Aging deteriorates quality of sperm produced by male mice with partial Yq deletion

The aim of the study was to assess the cumulative effects of aging and Y-chromosome long arm deletion on sperm quality parameters. Motility, mitochondrial activity, and head morphology were evaluated for sperm of 3- and 12-month-old males from B10.BR-Y^del and B10.BR congenic mouse strains. The study revealed that quality and fertilizing potential of sperm produced by younger and older B10.BR males persist on similar levels, but worsen significantly with age of B10.BR-Y^del males. The findings imply that partial Yq deletions might be more harmful for spermiogenesis in advancing age and may be applicable to other species including humans.

Abbreviations: AZF: azoospermia factor; MSYq: male-specific region of the Y-chromosome long arm     

The Impact of Dietary Polyphenols on COX-2 Expression in Colorectal Cancer

Polyphenols are natural compounds with high structural diversity whose common occurrence in plants renders them intrinsic dietary components. They are known to be secondary metabolites characterized by a wide spectrum of biological activities, and a growing body of evidence indicates they have anti-inflammatory potential. It is well known that inflammation plays a key role in many chronic diseases such as circulatory diseases, pulmonary diseases, autoimmune diseases, diabetes, cancer, and neurodegenerative diseases.

Polyphenols influence the inflammatory process by controlling and inhibiting pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, and TNF-α, and cyclooxygenase-2 (COX-2) enzyme involved in the metabolism of arachidonic acid. Furthermore, polyphenols exhibit anti-inflammatory activity on many levels via NF-κB inhibition, and MAPK, iNOS, and growth factors regulation. This paper reviews the current state of knowledge concerning the potential of various dietary polyphenols to inhibit the effects of COX-2 in colon cancer, by examining the available evidence regarding the efficacy and safety of these compounds obtained from in vitro and animal studies.     

Effects of exposure to 5-MeO-DIPT during adolescence on brain neurotransmission and neurotoxicity in adult rats

Forensic Toxicology - Tryptamine hallucinogen 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) is a serotonin transporter inhibitor with high affinity for serotonin 5-HT1A and 5-HT2A/C receptors....     

Correlations between Low Doses of Zearalenone,Its Carryover Factor and Estrogen Receptor Expression in Different Segments of the Intestines in Pre-Pubertal Gilts—A Study Protocol

Plant materials can be contaminated with Fusarium mycotoxins and their derivatives, whose toxic effects on humans and animals may remain subclinical. Zearalenone (ZEN), a low-molecular-weight compound, is produced by molds in crop plants as a secondary metabolite. The objective of this study will be to analyze the in vivo correlations between very low monotonic doses of ZEN (5, 10, and 15 μg ZEN/kg body weight—BW for 42 days) and the carryover of this mycotoxin and its selected metabolites from the intestinal contents to the intestinal walls, the mRNA expression of estrogen receptor alfa (ERα) and estrogen receptor beta (ERβ) genes, and the mRNA expression of genes modulating selected colon enzymes (CYP1A1 and GSTP1) in the intestinal mucosa of pre-pubertal gilts. An in vivo experiment will be performed on 60 clinically healthy animals with initial BW of 14.5 ± 2 kg. The gilts will be randomly divided into a control group (group C, n = 15) and three experimental groups (group ZEN5, group ZEN10, and group ZEN15; n = 15). Group ZEN5 will be administered per os 5 μg ZEN/kg BW (MABEL), group ZEN10—10 μg ZEN/kg BW (NOAEL), and group ZEN15—15 µg ZEN/kg BW (low LOAEL). In each group, five animals will be euthanized on analytical dates 1 (exposure day 7), 2 (exposure day 21), and 3 (exposure day 42). Samples for in vitro analyses will be collected from an intestinal segment resected from the following regions: the third (horizontal) part of the duodenum, jejunum, ileum, cecum, ascending colon, transverse colon, and descending colon. The experimental material will be collected under special conditions, and it will be transported to specialist laboratories where samples will be obtained for further analyses.     

Design,Synthesis, and Biological Evaluation of Imidazopyridines as PD-1/PD-L1 Antagonists

The PD-1/PD-L1 axis has proven to be a highly efficacious target for cancer immune checkpoint therapy with several approved antibodies. Also, small molecules based on a biphenyl core can antagonize PD-1/PD-L1, leading to the in vitro formation of PD-L1 dimers. However, their development remains challenging, as we do not yet fully understand their mode of action. In this work, we designed a new scaffold based on our previously solved high-resolution structures of low-molecular-weight inhibitors bound to PD-L1. A small compound library was synthesized using the Groebke–Blackburn–Bienaymé multicomponent reaction (GBB-3CR), resulting in the structure–activity relationship of imidazo[1,2-a]pyridine-based inhibitors. These inhibitors were tested for their biological activity using various biophysical assays giving potent candidates with low-micromolar PD-L1 affinities. An obtained PD-L1 cocrystal structure reveals the binding to PD-L1. Our results open the door to an interesting bioactive scaffold that could lead to a new class of PD-L1 antagonists.     

Effects of kinesio taping on anaerobic power recovery after eccentric exercise

The aim of the study was to evaluate the effectiveness of kinesio taping (KT) in anaerobic power recovery after eccentric exercise. The study was carried out on 10 healthy men. The participants performed two 60-min downhill runs with a constant intensity. Peak anaerobic power (PP) and mean power (MP) were measured before and five times after eccentric exercise. Anaerobic power was evaluated with the Maximal Cycling Sprint Test. After the downhill run, passive recovery (PR) and KT (lymphatic application) were applied in random order. A significant decrease in PP and MP was observed at least for 24 h after PR, compared to baseline. After the KT application 24 h after eccentric exercises, anaerobic power was already similar to the baseline measurement. The application of KT significantly improved anaerobic power recovery time after eccentric exercise compared to the period of passive rest immediately prior to testing.     

Novel Piperazine Arylideneimidazolones Inhibit the AcrAB-TolC Pump in Escherichia coli and Simultaneously Act as Fluorescent Membrane Probes in a Combined Real-Time Influx and Efflux Assay

In this study, we tested five compounds belonging to a novel series of piperazine arylideneimidazolones for the ability to inhibit the AcrAB-TolC efflux pump. The biphenylmethylene derivative (BM-19) and the fluorenylmethylene derivative (BM-38) were found to possess the strongest efflux pump inhibitor (EPI) activities in the AcrAB-TolC-overproducing Escherichia coli strain 3-AG100, whereas BM-9, BM-27, and BM-36 had no activity at concentrations of up to 50 μM in a Nile red efflux assay. MIC microdilution assays demonstrated that BM-19 at 1/4 MIC (intrinsic MIC, 200 μM) was able to reduce the MICs of levofloxacin, oxacillin, linezolid, and clarithromycin 8-fold. BM-38 at 1/4 MIC (intrinsic MIC, 100 μM) was able to reduce only the MICs of oxacillin and linezolid (2-fold). Both compounds markedly reduced the MIC of rifampin (BM-19, 32-fold; and BM-38, 4-fold), which is suggestive of permeabilization of the outer membrane as an additional mechanism of action. Nitrocefin hydrolysis assays demonstrated that in addition to their EPI activity, both compounds were in fact weak permeabilizers of the outer membrane. Moreover, it was found that BM-19, BM-27, BM-36, and BM-38 acted as near-infrared-emitting fluorescent membrane probes, which allowed for their use in a combined influx and efflux assay and thus for tracking of the transport of an EPI across the outer membrane by an efflux pump in real time. The EPIs BM-38 and BM-19 displayed the most rapid influx of all compounds, whereas BM-27, which did not act as an EPI, showed the slowest influx.