New TRUS Techniques and Imaging Features of PI-RADS 4 or 5: Influence on Tumor Targeting

PurposeTo determine if the new transrectal ultrasound (TRUS) techniques and imaging features contribute to targeting Prostate Imaging and Reporting and Data System (PI-RADS) 4 or 5.Materials and MethodsBetween December 2018 and February 2020, 115 men underwent cognitive biopsy by radiologist A, who was familiar with the new TRUS findings and biopsy techniques. During the same period, 179 men underwent magnetic resonance imaging–TRUS image fusion or cognitive biopsy by radiologist B, who was unfamiliar with the new biopsy techniques. Prior to biopsy, both radiologists knew MRI findings such as the location, size, and shape of PI-RADS 4 or 5. We recorded how many target biopsies were performed without systematic biopsy and how many of these detected higher Gleason score (GS) than those detected by systematic biopsy. The numbers of biopsy cores were also obtained. Fisher Exact or Mann–Whitney test was used for statistical analysis.ResultsFor PI-RADS 4, target biopsy alone was performed in 0% (0/84) by radiologist A and 0.8% (1/127) by radiologist B (p>0.9999). Target biopsy yielded higher GSs in 57.7% (30/52) by radiologist A and 29.5% (23/78) by radiologist B (p = 0.0019). For PI-RADS 5, target biopsy alone was performed in 29.0% (9/31) by radiologist A and 1.9% (1/52) by radiologist B (p = 0.0004). Target biopsy yielded higher GSs in 50.0% (14/28) by radiologist A and 18.2% (8/44) by radiologist B (p = 0.0079). Radiologist A sampled fewer biopsy cores than radiologist B (p = 0.0008 and 0.0023 for PI-RADS 4 and 5), respectively.ConclusionsPI-RADS 4 or 5 can be more precisely targeted if the new TRUS biopsy techniques are applied

IFT46 plays crucial roles in craniofacial and cilia development

The intraflagellar transport (IFT) system is essential for bidirectional movement of ciliary components from the basal body to the tip beneath the ciliary sheath and is conserved for cilia and flagella formation in most vertebrates. IFT complex A is involved in anterograde trafficking, whereas complex B is involved in retrograde trafficking. IFT46 is well known as a crucial component of IFT complex B, however, its developmental functions are poorly understood. In this study, we investigated the novel functions of IFT46 during vertebrate development, especially, ciliogenesis and neurogenesis, because IFT46 is strongly expressed in both multiciliated cells of epithelial and neural tissues. Knockdown of IFT46 using morpholino microinjections caused shortening of the body axis as well as the formation of fewer and shorter cilia. Furthermore, loss of IFT46 down-regulated the expression of the neural plate and neural tube markers, thus may influence Wnt/planar cell polarity and the sonic hedgehog signaling pathway during neurogenesis. In addition, loss of IFT46 caused craniofacial defects by interfering with cartilage formation. In conclusion, our results depict that IFT46 plays important roles in cilia as well as in neural and craniofacial development.clos

Peroxiredoxin5 controls vertebrate ciliogenesis by modulating mitochondrial ROS

Aims: Peroxiredoxin5 (Prdx5) - a thioredoxin peroxidase is an antioxidant enzyme that is widely studied for its antioxidant properties and protective roles in neurological and cardiovascular disorders. The present study is aimed to investigate the functional significance of Prdx5 in mitochondria and to analyze its roles in ciliogenesis during the process of vertebrate development. Results: We found that several Prdx genes were strongly expressed in multiciliated cells in developing Xenopus embryos, and their peroxidatic functions were crucial for normal cilia development. Depletion of Prdx5 increased levels of cellular ROS, consequently leading to mitochondrial dysfunction and abnormal cilia formation. Proteomic and transcriptomic approaches revealed that excessive ROS accumulation upon Prdx5 depletion subsequently reduced the expression level of pyruvate kinase (PK), a key metabolic enzyme in energy production. We further confirmed that the promotor activity of PK was significantly reduced upon Prdx5 depletion and that the reduction in PK expression and its promoter activity led to ciliary defects observed in Prdx5-depleted cells. Innovation: Our data revealed the novel relationship between ROS and Prdx5 and the consequent effects of this interaction on vertebrate ciliogenesis. The normal process of ciliogenesis is interrupted by the Prdx5 depletion resulting in excessive ROS levels suggesting cilia as vulnerable targets of ROS. Conclusion: Prdx5 play protective roles in mitochondria and is critical for normal cilia development by regulating the levels of ROS. The loss of Prdx5 is associated with excessive production of ROS resulting in mitochondrial dysfunction and aberrant ciliogenesis