Severe bronchiectasis resulting from chronic bacterial bronchitis and bronchopneumonia in a jungle cat.

Bronchiectasis is irreversible bronchial dilation that can be congenital or acquired secondary to chronic airway obstruction. Feline bronchiectasis is rare and, to our knowledge, has not been reported previously in a non-domestic felid. An ~10-y-old female jungle cat (Felis chaus) was presented for evaluation of an abdominal mass and suspected pulmonary metastasis. The animal died during exploratory laparotomy and was submitted for postmortem examination. Gross examination revealed consolidation of the left caudal lung lobe and hila of the cranial lung lobes. Elsewhere in the lungs were several pale-yellow pleural foci of endogenous lipid pneumonia. On cut section, there was severe distension of bronchi with abundant white mucoid fluid. The remaining lung lobes were multifocally expanded by marginal emphysema. Histologically, ectatic bronchi, bronchioles, and fewer alveoli contained degenerate neutrophils, fibrin, and mucin (suppurative bronchopneumonia) with rare gram-negative bacteria. Aerobic culture yielded low growth of Proteus mirabilis and Escherichia coli. There was chronic bronchitis, marked by moderate bronchial gland hyperplasia, lymphoplasmacytic inflammation, and lymphoid hyperplasia. The palpated abdominal mass was a uterine endometrial polyp, which was considered an incidental, but novel, finding. Chronic bronchitis and bronchopneumonia should be considered as a cause of bronchiectasis and a differential diagnosis for respiratory disease in non-domestic felids.

Specific subsets of urothelial bladder carcinoma infiltrating T cells associated with poor prognosis.

Comprehensive investigation of tumor-infiltrating lymphocytes in cancer is crucial to explore the effective immunotherapies, but the composition of infiltrating T cells in urothelial bladder carcinoma (UBC) remains elusive. Here, single-cell RNA sequencing (scRNA-seq) were performed on total 30,905 T cells derived from peripheral blood, adjacent normal and tumor tissues from two UBC patients. We identified 18 distinct T cell subsets based on molecular profiles and functional properties. Specifically, exhausted T (TEx) cells, exhausted NKT (NKTEx) cells, Ki67+ T cells and B cell-like T (B-T) cells were exclusively enriched in UBC. Additionally, the gene signatures of TEx, NKTEx, Ki67+ T and B-T cells were significantly associated with poor survival in patients with BC and various tumor types. Finally, IKZF3 and TRGC2 are the potential biomarkers of TEx cells. Overall, our study demonstrated an exhausted context of T cells in UBC, which layed a theoretical foundation for the development of effective tumor immunotherapies.

Hope and challenge: Precision medicine in bladder cancer.

Bladder cancer (BC) is a complex disease and could be classified into nonmuscle-invasive BC (NMIBC) or muscle-invasive BC (MIBC) subtypes according to the distinct genetic background and clinical prognosis. Until now, the golden standard and confirmed diagnosis of BC is cystoscopy and the major problems of BC are the high rate of recurrence and high costs in the clinic. Recent molecular and genetic studies have provided perspectives on the novel biomarkers and potential therapeutic targets of BC. In this article, we provided an overview of the traditional diagnostic approaches of BC, and introduced some new imaging, endoscopic, and immunological diagnostic technology in the accurate diagnosis of BC. Meanwhile, the minimally invasive precision treatment technique, immunotherapy, chemotherapy, gene therapy, and targeted therapy of BC were also included. Here, we will overview the diagnosis and therapy methods of BC used in clinical practice, focusing on their specificity, efficiency, and safety. On the basis of the discussion of the benefits of precision medicine in BC, we will also discuss the challenges and limitations facing the non-invasive methods of diagnosis and precision therapy of BC. The molecularly targeted and immunotherapeutic approaches, and gene therapy methods to BC treatment improved the prognosis and overall survival of BC patients.

Circular RNA cTFRC acts as the sponge of MicroRNA-107 to promote bladder carcinoma progression.

BACKGROUND: Circular RNA (circRNA) represents a broad and diverse endogenous RNAs that can regulate gene expression in cancer. However, the regulation and function of bladder cancer (BC) circRNAs remain largely unknown. METHODS: Here we generated circRNA microarray data from three BC tissues and paired non-cancerous matched tissues, and detected circular RNA-cTFRC up-regulated and correlated with tumor grade and poor survival rate of BC patients. We subsequently performed functional analyses in cell lines and an animal model to support clinical findings. Mechanistically, we demonstrated that cTFRC could directly bind to miR-107 and relieve suppression for target TFRC expression. RESULTS: We detected circular RNA-cTFRC up-regulated and correlated with tumor grade and poor survival rate of BC patients. Knock down of cTFRC inhibited invasion and proliferation of BC cell lines in vitro and tumor growth in vivo. Furthermore, the expression of cTFRC correlated with TFRC and negatively correlated with miR-107 both in BC cell lines and BC clinical samples. In addition, up-regulation of cTFRC promoted TFRC expression and contributed to an epithelial to mesenchymal transition phenotype in BC cells. Finally, we found that cTFRC acts as a competing endogenous RNA (ceRNA) for miR-107 to regulate TFRC expression. CONCLUSIONS: cTFRC may exert regulatory functions in BC and may be a potential marker of BC diagnosis or progression.

Enhanced fluorescent intensity of magnetic-fluorescent bifunctional PLGA microspheres based on Janus electrospraying for bioapplication.

Microspheres with magnetic-fluorescent functions have received attention due to fluorescent tracking and target positioning. To improve the accuracy of optical imaging and the fluorescent tracking of drug release, it is essential to enhance the fluorescent intensity of microparticles. Magnetic-fluorescent bifunctional poly lactic-co-glycolic acid (PLGA) Janus microspheres [PLGA/TbLa3(Bim)12]//[PLGA/Fe3O4] with double chambers were fabricated with the double-needle electrospraying method. The fluorescent drug TbLa3(Bim)12 with dual rare earth ions was encapsulated in one chamber, while Fe3O4 magnetic nanoparticles (Fe3O4 MNPs) were simultaneously encapsulated in another chamber. In comparison, magnetic-fluorescent PLGA composite microspheres PLGA/TbLa3(Bim)12/Fe3O4 were also prepared, which encapsulated fluorescent drugs TbLa3(Bim)12 with dual rare earth (RE) ions and Fe3O4 MNPs in one chamber. The fluorescent intensity at 542 nm of Janus microspheres was about three times higher than that of composite microspheres due to a decrease in contact between fluorescent-labeling RE drug and MNPs. The fluorescent intensities of Janus microspheres with different contents of Fe3O4 MNPs and TbLa3(Bim)12 were investigated. Furthermore, the magnetic properties, thermostability, cell toxicity and hemolytic properties of Janus microspheres were also assayed to conduct a tentative exploration of their bioapplication. The Janus microspheres provide many opportunities for application in biofields such as drug delivery.

Development of Magnetic-Fluorescent Bifunctional Drug Delivery System with Dual Drug Content and Enhanced Fluorescence.

The drug delivery system incorporating magnetic particles and fluorescent marker would be uniquely effective for magnetic targeting and fluorescent tracing. In order for the fluorescent signals to reflect the drug delivery accurately, the separation of the fluorescent label and drugs must be counteracted. The objective of the current study was to design a method of binding drugs to the fluorescent material so that the drug diffusion and delivery could be monitored precisely. To obtain fluorescently-labeled drugs, complexes of the rare earth ion with a single drug benzimidazole (Tb(Bim)3), and with combined drugs benzimidazole and aspirin (TbBim(Asp)2) were generated. Subsequently, the magnetic nanoparticles Fe3O4 and TbBim(Asp)2 were encapsulated in chitosan microspheres to prepare magnetic fluorescent bifunctional drug delivery system Fe3O4/TbBim(Asp)2/Chitosan. The intermediate and final products were analyzed by spectroscopy, X-ray diffraction, magnetometry, and electron microscopy, documenting that the newly developed drug-containing nanoparticles exhibited desirable fluorescent, magnetic, and morphologic properties.