Lactobacillus-Polydopamine System for Targeted Drug Delivery in Overactive Bladder: Evidence from Bladder Cell Spheroids, Rat Models, and Urinary Microbiome Profiling.

Introduction: Overactive bladder (OAB) is a highly prevalent condition with limited treatment options due to poor efficacy, side effects, and patient compliance. Novel drug delivery systems that can target the bladder wall may improve OAB therapy. Methods: We explored a polydopamine (PDA)-coated lactobacillus platform as a potential carrier for localized OAB treatment. Urinary microbiome profiling was performed to identify the presence of lactobacillus in healthy and OAB groups. Lactobacillus-PDA nanoparticles were synthesized and characterized by electron microscopy and spectrophotometry. A rat bladder perfusion model and human bladder smooth muscle cell spheroids were used to assess the distribution and penetration of the nanoparticles. The efficacy of the Lactobacillus-PDA system (LPS) for delivering the antimuscarinic drug solifenacin was evaluated in an OAB rat model. Results: Urinary microbiome profiling revealed lactobacillus as a dominant genus in both healthy and OAB groups. The synthesized Lactobacillus-PDA nanoparticles exhibited uniform size and optical properties. In the rat bladder perfusion model, the nanoparticles distributed throughout the bladder wall and smooth muscle without toxicity. The nanoparticles also penetrated human bladder smooth muscle cell spheroids. In the OAB rat model, LPS facilitated the delivery of solifenacin and improved treatment efficacy. Discussion: The results highlight LPS as a promising drug carrier for targeted OAB therapy via penetration into bladder tissues. This bacteriotherapy approach may overcome limitations of current systemic OAB medications. Lactobacillus, a probiotic bacterium present in the urinary tract microbiome, was hypothesized to adhere to and penetrate the bladder wall when coated with PDA nanoparticles, making it a suitable candidate for localized drug delivery.

Evaluating the Lower Urinary Tract Syndrome with a Telemedicine Application: An Exploration of the Electronic Audiovisual Prostate Symptom Score.

Background: The Visual Prostate Symptom Score (VPSS) is used for the assessment of lower urinary tract symptoms (LUTS). It is usually administered by general practitioners (GPs), but in these cases, outcomes do not seem to be reflecting the real conditions of a patient well, with consequent risks of misestimations and misinterpretations. We developed an electronic audiovisual version of VPSS (EPSS), a new symptom scale based on a telemedicine mobile light-based app. The aim of this study is to test and evaluate its reliability. Methods: We enrolled male patients aged between 50 and 80 years across 24 community-based healthcare facilities in Guangzhou, China. Patients were asked to complete the Chinese version of VPSS and EPSS before consultation with the urology specialists. Patients were divided into two groups based on age. First, we analyzed the rate of full understanding of EPSS using a chi-square test. Then, we analyzed the difference between each score of EPSS, VPSS, and outcomes measured by specialists, used as the reference score (RS). Finally, the outcomes were analyzed with the Spearman test and Bartlett test separately. Results: Seventy-nine male patients were included (mean age 70.42 years). Patients were divided into two groups: group 1 (>70 years, n = 40) and group 2 (<70 years, n = 39). The full-understanding rates in groups 1 and 2 were 50% and 64.1%, respectively. No significant differences were noted between groups (p = 0.206). A t-test was presented between each question of VPSS, EPSS, and RS. All questions did not display significant differences (p > 0.05); total scores from the three scales had no significant differences in the evaluation of LUTS. We further explored the variations of choices made by patients in different scales. Spearman's test among VPSS, EPSS, and RS showed positive correlations, and coefficients of the total score were 0.92, 0.91, and 0.93 (p < 0.05). Conclusion: EPSS can be easily used in a significant number of patients and showed correlation with the VPSS and RS. Moreover, certain items resulted in better performance than VPSS. The results showed that EPSS could be a valuable option for both patients and GPs monitoring LUTS and particularly helpful when teleconsultations are considered, especially during the COVID-19 pandemic.

Blood-Brain Barrier, Cell Junctions, and Tumor Microenvironment in Brain Metastases, the Biological Prospects and Dilemma in Therapies.

Brain metastasis is the most commonly seen brain malignancy, frequently originating from lung cancer, breast cancer, and melanoma. Brain tumor has its unique cell types, anatomical structures, metabolic constraints, and immune environment, which namely the tumor microenvironment (TME). It has been discovered that the tumor microenvironment can regulate the progression, metastasis of primary tumors, and response to the treatment through the particular cellular and non-cellular components. Brain metastasis tumor cells that penetrate the brain-blood barrier and blood-cerebrospinal fluid barrier to alter the function of cell junctions would lead to different tumor microenvironments. Emerging evidence implies that these tumor microenvironment components would be involved in mechanisms of immune activation, tumor hypoxia, antiangiogenesis, etc. Researchers have applied various therapeutic strategies to inhibit brain metastasis, such as the combination of brain radiotherapy, immune checkpoint inhibitors, and monoclonal antibodies. Unfortunately, they hardly access effective treatment. Meanwhile, most clinical trials of target therapy patients with brain metastasis are always excluded. In this review, we summarized the clinical treatment of brain metastasis in recent years, as well as their influence and mechanisms underlying the differences between the composition of tumor microenvironments in the primary tumor and brain metastasis. We also look forward into the feasibility and superiority of tumor microenvironment-targeted therapies in the future, which may help to improve the strategy of brain metastasis treatment.

Resequencing a core collection of upland cotton identifies genomic variation and loci influencing fiber quality and yield.

Upland cotton is the most important natural-fiber crop. The genomic variation of diverse germplasms and alleles underpinning fiber quality and yield should be extensively explored. Here, we resequenced a core collection comprising 419 accessions with 6.55-fold coverage depth and identified approximately 3.66 million SNPs for evaluating the genomic variation. We performed phenotyping across 12 environments and conducted genome-wide association study of 13 fiber-related traits. 7,383 unique SNPs were significantly associated with these traits and were located within or near 4,820 genes; more associated loci were detected for fiber quality than fiber yield, and more fiber genes were detected in the D than the A subgenome. Several previously undescribed causal genes for days to flowering, fiber length, and fiber strength were identified. Phenotypic selection for these traits increased the frequency of elite alleles during domestication and breeding. These results provide targets for molecular selection and genetic manipulation in cotton improvement.