Antimicrobial Susceptibility and Genetic Epidemiology of Extended-Spectrum β-Lactamase-Positive Enterobacterales Clinical Isolates in Central Poland.

The extended-spectrum β-lactamases (ESβLs) are bacterial enzymes capable of hydrolyzing penicillins, cephalosporins, and aztreonam. The prevalence of ESβL is increasing among clinically significant microorganisms worldwide, drastically reducing the therapeutic management of infectious diseases. The study aimed to determine the drug susceptibility of ESβL-positive clinical isolates acquired from patients hospitalized in Lodz, central Poland, and analyze the prevalence of specific genes, determining acquired resistance in these bacteria.

Cefiderocol - An effective antimicrobial for MDR infections but a challenge for routine antimicrobial susceptibility testing.

Purpose: Cefiderocol is a novel cephalosporin-siderophore conjugate antibiotic that holds promise to thwart infections caused by multi-drug-resistant gram-negative bacilli. Its antibacterial activity against normally susceptible species is not affected by most β-lactamases, including metallo-β-lactamases. Due to the siderophore-mediated entry into the cell, the activity of cefiderocol is less affected by porin loss or active efflux resistance than many other β-lactam antibiotics.

Tryptophan Metabolism in Postmenopausal Women with Functional Constipation.

Constipation belongs to conditions commonly reported by postmenopausal women, but the mechanism behind this association is not fully known. The aim of the present study was to determine the relationship between some metabolites of tryptophan (TRP) and the occurrence and severity of abdominal symptoms (Rome IV) in postmenopausal women with functional constipation (FC, n = 40) as compared with age-adjusted postmenopausal women without FC. All women controlled their TRP intake in their daily diet.

New -Adducts of Thiadiazole and Thiazoline with Levoglucosenone and Evaluation of Their Significant Cytotoxic (Anti-Cancer) Activity.

The conjugate N-adducts of thio-1,3,4-diazole and 2-thiazoline with levoglucosenone were synthesized via a stereoselective, base-catalyzed conjugate N-Michael addition to levoglucosenone at C-4. Structural assignments were established using 1H and 13C NMR analysis, and X-ray single-crystal analysis for one of the compounds. The biological properties of the novel compounds were tested on a cell model.

DNA Double-Strand Break Repair Inhibitors: YU238259, A12B4C3 and DDRI-18 Overcome the Cisplatin Resistance in Human Ovarian Cancer Cells, but Not under Hypoxia Conditions.

Cisplatin (CDDP) is the cornerstone of standard treatment for ovarian cancer. However, the resistance of ovarian cancer cells to CDDP leads to an inevitable recurrence. One of the strategies to overcome resistance to CDDP is the combined treatment of ovarian cancer with CDDP and etoposide (VP-16), although this strategy is not always effective.

In Vitro Activity of Eravacycline against Carbapenemase-Producing Gram-Negative Bacilli Clinical Isolates in Central Poland.

Eravacycline is a novel antibiotic of the tetracycline class with activity against a broad spectrum of clinically significant bacteria, including multi-drug-resistant organisms. For this reason, it may be an alternative to treating critical infections of this etiology. We aimed to assess the in vitro effectiveness of eravacycline to carbapenemase-producing Gram-negative bacilli clinical isolates identified in hospitals in Łódź, Poland.

Carbapenem-Resistant Gram-Negative Fermenting and Non-Fermenting Rods Isolated from Hospital Patients in Poland-What Are They Susceptible to?

Gram-negative fermenting and non-fermenting bacteria are important etiological factors of nosocomial and community infections, especially those that produce carbapenemases. , and are the most frequently-detected carbapenemase-producing microorganisms. The predominant type of resistance is metallo-β-lactamase (MBL).

Responses of human colon and breast adenocarcinoma cell lines (LoVo, MCF7) and non-tumorigenic mammary epithelial cells (MCF-10A) to the acellular fraction of packed red blood cells in the presence and absence of cisplatin.

Perioperative blood transfusion in colorectal and some other cancer patients has been linked to the increased risk for recurrence, but a causal mechanism remains unclear. During the preparation and storage of packed red blood cells (PRBCs) bio-active substances accumulate in the acellular fraction (supernatant). Viability, proliferation, reactive oxygen species (ROS) levels, and DNA damage of colon (LoVo) and breast (MCF7) adenocarcinoma cells and non-tumorigenic MCF-10A cell line were determined in response to the supernatants of fresh and long-stored (day 42) PRBCs, leukoreduced (LR) or non-leukoreduced (NLR).

Packed Red Blood Cell Supernatants Do Not Promote Growth or Cisplatin Resistance of Myeloid Leukemia K-562 Cells.

Background: A decreased immune surveillance as a consequence of packed red blood cell (PRBC) transfusions has been linked to cancer recurrence and progression, but a causal mechanism remains unclear. During processing and storage of PRBC, numerous bioactive substances accumulate in the acellular fraction (supernatant) of PRBC.

Aim: The study aimed to determine whether the supernatant of leukocyte-reduced (LR) and non-leukocyte-reduced (NLR) long-stored PRBC can modulate the survival and proliferation of myeloid leukemia K-562 cells, and the influence of cisplatin (cisPt) on these processes.

DNA double-strand breaks repair inhibitors potentiates the combined effect of VP-16 and CDDP in human colorectal adenocarcinoma (LoVo) cells.

Unlabelled: I.

Background: A combination of etoposide (VP-16) and cisplatin (CDDP) is the standard treatment for certain colon cancers. These drugs promote the death of cancer cells via direct and indirect induction of the most lethal DNA lesions - DNA double-stand breaks.

Polyphenolic-polysaccharide conjugates from medicinal plants of Rosaceae/Asteraceae family protect human lymphocytes but not myeloid leukemia K562 cells against radiation-induced death.

The aim of the study was to investigate whether the polyphenolic-polysaccharide conjugates (PPCs), isolated from flowers of Sanguisorba officinalis L. and Erigeron canadensis L., and from leaves of Fragaria vesca L.

Inhibition of DNA-PK potentiates the synergistic effect of NK314 and etoposide combination on human glioblastoma cells.

Etoposide (VP-16) is the topoisomerase 2 (Top2) inhibitor used for treating of glioma patients however at high dose with serious side effects. It induces DNA double-strand breaks (DSBs). These DNA lesions are repaired by non-homologous DNA end joining (NHEJ) mediated by DNA-dependent protein kinase (DNA-PK).

Comparison of the effect of three different topoisomerase II inhibitors combined with cisplatin in human glioblastoma cells sensitized with double strand break repair inhibitors.

Topoisomerase II (Topo2) inhibitors in combination with cisplatin represent a common treatment modality used for glioma patients. The main mechanism of their action involves induction of DNA double-strand breaks (DSBs). DSBs are repaired via the homology-dependent DNA repair (HRR) and non-homologous end-joining (NHEJ).

DNA Double Strand Breaks Repair Inhibitors: Relevance as Potential New Anticancer Therapeutics.

DNA double-strand breaks are considered one of the most lethal forms of DNA damage. Many effective anticancer therapeutic approaches used chemical and physical methods to generate DNA double-strand breaks in the cancer cells. They include: IR and drugs which mimetic its action, topoisomerase poisons, some alkylating agents or drugs which affected DNA replication process.

Thio-functionalized carbohydrate thiosemicarbazones and evaluation of their anticancer activity.

Thiosemicarbazides and their analogs have shown potential medical applications as antiviral, antibacterial and anticancer drugs. We designed, synthesized and evaluated in vitro anticancer activity against ovarian (A2780), cervix (HeLa), colon (LoVo), breast (MCF-7) and brain (MO59J) human cancer cell lines of seven novel compounds -S-glycosylated thiosemicarbazones. We assessed the cyto- and genotoxic properties of all novel compounds using a variety of methods including comet assay, XTT assay, various fluorescent assays and toxicology PathwayFinder expression array.

The induction of oxidative stress in cervix carcinoma cells by levoglucosenone derived 4-S-salicyl derivative and (1-4)-S-thio-disaccharides. Part 4.

(1-4)-S-thiodisaccharides were shown to kill various cancer cell lines, including cervix, lung, mammary-gland and colon by unknown mechanisms. Here we identified two actions of levoglucosenone derived (1-4)-S-thiodisaccharides against cervix cancer cells: induction of oxidative stress and DNA damage. In consequence, (1-4)-S-thiodisaccharides lowered the cellular GSH level and changed the expression profile of genes encoding key proteins involved with oxidative stress response.

The oxidative induction of DNA lesions in cancer cells by 5-thio-d-glucose and 6-thio-d-fructopyranose and their genotoxic effects. Part 3.

Thio-sugars have been described as potent inhibitors of cancer cell growth but the detailed mechanism of action remains unknown. Herein we investigated the mechanism of their anticancer action in the HeLa cell line. We investigated two thio-sugars: 5-thio-d-glucose (FCP1) and 6-thio-β-d-fructopyranose (FCP2).

Polymorphisms in microRNA target sites modulate risk of lymphoblastic and myeloid leukemias and affect microRNA binding.

Background: MicroRNA dysregulation is a common event in leukemia. Polymorphisms in microRNA-binding sites (miRSNPs) in target genes may alter the strength of microRNA interaction with target transcripts thereby affecting protein levels. In this study we aimed at identifying miRSNPs associated with leukemia risk and assessing impact of these miRSNPs on miRNA binding to target transcripts.