Angiogenesis and prostate cancer: MicroRNAs comes into view.

Angiogenesis, the formation of new blood vessels, is an important stage in the growth of cancer. Extracellular matrix, endothelial cells, and soluble substances must be carefully coordinated during the multistep procedure of angiogenesis. Inducers and inhibitors have been found to control pretty much every phase. In addition to benign prostatic hyperplasia, prostatic intraepithelial neoplasia, and angiogenesis have a critical role in the initiation and progression of prostate cancer. MicroRNA (miRNA) is endogenous, short, non-coding RNA molecules of almost 22 nucleotides play a role in regulating cellular processes and regulating several genes' expression. Through controlling endothelial migration, differentiation, death, and cell proliferation, miRNAs have a significant function in angiogenesis. A number of pathological and physiological processes, particularly prostate cancer's emergence, depend on the regulation of angiogenesis. Investigating the functions played with miRNAs in angiogenesis is crucial because it might result in the creation of novel prostate cancer therapies that entail regulating angiogenesis. The function of several miRNAs and its targeting genes engaged in cancer of the prostate angiogenesis will be reviewed in this review in light of the most recent developments. The potential clinical utility of miRNAs potentially a novel therapeutic targets will also be explored, as well as their capacity to control prostate cancer angiogenesis and the underlying mechanisms.

Efficiency of vanillin in impeding metabolic adaptability and virulence of Candida albicans by inhibiting glyoxylate cycle, morphogenesis, and biofilm formation.

BACKGROUND AND PURPOSE: Candida albicans is the fourth most common cause of nosocomial fungal infections across the world. The current drug regimens are suffering from such drawbacks as drug resistance, toxicity, and costliness; accordingly, they highlight the need for the discovery of novel drug agents. The metabolic adaptability under low-carbon conditions and expression of functional virulence traits mark the success of pathogens to cause infection. The metabolic pathways, such as glyoxylate cycle (GC), enable C. albicans to survive under glucose-deficient conditions prevalent in the hostile niche. Therefore, the key enzymes, namely isocitrate lyase (ICL) and malate synthase (MLS), represent attractive agents against C. albicans. Similarly, virulence traits, such as morphogenesis and biofilm formation, are the crucial determinants of C. albicans pathogenicity. Regarding this, the present study was conducted to uncover the role of vanillin (Van), a natural food flavoring agent, in inhibiting GC, yeast-to-hyphal transition, and biofilm formation in human fungal pathogen C. albicans. MATERIALS AND METHODS: For the determination of hypersensitivity under low-glucose conditions, phenotypic susceptibility assay was utilized. In addition, enzyme activities were estimated based on crude extracts while in-silico binding was confirmed by molecular docking. The assessment of morphogenesis was accomplished using hyphal-inducing media, and biofilm formation was estimated using calcofluor staining, MTT assay, and biomass measurement. Additionally, the in vivo efficacy of Van was demonstrated using Caenorhabditis elegans nematode model. RESULTS: Based on the results, Van was found to be a potent GC inhibitor that phenocopied ICL1 deletion mutant and displayed hypersensitivity under low-carbon conditions. Accordingly, Van facilitated the inhibition of ICL and MLS activities in vitro. Molecular docking analyses revealed the in-silico binding affinity of Van with Icl1p and Mls1p. Those analyses were also confirmative of the binding of Van to the active sites of both proteins with better binding energy in comparison to their known inhibitors. Furthermore, Van led to the attenuation of such virulence traits as morphogenesis, biofilm formation, and cell adherence. Finally, the antifungal efficacy of Van was demonstrated by the enhanced survival of C. elegans with Candida infection. The results also confirmed negligible hemolytic activity on erythrocytes. CONCLUSION: As the findings of the present study indicated, Van is a persuasive natural compound that warrants further attention to exploit its anticandidal potential.

Graft uptake rates with isoamyl-2-cyanoacrylate in myringoplasty procedures: a 10-year retrospective study.

OBJECTIVE: To assess graft uptake rates with the use of cyanoacrylate adhesives in myringoplasty procedures. STUDY DESIGN: Case series with chart review. Setting. Tertiary care center. SUBJECTS AND METHODS: Five hundred forty-two patients selected with safe central perforations were divided into 4 groups based on perforation size and each divided into 2 subgroups depending on the presence or absence of preexisting pathology on the remnant tympanic membrane. Myringoplasty without ossicular reconstruction was done postaurally or by transcanal approach, with inlay graft placed and adhesive applied. Ear pack was removed on the seventh postoperative day. Graft uptake rates, graft uptake time (neotympanum intact and mobile), and postoperative sequelae were noted. RESULTS: Graft uptake was about 99% at 3 months postsurgery. Residual perforation was seen in 2 patients in group 2 and 1 in group 4 and thinned-out tympanum in 1 patient in group 4. Mean uptake time was 21 days. Neotympanum mobility was sluggish in 9 cases postoperatively in group 4 and in 2 cases in group 3. Patients with successful (neotympanum intact and mobile) graft uptake showed significant improvement. Postoperative inflammatory signs in the external auditory canal were seen in 3 cases. CONCLUSION: Cyanoacrylate use in myringoplasty obtains graft uptake rates of 99% compared with most studies, which report 80% to 90%. This also allows removal of the pack by the seventh day, allowing close follow-up of the graft and less patient discomfort. Importantly, it has not interfered with the formation of the neotympanum or compromised hearing improvement.