CBP bromodomain could recognize acetylated lysine and function as transcription coactivator to regulate transcription and downstream gene expression. Furthermore, CBP has been shown to be related to many human malignancies including acute myeloid leukemia. Herein, we identified DC-CPin734 as a potent CBP bromodomain inhibitor with a TR-FRET IC50 value of 19.5 ± 1.1 nM and over 400-fold of selectivity against BRD4 bromodomains through structure based rational drug design guided iterative chemical modification endeavoring to discover optimal tail-substituted tetrahydroquinolin derivatives. Moreover, DC-CPin734 showed potent inhibitory activity to AML cell line MV4-11 with an IC50 value of 0.55 ± 0.04 μM, and its cellular on-target effects were further evidenced by c-Myc downregulation results. In summary, DC-CPin734 showing good potency, selectivity and anti AML activity could serve as a potent and selective in vitro and in vivo probe of CBP bromodomain and a promising lead compound for future drug development.This study reports a preparation of silver nanoparticles (SNPs) using Microsorum pteropus methanol extract, as a new approach in the development of therapeutic strategies against diseases caused by oxidative stress, reactive oxygen, and nitrogen species. During the effort of extraction and isolation from M. pteropus, X-ray single-crystal structural analysis of sucrose was succeeded. 1,1-Diphenyl-2-picrylhydrazyl (DPPH) and hydrogen peroxide scavenging assay were used to confirm the antioxidant potential. Preparation of SNPs was confirmed by ultraviolet-visible (UV-Vis) spectra with peaks between 431 and 436 nm. JSH-23 Infrared (IR) analysis showed OH, NH functional groups of alcohol, phenol, amine, and aliphatic CH stretching vibrations of hydrocarbon chains of the synthesized nanoparticles. The antioxidant properties of the SNPs significantly showed DPPH reduction with an IC₅₀ value of 47.0 µg/mL and hydrogen peroxide scavenging activity with an IC₅₀ value of 35.8 µg/mL, and hence, indicating their capability to eliminate potentially damaging oxidants involved in oxidative stress and their related diseases.The toxicological risk assessment of chemicals is largely based on the Organization for Economic Co-operation and Development (OECD) guidelines. These internationally approved methodologies help shape policy and political strategy of environment and human health issues. Risk assessments which pertain to soil biota ‘recruit’ sentinel organisms, including the earthworm Eisenia fetida. Despite E. fetida being morphologically similar to Dendrobaena veneta, they are characterized by a several-fold difference in sensitivity to xenobiotics. Worms, sold as either as pure E. fetida stocks or E. fetida/D. veneta mixed cultures, were obtained from five commercial suppliers. The species identity of 25 earthworms was determined by sequencing the cytochrome c oxidase subunit 2 (COII). We revealed that only one of 25 worms was E. fetida, the remaining worms were all identified as D. veneta. This underlines the notion that E. fetida and D. veneta are easily mis-identified. The occurrence of cryptic speciation combined with the well-documented species-specific variation in toxicological responses highlights the pressing need to accurately classify earthworms to species level prior to any toxicological research. Only this will ensure the validity and reliability of risk assessments.

To report long-term outcomes of primary deep sclerectomy (DS) in open-angle glaucoma (OAG) and identify factors influencing surgical failure and postoperative complications.

Retrospective cohort study.

Consecutive OAG patients undergoing primary DS with follow-up ≥1 year.

Three intraocular pressure (IOP) success cutoffs were defined ≤18 mmHg and 20% reduction, ≤15 mmHg and 25% reduction, and ≤12 mmHg and 30% reduction. Cox multivariable regression analysis investigated factors influencing failure and postoperative complications.

The primary outcome was the success rate of DS according to the defined criteria. Secondary outcomes included IOP over time; factors predictive of failure; incidence and predictive factors of serious post-operative complications.

513 eyes of 409 patients with a mean (±SD) age of 70.2 (±9.8) years and follow-up of 84.1 (±41.6) months. Mean (±SD) IOP decreased from 23.5 (±7.3) mmHg to 13.3 (±3.9), 12.8 (±4.3), 12.4 (±4.3) mmHg at 3, 5, and 7 years, respectively (p<0.001).ent phacoemulsification (p=0.007), and intraoperative bevacizumab (p=0.004), but not MMC (p=0.79), were associated with increased serious post-operative complications. For phakic patients, the estimated incidence (95% CI) of subsequent phacoemulsification was 16.4% (12.6-20.0%), 23.6% (19.2-27.8%), and 33.0% (27.7-38.0%) at 3, 5, and 7 years.

DS is an effective long-lasting primary surgical procedure for OAG.

DS is an effective long-lasting primary surgical procedure for OAG.Viral egress and autophagy are two mechanisms that seem to be strictly connected in Herpesviruses’s biology. Several data suggest that the autophagic machinery facilitates the egress of viral capsids and thus the production of new infectious particles. In the Herpesvirus family, viral nuclear egress is controlled and organized by a well conserved group of proteins named Nuclear Egress Complex (NEC). In the case of EBV, NEC is composed by BFRF1 and BFLF2 proteins, although the alterations of the nuclear host cell architecture are mainly driven by BFRF1, a multifunctional viral protein anchored to the inner nuclear membrane of the host cell. BFRF1 shares a peculiar distribution with several nuclear components and with them it strictly interacts. In this study, we investigated the possible role of BFRF1 in manipulating autophagy, pathway that possibly originates from nucleus, regulating the interplay between autophagy and viral egress.Mycobacterium avium complex is a causative organism for refractory diseases. In this study, we examined the effects of N-acetyl-cysteine on M. avium infection in vitro and in vivo. N-acetyl-cysteine treatment suppressed the growth of M. avium in A549 cells in a concentration-dependent manner. This effect was related to the induction of the antibacterial peptide human β-defensin-2. In a mouse model, N-acetyl-cysteine treatment significantly reduced the number of bacteria in the lungs and induced murine β-defensin-3. In interleukin-17-deficient mice, the effects of N-acetyl-cysteine disappeared, indicating that these mechanisms may be mediated by interleukin-17. Moreover, an additional reduction in bacterial load was observed in mice administered N-acetyl-cysteine in combination with clarithromycin. Our findings demonstrate the potent antimycobacterial effects of N-acetyl-cysteine against M. avium by inducing antimicrobial peptide, suggesting that N-acetyl-cysteine may have applications as an alternative to classical treatment regimens.