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Objective: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. Design, Patients and Measurements: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. Results: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p <.001), had larger tumours (2.9 vs. 1.8 cm, p <.001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p <.001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p =.003), hypertension (50.0% vs. 31.7%, p =.041) and catecholamine‐related symptoms (37.9% vs. 17.5%, p =.012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p =.013), micturition spells (OR = 6.79, p =.007), hypertension (OR = 3.98, p =.011), and sweating (OR = 41.72, p =.013) increased the probability of initiating presurgical biochemical testing. Conclusions: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis. [ABSTRACT FROM AUTHOR]

Aim: To examine association between subgingival microbial signatures and levels of cognitive impairment in older adults. Materials and Methods: We analysed subgingival plaque samples and 16S ribosomal RNA sequences for microbiota among 165 participants (normal controls [NCs]: 40, subjective cognitive decline [SCD]: 40, mild cognitive impairment [MCI]: 49 and dementia: 36). Results: The bacterial richness was lower among individuals with worse cognitive function, and subgingival microbial communities differed significantly among the four groups. Declining cognitive function was associated with decreasing relative abundance of genera Capnocytophaga, Saccharibacteria_genera_incertae_sedis, Lautropia and Granulicatella, and increasing abundance of genus Porphyromonas. Moreover, there were differentially abundant genera among the groups. Random forest model based on subgingival microbiota could distinguish between cognitive impairment and NC (AUC = 0.933, 95% confidence interval 0.873–0.992). Significant correlations were observed between oral microbiota and sex, Montreal Cognitive Assessment (MoCA) score and Mini‐Mental State Examination score. Partial correlation analysis showed that Leptotrichia and Burkholderia were closely negatively associated with the MoCA score after adjusting for multiple covariates. Gene function was not significantly different between SCD and NC groups, whereas three homozygous genes were altered in MCI patients and two in dementia patients. Conclusions: This is the first study to demonstrate an association between the composition, function and metabolic pathways of subgingival microbiota and different levels of cognitive function among older individuals. Future cohort studies should assess its diagnostic usefulness for cognitive impairment. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of 3.0T MRI multi‐directional diffusion‐weighted imaging (DWI) combined with T2WI morphological features and lesion distribution in preoperative prediction of muscle layer invasion of bladder cancer (BC) and the correlation with postoperative Ki‐67. Materials and Methods: This retrospective study enrolled patients with BC between 2019 and 2021. Patients with muscular invasive bladder cancer (MIBC) or non‐muscular invasive BC (NMIBC) were also analyzed by preoperative 3.0T MRI aFostic efficacy. Results: A total of 186 patients were enrolled. About 27 patients with MIBC (35 lesions in total) and 62 with NMIBC (99 lesions in total). We found the tumor with a larger size, a wide base, and a smaller apparent dispersion coefficient (ADC) value and normalized ADC(nADC) value, without a stalk, presenting a greater risk of muscle invasion. ADC value, nADC value, maximum diameter, and stalk were independently associated with muscle invasion. Lesions located at the bladder fundus or involvement of multiple sites were independently associated with muscle invasion compared to the bladder body. In combination with morphological features, the AUCs of ADC and nADC showed accuracies of 0.925 and 0.947–0.951, respectively. TADC and nTADC showed the best diagnostic efficacy in multiple respects. KI‐67 LI was negatively correlated with ADC and nADC values. Conclusions: This is the first report in which we found Multi‐directional DWI combined with T2WI in 3.0T MRI can be used to predict the muscle layer invasion of bladder cancer. ADC values reflect the muscular invasion of bladder cancer and show a moderate negative correlation with Ki‐67. It is especially suitable for bladder cancer patients with renal insufficiency or tumor recurrence. [ABSTRACT FROM AUTHOR]

Bladder cancer is a common malignancy in the urinary system. Defects of drug molecules in bladder during treatment, such as passive diffusion, rapid clearance of periodic urination, poor adhesion and permeation abilities, lead to low delivery efficiency of conventional drugs and high recurrence rate of disease. In this study, we designed multi‐responsive mesoporous polydopamine (PDA) composite nanorods cooperating with nano‐enzyme and photosensitiser for intensive immunotherapy of bladder cancer. The strongly adhesive mesoporous PDA with wheat germ agglutinin on nanoparticles could specifically adhere to epithelial glycocalyx and made the nanoparticles aggregate in urinary pathways. Meanwhile, 2,3‐dimethylmaleic anhydride could be hydrolysed in acidic conditions of tumour microenvironment, giving it a positive charge (charge reversal), which is more amenable to enter cancer cells. Afterwards, manganese dioxide nanorods could catalyse the reaction of excess H2O2 in tumour microenvironment to generate active oxygen, so as to change the hypoxic environment in tumour, and achieve a pH‐responsive for slow release of PD‐L1. After the ICG was irradiated by infrared light, a large amount of singlet oxygen was generated, thereby enhancing the therapeutic effect and reducing toxicity in vivo. Besides, mesoporous PDA with indocyanine green photothermal agent could have a local heat up quickly under the near‐infrared light to kill cancer cells, thereby enhancing therapeutic efficacy. Accordingly, this mesoporous PDA composite nanorods shed a light on bladder tumour treatment. [ABSTRACT FROM AUTHOR]

Background. Prostate cancer is one of the most common malignancies in men. Protein ubiquitination is an important mechanism for regulating protein activity and level in vivo. We aimed to study the mechanism of SEPT6 and UBC action in prostate cancer to identify new targets. Methods. The ubiquitin-protein and the ubiquitin coding gene UBA52, UBA80, UBB, and UBC expressions were detected in clinical tissues and cells. Overexpression and knockdown of UBC were performed in prostate cancer DU145 cells. Cell Counting Kit 8 (CCK-8) assay was performed to detect cell proliferation. Cell cycle at 24 h was detected by flow cytometry. Clonal formation assay was used to measure cell clone number. Immunofluorescence (IF) was performed to detect the colocalization of SEPT6 and UBC in prostate cancer cells. Next, we overexpressed or knocked down SEPT6 expression in DU145 cells. Pearson correlation coefficient was applied to analyze the relationship between SEPT6 and UBC in prostate cancer tissue. oe-SEPT6+oe-UBC coexpressing cells were constructed to detect the upstream and downstream relationship between SEPT6 and UBC on prostate cancer cells. The tumor formation experiment was performed to explore SEPT6/UBC effect on prostate cancer. Results. UBC was upregulated in prostate cancer tissues and cells. Overexpression of UBC promoted cell survival and proliferation. IF revealed the colocalization of SEPT6 and UBC in prostate cancer cells. UBC expression decreased after oe-SEPT6, while increased after sh-SEPT6, indicating that UBC was downstream of SEPT6. Pearson correlation coefficient analysis showed that SEPT6 was negatively correlated with UBC in prostate cancer tissues. SEPT6 as an upstream gene of UBC regulated prostate cancer cell behavior through UBC. The tumor formation experiment showed that SEPT6 could inhibit tumor growth. Conclusion. In general, SEPT6 inhibited UBC expression, thereby reducing the overall ubiquitination level, affecting the expression level of downstream cell proliferation-related genes, and then affecting the progression of prostate cancer. [ABSTRACT FROM AUTHOR]

Previous studies have established the efficacy of irradiated cancer cells overexpressing GM-CSF or IL-21 as a vaccine. Here we examined whether the vaccine efficacy was greater when both factors were overexpressed together. MB49 bladder cancer cells were transfected with expression plasmid pT7TS encoding mouse GM-CSF and human IL-21, and then irradiated with 100 Gy at 4 days later. The cells (1×107 per animal) were injected subcutaneously into C57BL/6 mice at 0, 4, 8, and 12 days after inoculation with MB49 tumor xenografts. Control animals were injected with MB49 cells transfected with pT7TS encoding GM-CSF or IL-21 on its own. Tumor growth was monitored for 45 days and compared among the groups using repeated-measures ANOVA. Vaccination with irradiated MB49 cells did not affect xenograft growth. Vaccination with irradiated cells overexpressing GM-CSF or IL-21 alone significantly inhibited tumor growth and led to significantly more CD4+ CD8+ T cells and fewer CD4+ Foxp3+ T cells in the spleen and xenograft. These effects were even greater following vaccination with irradiated cells overexpressing both GM-CSF and IL-21. Irradiated bladder cancer cells overexpressing both GM-CSF and IL-21 are more effective than cells expressing either factor alone as a vaccine against bladder cancer. [ABSTRACT FROM AUTHOR]

We focused on studying the effects of a key miRNA-mRNA axis in bladder urothelial carcinoma (BUC). Firstly, miRNAs and mRNAs differentially expressed in BUC were analyzed. Clinical information in the TCGA database was used for survival analysis, and the regulator of miRNA-93-5p was predicted. miRNA-93-5p and KLF9 mRNA expression were detected by qRT-PCR. Protein level detection and targeting measurement were, respectively, achieved by western blot and dual-luciferase approaches. The proliferative, invasive, and migratory abilities were tested through CCK-8, Transwell, and wound healing methods. Cell apoptosis in each group was detected through flow cytometry. As discovered, miRNA-93-5p level was markedly high in BUC cells while KLF9 expression was remarkably low. miRNA-93-5p overexpression promoted BUC cell abilities. Besides, miRNA-93-5p inhibited KLF9 expression. Furthermore, KLF9 overexpression dramatically attenuated such promotion on cancer cell abilities. On the whole, miRNA-93-5p/KLF9 axis facilitated BUC progression, offering a new potential target for BUC patients. [ABSTRACT FROM AUTHOR]

Background. lncRNAs affect adaptive and innate immunity of cancer via mediating functional states of immune cells, genes, and pathways. Nonetheless, little is known about the molecular mechanism of lncRNA-mediated CD8+ T cell immune infiltration in progression of clear cell renal cell carcinoma (ccRCC). We designed this work to investigate the role of LINC00887 in regulating CD8+ T cell immune infiltration in ccRCC. Methods. Correlation between LINC00887 and immune factors and the expression level of LINC00887 in ccRCC were analyzed by bioinformatics methods (TCGA-KIRC database, "edgeR" package, "clusterProfiler" package, and "CIBERSORT" package). LINC00887 expression in ccRCC was examined via RT-qPCR. The cytokilling capacity of CD8+ T cells was evaluated by the lactate dehydrogenase assay. The apoptotic ability of CD8+ T cells was measured by flow cytometry. The chemotactic ability of CD8+ T cells was revealed by chemotaxis assay. CXCR3, CXCL9, and CXCL10 levels were assessed by RT-qPCR. Results. As suggested by bioinformatics analysis, LINC00887 was markedly upregulated in ccRCC patients and associated with expression of immune-suppression molecule, thereby abating the immune infiltration level of CD8+ cells in tumor tissue. As revealed by cellular assay, LINC00887 was upregulated in ccRCC cells, and knockdown of LINC00887 resulted in a decreased PD-L1 expression, increased CD8+ T cell toxicity, decreased apoptotic levels, and enhanced chemotaxis. Moreover, we found that LINC00887 exhibited inhibitory effect on immune infiltration of CD8+ cells in clinical tissues. Conclusions. The results of this study suggested that LINC00887 promoted ccRCC progression by inhibiting immune infiltration of CD8+ T cells, providing new insights into pathogenesis of ccRCC and suggesting LINC00887 being a promising immunotherapy target for ccRCC. [ABSTRACT FROM AUTHOR]