, 95% CI (7.32 to 16.00), p < 0.05]. Conclusion: Urinary bladder cancer markers were significantly higher in traditional tobacco users than in e-cigarette users.Systematic review registration: PROSPERO (CRD42023455600: https://www.crd.york.ac.uk/PROSPERO/).

Analysis of the association between testosterone and cardiovascular disease potential risk factor apolipoprotein B in adult males without cancer: national health and nutrition examination survey 2011-2016.

Background: Over the years, there has been extensive exploration of the association between testosterone and lipid profiles, yet the precise mechanisms underlying their interaction remain incompletely elucidated. Similarly, there is a dearth of research on the correlation between serum apolipoprotein B (apoB) and serum total testosterone (TT), particularly within specific populations. Methods: We conducted a cross-sectional study to assess the relationship between serum TT concentration and serum apoB concentration. Using the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016, we employed weighted generalized linear models, weighted univariate, weighted multivariate analysis, and smooth curve fitting to assist in exploring the relationship between serum TT and apoB. Serum apoB concentration served as the independent variable, and serum TT concentration as the dependent variable. ApoB was divided into four quartiles-Q1 (<0.7g/L, N=691), Q2 (≥0.7g/L to <0.9g/L, N=710), Q3 (≥0.9g/L to <1.1g/L, N=696), and Q4 (≥1.1g/L, N=708)-thereby further solidifying the stable association between the two. Additionally, the application of smooth curve fitting will contribute to a more detailed elucidation of the specific relationship between serum TT concentration and serum apoB concentration under different factors (Drinking, Smoke, Diabetes, Hypertension, and High cholesterol level.). Results: The results indicate a negative correlation between serum TT concentration and apoB concentration (ß=-113.4; 95% CI: -146.6, -80.2; P<0.001). After adjusting for confounding variables, the negative correlation between apoB concentration and TT concentration remains significant (ß=-61.0; 95% CI: -116.7, -5.2; P=0.040). When apoB concentration was converted from a continuous variable to a categorical variable (quartiles: Q1<0.7g/L; Q2:≥0.7g/L to<0.9g/L; Q3:≥0.9g/L to <1.1g/L; Q4: ≥1.1g/L), TT level of participants in the highest quartile (≥1.1g/L) was -47.2 pg/mL (95% CI: -91.2, -3.3; P=0.045) lower than that in the lowest quartile (<0.7g/L). The smooth curve fitting diagram revealed differences in the relationship between TT concentration and apoB among individuals with different cardiovascular disease (CVD) risk factors. Conclusions: This study elucidates a robust inverse correlation between serum TT concentration and apoB concentration, maintaining statistical significance even upon adjustment for confounding factors. These findings present a promising avenue for addressing the prevention and treatment of low testosterone and CVD.

Cancer-Associated Fibroblast-Induced Remodeling of Tumor Microenvironment in Recurrent Bladder Cancer.

Bladder carcinoma (BC) recurrence is a major clinical challenge, and targeting the tumor microenvironment (TME) is a promising therapy. However, the relationship between individual TME components, particularly cancer-associated fibroblasts (CAFs), and tumor recurrence is unclear. Here, TME heterogeneity in primary and recurrent BC is investigated using single-cell RNA sequence profiling of 62 460 cells. Two cancer stem cell (CSC) subtypes are identified in recurrent BC. An inflammatory CAF subtype, ICAM1+ iCAFs, specifically associated with BC recurrence is also identified. iCAFs are found to secrete FGF2, which acts on the CD44 receptor of rCSC-M, thereby maintaining tumor stemness and epithelial-mesenchymal transition. Additionally, THBS1+ monocytes, a group of myeloid-derived suppressor cells (MDSCs), are enriched in recurrent BC and interacted with CAFs. ICAM1+ iCAFs are found to secrete CCL2, which binds to CCR2 in MDSCs. Moreover, elevated STAT3, NFKB2, VEGFA, and CTGF levels in iCAFs reshape the TME in recurrent tumors. CCL2 inhibition in an in situ BC mouse model suppressed tumor growth, decreased MDSCs and Tregs, and fostered tumor immune suppression. The study results highlight the role of iCAFs in TME cell-cell crosstalk during recurrent BC. The identification of pivotal signaling factors driving BC relapse is promising for the development of novel therapies.

Analysis of the association between serum antiaging humoral factor klotho and cardiovascular disease potential risk factor apolipoprotein B in general population.

Cardiovascular disease (CVD) is a prevalent health issue, and various risk factors contribute to its development, including blood lipids, blood pressure, diabetes, smoking, and alcohol consumption. Apolipoprotein B (ApoB) is related to CVD. ApoB is present on the surface of low-density lipoprotein (LDL), and its cellular recognition and LDL uptake are mainly achieved through recognition. It plays a crucial role in the diagnosis and treatment of CVD. This study aims to investigate the relationship between Klotho and ApoB in the general population of the United States as the correlation between serum Klotho and apoB is currently unknown. These findings could potentially guide the development of future treatments for CVD. This study utilized data from the National Health and Nutrition Examination Survey (NHANES) collected between 2007 and 2016. A linear regression model and smooth curve fitting were conducted to analyze the relationship between serum Klotho and apoB. The results indicate a negative correlation between serum Klotho concentration and apoB concentration (ß = -71.7; 95% confidence interval [CI]: -120.8, -22.6; P = .005). After adjusting for confounding variables, the negative correlation between apoB concentration and serum Klotho concentration became more significant (ß = -91.8; 95% CI: -151.3, -32.2; P = .004). When apoB concentration was converted from a continuous variable to a categorical variable (tertiles: T1 <0.8 g/L; T2: ≥0.8 g/L to <1.0 g/L; T3: ≥1.0 g/L), the serum klotho level of participants in the highest tertile (≥1.0 g/L) was -44.8 pg/mL (95% CI: -86.3, -3.2; P = .040) lower than that in the lowest tertile (<0.8 g/L). The smooth curve fitting diagram revealed differences in the relationship between serum Klotho concentration and apoB among individuals with different CVD risk factors. This study demonstrates a significant negative correlation between serum Klotho concentration and apoB concentration, even after controlling for confounding factors. The findings suggest that serum Klotho and apoB may be involved in the development of CVD, and targeting these factors could be a potential approach for CVD prevention and treatment.

Single-Cell Transcriptome Comparison of Bladder Cancer Reveals Its Ecosystem.

Bladder carcinoma (BLCA) is a highly heterogeneous disease, and the underlying biological behavior is still poorly understood. Here, single-cell RNA sequencing was performed on four clinical samples of different grades from three patients, and 26,792 cell transcriptomes were obtained revealing different tumor ecosystems. We found that N-glycan biosynthesis pathway was activated in high-grade tumor, but TNF-related pathway was activated in cystitis glandularis. The tumor microenvironment (TME) of different samples showed great heterogeneity. Notably, cystitis glandularis was dominated by T cells, low-grade and high-grade tumors by macrophages, while TME in patient with high-grade relapse by stromal cells. Our research provides single-cell transcriptome profiles of cystitis glandularis and BLCA in different clinical states, and the biological program revealed by single-cell data can be used as biomarkers related to clinical prognosis in independent cohorts.

microRNA-27b inhibits cell proliferation and invasion in bladder cancer by targeting engrailed-2.

BACKGROUND: Bladder cancer is considered a malignant tumour characterised by great heterogeneity. Engrailed-2 may be a gene implicated in bladder cancer. Bioinformatics analysis found base pair complementation between microRNA-27b and engrailed-2. The present study aimed to investigate the reciprocal association between microRNA-27b and engrailed-2 in bladder cancer. METHODS: The microRNA-27b and the protein of engrailed-2 in the tissues and cells of the bladder were detected. The processes of apoptosis, proliferation, invasion, and migration of tumour cells were evaluated. The co-action between microRNA-27b and engrailed-2 was detected by a luciferase reporter system. Finally, the interaction between microRNA-27b and engrailed-2 was further verified in vivo. RESULTS: The study found that the expression level of microRNA-27b is lower in bladder cancer tissues and cells than that in neighbouring ordinary tissues, whereas the opposite outcome was observed regarding the expression level of engrailed-2. Furthermore, microRNA-27b expression level is not significantly linked to the age of patients with bladder cancer; however, it is significantly associated with the clinicopathological grade of bladder cancer. Notably, engrailed-2 is negatively regulated by microRNA-27b. Transfection with microRNA-27b was associated with a significant reduction in the activity of bladder cancer cells and promoted apoptosis, while engrailed-2 restoration effectively reversed the above effects of microRNA-27b on bladder cancer in vitro and in vivo. CONCLUSIONS: In conclusion, engrailed-2 is engaged in the development and process of bladder cancer through the negative mediation of microRNA-27b; additionally, microRNA-27b/engrailed-2 could form a signalling pathway with a significant effect on the process of bladder cancer.

Photoactivated H2 Nanogenerator for Enhanced Chemotherapy of Bladder Cancer.

Hydrogen gas can mitigate oxidative stress in many diseases and is regarded to be safe and free of side effects. Inspired by a metalloenzyme in a variety of microorganisms, here, we propose a photoactivated H2 nanogenerator that comprises a fluorinated chitosan (FCS), a chemotherapeutic drug (gemcitabine, GEM), and a catalyst of H2 production ([FeFe]TPP) that can form self-assembled [FeFe]TPP/GEM/FCS nanoparticles (NPs). The [FeFe]TPP/GEM/FCS NPs exhibit excellent transmucosal and tumor cell penetration capacities after intravesical instillation into the bladder and can efficiently produce H2 gas in situ upon 660 nm laser irradiation, which significantly enhances the efficacy of hydrogen chemotherapy of cancer in vitro and in vivo. Moreover, we discover that H2 gas in hydrogen chemotherapy can inhibit mitochondrial function, hinder ATP synthesis, and cause a reduction of the P-gp efflux pump function, which finally attenuates P-gp protein drug transport capacity in cancer cells. This photoactivated H2 evolution in situ to improve the therapeutic efficacy of chemotherapy of bladder cancer may present an effective hydrogen chemotherapy strategy for cancer treatment.

Fluorinated Chitosan To Enhance Transmucosal Delivery of Sonosensitizer-Conjugated Catalase for Sonodynamic Bladder Cancer Treatment Post-intravesical Instillation.

Sonodynamic therapy (SDT) is a noninvasive ultrasound-triggered therapeutic strategy for site-specific treatment of tumors with great depth penetration. The design of nano-sonosensitizers suitable for SDT treatment of bladder cancer (BCa) post-intravesical instillation has not yet been reported. Herein, a transmucosal oxygen-self-production SDT nanoplatform is developed to achieve highly efficient SDT against BCa. In this system, fluorinated chitosan (FCS) is synthesized as a highly effective nontoxic transmucosal delivery carrier to assemble with meso-tetra(4-carboxyphenyl)porphine-conjugated catalase (CAT-TCPP). The formed CAT-TCPP/FCS nanoparticles after intravesical instillation into the bladder cavity exhibit excellent transmucosal and intratumoral penetration capacities and could efficiently relieve hypoxia in tumor tissues by the catalase-catalyzed O2 generation from tumor endogenous H2O2 to further improve the therapeutic efficacy of SDT to ablate orthotopic bladder tumors under ultrasound. Our work presents a nano-sonosensitizer formulation with FCS to enhance transmucosal delivery and intratumoral diffusion and CAT to improve tumor oxygenation, promising for instillation-based SDT to treat bladder tumors without the concern of systemic toxicity.

Learning Curve for the Tension-Free Vaginal Tape-Obturator Procedure for Female Stress Urinary Incontinence: A Prospective Single-Surgeon Study.

Objective: To evaluate the learning curve in an untrained resident surgeon for the initial case series of tension-free vaginal tape-obturator (TVT-O) to treat stress urinary incontinence. Materials and Methods: A retrospective observational study was conducted in Changhai Hospital, Shanghai, China, between March 2014 and June 2018. All consecutive women included were treated by the TVT-O procedure performed by one surgeon working under the supervision of an expert surgeon. Clinical features, estimated blood loss, operative time, postoperative hospital stay, total hospital stay, adverse events, and subjective and objective cure rates were recorded. Learning curve patterns were estimated to determine the number of cases to reach a plateau using the moving average method. Results: In total, 188 patients were included for analysis. Patients ranged from 39 to 91 years, with the average age of 57.5 ± 9.7 years. The mean operative time was 32.0 minutes (range 20-60). Operative time and blood loss decreased with increase in the level of expertise, whereas postoperative hospital stay and total hospital stay were not influenced by the number of procedures performed. The number of cases required to reach a plateau was ∼30. Objective cure rate and subjective cure rate were achieved in 88.7% and 88.2% at 12 months, respectively. Groin pain was the most common postoperation complication, which continued to be present in 11.7% patients at 12 months after surgery. Conclusions: The TVT-O procedure showed encouraging objective and subjective outcomes and low complication rates, even at the initial stage of the learning curve. Thirty cases were required for a naïve resident surgeon to learn TVT-O procedures. However, long-term outcome and complications caused by the synthetic sling still need further follow-up.