Ozone-based eye drops activity on ocular epithelial cells and potential pathogens infecting the front of the eye

Confirmation of the biological effectiveness of new ophthalmic preparations introduced in the market is an important element in maintaining the safety of using this type of medications. This study aimed to investigate the activity of Ozodrop® on human corneal and conjunctival epithelial cells, as well as its antibacterial and antifungal activity. Cytotoxicity analyses of ocular surface epithelial cells were performed in vitro by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) and Neutral Red uptake assays. The level of nitric oxide released by the cells was assessed by the Griess method. The reduction of the DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical by the tested formulation was analyzed. Microbiological tests were also performed. It was found that the Ozodrop® preparation exhibited biological activity, but was less active than the reference antibiotics and the anti-yeast agent. The cytotoxic activity of the Ozodrop® formulation was dependent on the time of cell exposure to it. No toxic effect was observed in the short-term, for up to 3 h. It appeared after 24 h of exposure of the cells to the preparation. The drops showed antioxidant activity in the specified concentration range. They also stimulated the release of nitric oxide, mainly by corneal epithelial cells. The Ozodrop® formulation exhibits biological activity that can be considered useful in the treatment of infections in the front part of the eye

Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial

Objective: Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents. Methods: In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/>100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients. Results: More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p<0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p<0.001), ACR50 (p≤0.05) and PASI75 (p<0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change −0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change −0.13). No unexpected adverse events were observed through week 60. Conclusions: The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients

Promoter repression and 3D-restructuring resolves divergent developmental gene expression in TADs

Cohesin loop extrusion facilitates precise gene expression by continuously driving promoters to sample all enhancers located within the same topologically-associated domain (TAD). However, many TADs contain multiple genes with divergent expression patterns, thereby indicating additional forces further refine how enhancer activities are utilised. Here, we unravel the mechanisms enabling a new gene, Rex1, to emerge with divergent expression within the ancient Fat1 TAD in placental mammals. We show that such divergent expression is not determined by a strict enhancer-promoter compatibility code, intra-TAD position or nuclear envelope-attachment. Instead, TAD-restructuring in embryonic stem cells (ESCs) separates Rex1 and Fat1 with distinct proximal enhancers that independently drive their expression. By contrast, in later embryonic tissues, DNA methylation renders the inactive Rex1 promoter profoundly unresponsive to Fat1 enhancers within the intact TAD. Combined, these features adapted an ancient regulatory landscape during evolution to support two entirely independent Rex1 and Fat1 expression programs. Thus, rather than operating only as rigid blocks of co-regulated genes, TAD-regulatory landscapes can orchestrate complex divergent expression patterns in evolution

The ribonuclease DIS3 promotes let-7 miRNA maturation by degrading the pluripotency factor LIN28B mRNA

Multiple myeloma, the second most frequent hematologic tumor after lymphomas, is an incurable cancer. Recent sequencing efforts have identified the ribonuclease DIS3 as one of the most frequently mutated genes in this disease. DIS3 represents the catalytic subunit of the exosome, a macromolecular complex central to the processing, maturation and surveillance of various RNAs. miRNAs are an evolutionarily conserved class of small noncoding RNAs, regulating gene expression at post-transcriptional level. Ribonucleases, including Drosha, Dicer and XRN2, are involved in the processing and stability of miRNAs. However, the role of DIS3 on the regulation of miRNAs remains largely unknown. Here we found that DIS3 regulates the levels of the tumor suppressor let-7 miRNAs without affecting other miRNA families. DIS3 facilitates the maturation of let-7 miRNAs by reducing in the cytoplasm the RNA stability of the pluripotency factor LIN28B, a inhibitor of let-7 processing. DIS3 inactivation, through the increase of LIN28B and the reduction of mature let-7, enhances the translation of let-7 targets such as MYC and RAS leading to enhanced tumorigenesis. Our study establishes that the ribonuclease DIS3, targeting LIN28B, sustains the maturation of let-7 miRNAs and suggests the increased translation of critical oncogenes as one of the biological outcomes of DIS3 inactivation

Actin cytoskeleton in the extra-ovular embryo sac of Utricularia nelumbifolia (Lentibulariaceae)

The actin cytoskeleton in the mature female gametophyte of angiosperms has been examined in only a few dicot and monocot species. The main purposes of this study were to identify how the actin cytoskeleton is arranged in the mature extra-ovular embryo sac in Utricularia nelumbifolia (Lentibulariaceae). We found that the extra-ovular part of the central cell has a well-developed actin cytoskeleton: actin microfilaments formed of long strands which run longitudinally or transversally to the long axis of the embryo sac. The exerted part of the central cell, which is exposed to the environment of the ovary chamber, is highly vacuolated and in the thin peripheral cytoplasm possesses a complicated network of actin microfilaments. The epidermal cells of the placenta that are in contact with the extra-ovular part of the embryo sac are crushed. The ultrastructure data of these cells are presented. We detected the accumulation of the actin cytoskeleton between the micropylar parts of the synergids and the extra-ovular part of central cell. This actin accumulation is unusual because in typical angiosperms the micropylar parts of the synergids form the apex of the female gametophyte

Defects detection in the natural leathers using linear infrared lamp

W artykule przedstawiono wyniki badań nieniszczących nad opracowywaną metodą wykrywania defektów naruszających jednorodną strukturą budowy wewnętrznej i zewnętrznej wygarbowanych skór naturalnych, zwłaszcza licowych. W prezentowanej metodzie użyto liniowego promiennika podczerwieni do osiągnicia wymuszenia temperatury o charakterze impulsowym. Do pomiaru rozkładu temperatury na powierzchni badanej, w eksperymencie użyto kamery termowizyjnej. W badaniach zaproponowano opracowany algorytm przetwarzający pakiet termogramów zarejestrowanych w czasie ochładzania powierzchni badanej skóry. Przedstawiono wybrane wyniki badań eksperymentalnych oraz wyniki działania opracowywanego algorytmu wykrywania defektów w skórach. Osiągnięto zadowalające wyniki badań.The paper deals with a method of detecting defects of uniform internal and external structure of tanned natural leather, especially grain leather. These defects can result from damages of the leather originated during an animal lifetime or later during the tanning and finishing process. In the presented method a linear infrared lamp was used to obtain the impulse heat input. The temperature response on the examined leather surface was measured using an infrared camera. The series of thermograms recorded during the leather cooling were processed using the developed algorithm. Selected r esults of experiments illustrating the performance of the processing algorithm are presented in the paper. The results obtained in the tests were satisfactory. Computations were carried out in the Matlab software environment. The presented solution is a part of a project whose goal is to design an industry device for non destructive testing and detecting structure defects in natural leather used in the furniture upholstery