Unraveling the Complex Web of Mechanistic Regulation of Versatile NEDD4 Family by Non-Coding RNAs in Carcinogenesis and Metastasis: From Cell Culture Studies to Animal Models.

Discoveries related to an intriguing feature of ubiquitination have prompted a detailed analysis of the ubiquitination patterns in malignant cells. How the "ubiquitinome" is reshaped during multistage carcinogenesis has garnered significant attention. Seminal studies related to the structural and functional characterization of NEDD4 (Neuronal precursor cell-expressed developmentally downregulated-4) have consolidated our understanding at a new level of maturity. Additionally, regulatory roles of non-coding RNAs have further complicated the complex interplay between non-coding RNAs and the members of NEDD4 family. These mechanisms range from the miRNA-mediated targeting of NEDD4 family members to the regulation of transcriptional factors for a broader range of non-coding RNAs. Additionally, the NEDD4-mediated degradation of different proteins is modulated by lncRNAs and circRNAs. The miRNA-mediated targeting of NEDD4 family members is also regulated by circRNAs. Tremendous advancements have been made in the identification of different substrates of NEDD4 family and in the comprehensive analysis of the molecular mechanisms by which various members of NEDD4 family catalyze the ubiquitination of substrates. In this review, we have attempted to summarize the multifunctional roles of the NEDD4 family in cancer biology, and how different non-coding RNAs modulate these NEDD4 family members in the regulation of cancer. Future molecular studies should focus on the investigation of a broader drug design space and expand the scope of accessible targets for the inhibition/prevention of metastasis.

ALD coated polypropylene hernia meshes for prevention of mesh-related post-surgery complications: an experimental study in animals.

In this work, thermal atomic layer deposition (ALD) was used to synthesize vanadium (V)-doped TiO2thin nanofilm on polypropylene (PP) hernia meshes. Multiple layers of (Al2O3+ TiVOx) nano-films were coated on the PP hernia mesh surface to provide a layer with a total thickness of 38 nm to improve its antibacterial properties, thereby, prevent mesh-related post-surgery complications. Highly conformal V-doped TiO2nanofilm were deposited on PP mesh at a temperature of 85 °C. Rats and rabbits have been used to evaluate the tissue reaction on coated PP hernia meshes and biomechanical testing of the healed tissue. Five rabbits and ten rats have been implanted with ALD coated and uncoated (control) PP meshes into the back of rats and abdominal wall of rabbits. Histology of the mesh-adjacent tissues and electron microscopy of the explanted mesh surface were performed to characterize host tissue response to the implanted PP meshes. The effect of V-doped TiO2coating on a living organism and fibroblast functions and bacterial activities were studied. The present results indicated that ALD coating improves adhesion properties and exhibited enhanced antibacterial activity compared to uncoated PP mesh. It was shown that V-doped TiO2coatings were highly effective in inhibitingS. aureusandE. coliadhesion and exhibited excellent antibacterial activity. We found that V-doping of TiO2, unlike bare TiO2, allows generated and further procured strong redox reactions which effectively kills bacteria under visible light. We have reported comparative analysis of the use of undoped (bare) TiO2and V-doped TiO2as a coating for PP meshes and their action in biological environment and preventing biofilms formation compared with uncoated PP meshes. The PP meshes coated with V-doped TiO2showed significantly lower shrinkage rates compared with an identical PP mesh without a coating. We have shown that ALD coatings provide non-adhesive and functional (antibacterial) properties.

Anatomographic Variants of Sphenoid Sinus in Ethiopian Population.

Neurosurgeons often neglect the sphenoid sinus due to its deep location and difficulties in accessing during surgical interventions. Disease of the sphenoid sinus is difficult to diagnose since its presenting symptoms are difficult to recognize. Moreover, compared with other paranasal sinuses, the sphenoid sinus is considered the most variable air sinus in terms of its degree of pneumatization, number and position of inter-sinus septa, and its relationship with the surrounding anatomical structures. Anatomical variations of the sphenoid sinus are significant from a neurosurgical point of view. Understanding of these variations and its relationships with surrounding structures such as the internal carotid artery, optic nerve, and pituitary gland are clinically relevant to minimize injuries associated with surgical procedures that involve sphenoid sinus. We implemented principles of imaging using computed tomography to elucidate any anatomical variations of the sphenoid sinus in the Ethiopian population. We conducted a prospective study in 200 patients with ages 18-79, who underwent scans of the sphenoid sinus at the Tikur Anbessa Referral Teaching Hospital in 2017-2018. Our findings revealed an incidence of anatomographical variations in terms of pneumatization that varied between 2-50%. These variants include 2% conchal, 25.5% presellar, 50% sellar, and 22.5% postsellar pneumatization. We also demonstrated anatomographic variants in terms of septation, 77.5% single complete septa, 11.5% single incomplete, 10% double septa, and 1% absence of septa. In summary, the sellar pneumatization was found to be the most clinically relevant anatomographic variant among Ethiopians participating in the study, of which 90% were tomographically single septated. These variants must be taken into consideration during trans-sphenoidal surgery and knowledge of the variations has clinical implication in minimizing injuries during invasive surgical procedures involving the sphenoid sinus.

Species distribution, genetic diversity and antimicrobial susceptibility of Campylobacter isolates recovered from the preputial cavity of healthy rams in Turkey.

AIMS: Campylobacter sp. are important causes of reproductive disease in ruminants worldwide. Although healthy bulls are well-known carriers for infection of cows, the role of rams as a potential source for infecting ewes is unclear. This study aimed to determine prevalence, species distribution, genetic diversity and antimicrobial susceptibility profiles of Campylobacter sp. isolated from the preputial cavity of healthy rams. METHODS AND RESULTS: The material of this prospective study comprised 191 swab samples taken from the preputial cavity of healthy rams. Enrichment and membrane filtration were employed for the isolation of Campylobacter. Presumptive isolates were confirmed as Campylobacter by phenotypic and molecular tests. 16S rRNA gene sequence analysis was used for the definitive identification of the isolates at species level, and genotyping was performed using pulsed-field gel electrophoresis (PFGE). The susceptibility of the Campylobacter sp. isolates to various antibiotics was determined by the disk diffusion test. In all, 27 of the 191 (14·13%) swab samples were found to be positive for Campylobacter sp. (28 isolates were recovered in total). Per phenotypic and genotypic analyses, one isolate was identified as Campylobacter mucosalis and the remaining 27 isolates were identified as Campylobacter sputorum bv. faecalis. The PFGE analysis of the C. sputorum biovar faecalis isolates produced 17 clusters and 24 different pulsotypes, indicating high genetic heterogeneity. All 28 isolates were found to be susceptible to all of the antibiotics tested. CONCLUSIONS: Healthy rams may be an important reservoir of different Campylobacter species in the preputium. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated for the first time that healthy rams can carry different Campylobacter sp. including genetically diverse C. sputorum bv. faecalis and C. mucosalis in the preputial cavity. Further investigation on the potential implication of this finding on sheep reproductive health (e.g. infectious infertility, and abortion) and overall epidemiology of Campylobacter may be warranted.