Modified Peptide Molecules As Potential Modulators of Shelterin Protein Functions; TRF1.

In this work, we present studies on relatively new and still not well-explored potential anticancer targets which are shelterin proteins, in particular the TRF1 protein can be blocked by in silico designed "peptidomimetic" molecules. TRF1 interacts directly with the TIN2 protein, and this protein-protein interaction is crucial for the proper functioning of telomere, which could be blocked by our novel modified peptide molecules. Our chemotherapeutic approach is based on assumption that modulation of TRF1-TIN2 interaction may be more harmful for cancer cells as cancer telomeres are more fragile than in normal cells. We have shown in vitro within SPR experiments that our modified peptide PEP1 molecule interacts with TRF1, presumably at the site originally occupied by the TIN2 protein. Disturbance of the shelterin complex by studied molecule may not in short term lead to cytotoxic effects, however blocking TRF1-TIN2 resulted in cellular senescence in cellular breast cancer lines used as a cancer model. Thus, our compounds appeared useful as starting model compounds for precise blockage of TRF proteins.

Combined anticancer therapy with imidazoacridinone analogue C-1305 and paclitaxel in human lung and colon cancer xenografts-Modulation of tumour angiogenesis.

The acridanone derivative 5-dimethylaminopropylamino-8-hydroxytriazoloacridinone (C-1305) has been described as a potent inhibitor of cancer cell growth. Its mechanism of action in in vitro conditions was attributed, among others, to its ability to bind and stabilize the microtubule network and subsequently exhibit its tumour-suppressive effects in synergy with paclitaxel (PTX). Therefore, the objective of the present study was to analyse the effects of the combined treatment of C-1305 and PTX in vivo. In addition, considering the results of previous genomic analyses, particular attention was given to the effects of this treatment on tumour angiogenesis. Treatment with C-1305 revealed antitumor effect in A549 lung cancer cells, and combined treatment with PTX showed tendency to anticancer activity in HCT116 colon cancer xenografts. It also improved tumour blood perfusion in both tumour models. The plasma level of CCL2 was increased and that of PDGF was decreased after combined treatment with C-1305 and PTX. The experimental results showed that the levels of FGF1, TGF-ß and Ang-4 decreased, whereas the levels of ERK1/2 and Akt phosphorylation increased in HCT116 tumour tissue following combined treatment with both drugs. The results of in vitro capillary-like structure formation assay demonstrated the inhibiting effect of C-1305 on this process. Although previous in vitro and in vivo studies suggested a positive effect of C-1305 on cancer cells, combined treatment of HCT116 human colon and A549 lung cancer cells with both PTX and C-1305 in vivo showed that the antitumor activity was restricted and associated with the modulation of tumour angiogenesis.

Protecting Breastfeeding during the COVID-19 Pandemic: A Scoping Review of Perinatal Care Recommendations in the Context of Maternal and Child Well-Being.

The objective of this scoping review is to determine to what extent the recommendations on perinatal care protect breastfeeding during the COVID-19 pandemic. The review follows the PRISMA ScR Extension guidelines. The research was conducted in Scopus, Medline via Pubmed, and Web of Science databases from 1 March 2020 to 31 May 2021, using 392 combinations of keywords. We searched for reviews and original papers published in English providing recommendations on delivery mode, companion during labor, the possibility of skin-to-skin contact (SSC), breastfeeding, and visitors policy. After screening, 86 out of 8416 publications qualified for data extraction. The majority of them indicated that COVID-19 infection is not a sufficient reason for a cesarean section; however, on a national level, cesarean births in severely ill patients were overrepresented. A significant number of recommendations deprived mothers of the necessary support during their labor and stay in the maternity ward. A shared decision-making model was hardly visible. Only the earliest COVID-19 recommendations suspended direct breastfeeding; in later publications, decisions were related to the mother's health, but other options of natural feeding were rarely discussed.

[Bacterial flora of conjunctival sac in patients with cataract. Methods of disinfection and evaluation of their efficiency]. / Mikroflora worka spojówkowego u chorych z zacma--metody dezynfekcji i ocena ich skutecznosci.

PURPOSE: 1) To evaluate the microbacterial flora of the conjunctival sac and the sensitivity of the isolated microorganisms to 0.3% gentamicin solution and 5.0% PVP-Jodi solution, which is used to disinfect conjunctival sac. 2) To evaluate the role of the adhesive foil in prevention of the infection of the operative field. MATERIAL AND METHODS: 170 patients with senile cataract were examined. Before admission to Ophthalmology Department each patient received 0.3% gentamicin solution three times a day. All patients had their conjunctival sac disinfected with the use of 5% PVP-Jodi before surgery. Patients were divided into two groups. In the first group (120 patients), first samples were taken on admission to the Ophthalmology Department. Next in the day of the procedure, in the operation room--first before and second after disinfection of conjunctival sac. Adhesive foil was not used in this group. In the second group (50 patients), we used adhesive foil before surgery and samples were taken before and after disinfection of conjunctival sac. RESULTS: On admission, positive cultures were obtained in 40.0% cases. Most of the bacterial flora were Gram-positive bacteria. The number of the positive cultures before disinfection with 5.0% PVP-Jodi solution diminished to 5.8%, compared with positive results obtained on admission to the Ophthalmology Department. Secondary infection of the conjunctival sac has been revealed in 10% after disinfection with the use of the 5.0% PVP Jodi. It was due to bacterial flora coming from the skin and limbs of the lids (in the group without adhesive foil), whereas positive samples were obtained in 2.0% in the group where adhesive foil was used. CONCLUSIONS: 1) Gentamicin significantly reduces the amount of bacterial flora in conjunctival sac in patients before cataract surgery. 2) Adhesive foil is efficient to protect operative field from infection.

[Bacteriological contents of conjunctival sac in patients with cataract in the early post-operative period]. / Bakteriologiczna zawartosc worka spojówkowego u pacjentów z zacma we wczesnym okresie pooperacyjnym.

PURPOSE: Evaluation of conjunctival microflora in patients with cataract, during the early post-operative period. MATERIAL AND METHODS: One hundred twenty patients scheduled for cataract extraction were evaluated. In each patient, conjunctival swab was taken directly after cataract surgery and two to three days postoperatively. Following surgical procedure all patients received topical antibiotics alone or along with steroids. The agents were placed into conjunctival sac of the operated eye. Ophthalmic ointments were administered HS and eye drops QID. RESULTS: 9.2% (11 patients) of the cultures of conjunctival swabs collected right after surgical procedure were positive for growth with predominantly Gram-positive organisms, mainly Staphyloccocus spp. These, were compared with 24.2% (29 patients) of positive cultures from conjunctival swabs collected two to three days later. 4.2% of the latter were also positive when taken in the operating room, immediately after a surgical procedure. The remaining 20.0% of positive cultures swabbed two to three days after surgery were resulted from the contamination of conjunctival sac with germs during the postoperative hospitalisation. CONCLUSIONS: There is a risk of early post-operative infection in patients undergoing cataract surgery. It is caused by the appearance of microflora in the conjunctival sac.