Continuous development of personalized treatments is undoubtedly beneficial for oncogenic patients’ comfort and survival rate. Mutant TP53 is associated with a worse prognosis due to the occurrence ...of metastases, increased chemoresistance, and tumor growth. Currently, numerous compounds capable of p53 reactivation or the destabilization of mutant p53 are being investigated. Several of them, APR-246, COTI-2, SAHA, and PEITC, were approved for clinical trials. This review focuses on these novel therapeutic opportunities, their mechanisms of action, and their significance for potential medical application.
The COVID-19 pandemic outbreak led to a global ventilator shortage. Hence, various strategies for using a single ventilator to support multiple patients have been considered. A device called Ventil ...previously validated for independent lung ventilation was used in this study to evaluate its usability for shared ventilation. We performed experiments with a total number of 16 animals. Eight pairs of pigs were ventilated by a ventilator or anesthetic machine and by Ventil for up to 27 h. In one experiment, 200 ml of saline was introduced to one subject's lungs to reduce their compliance. The experiments were analyzed in terms of arterial blood gases and respiratory parameters. In addition to the animal study, we performed a series of laboratory experiments with artificial lungs (ALs). The resistance and compliance of one AL (affected) were altered, while the tidal volume (TV) and peak pressure (Ppeak) in the second (unaffected) AL were analyzed. In addition, to assess the risk of transmission of pathogens between AL respiratory tracts, laboratory tests were performed using phantoms of virus particles. The physiological level of analyzed parameters in ventilated animals was maintained, except for CO
tension, for which a permissive hypercapnia was indicated. Experiments did not lead to injuries in the animal's lungs except for one subject, as indicated by CT scan analysis. In laboratory experiments, changes in TV and Ppeak in the unaffected AL were less than 11%, except for 2 cases where the TV change was 20%. No cross-contamination was found in simulations of pathogen transmission. We conclude that ventilation using Ventil can be considered safe in patients undergoing deep sedation without spontaneous breathing efforts.
The study aimed to examine samples of different market original sheep cow and goat cheeses, in respect of the content and profile of FA with special emphasis on health-promoting FA. The content of ...fatty acids in the examined cheeses was highly differentiated and depended on the sort and type of cheese. The content of fatty acid groups in milk fat varied within the limits: SFA, 55.2-67.2%; SCSFA, 10.9-23.4%; BCFA, 1.6-2.9%; MUFA, 15.2-23.4%; PUFA, 1.9-4.3%;
-MUFA, 1.8-6.0%; and CLA, 1.0-3.1%. From among the examined cheeses, the seasonal sheep cheeses (Oscypek) and mountain cow cheeses were characterized by the highest content of health-promoting fatty acids. The content of health-promoting fatty acids in the fat fraction of these cheeses was CLA 2.1-3.1%,
-MUFA 3.5-6%, BCFA 2.7-2.9%, and SCSFA 12-18%.
The paradigm is gradually shifting, with radiosurgery and endovascular embolization being increasingly chosen over surgical resection in the selected cases of brain arteriovenous malformations. ...Routinely used X-ray monitoring of liquid embolic infusion has very good spatial and temporal resolution but is not without significant drawbacks regarding poor visualization of the complex AVM angioarchitecture, especially after many embolizations in the past and therefore limiting the technical ability of the embocure-total occlusion of the feeding arteries, nidus, and draining veins. The purpose of this study was to evaluate the use of real-time MRI guidance in endovascular embolization with Onyx (instead of X-ray) in a single swine rete mirabile (RM) AVM model in order to provide the scaffolding for the real-time MRI guidance method. Onyx propagation was observed in real-time dynamic GE-EPI scan with initial ipsilateral RM filling followed by main cerebral arterial branch distribution. The relatively bright signal within RM and the brain prior to Onyx injection provided a good background for the dark, low signal of the embolic agent spreading in rete mirabile and brain arteries. X-ray picture confirmed Onyx cast distribution at the end of the procedure. In this initial experience, real-time MRI seems to be a promising method that may significantly improve liquid embolic agent infusion monitoring in the future, although requiring further development before clinical use.
Uterine myoactivity is crucial for successful reproductive performance of the sow. Spontaneous contractions of the uterus are strictly controlled and coordinated. Uterine electromyographic (EMG) ...activity undergoes hormonal regulation with rapid and long-term effects. What is more, interstitial Cajal-like Cells (ICLC) appear essential for smooth muscle contractility in the reproductive tract where they are suspected to be playing a major role in generating, coordinating, modulating and synchronizing slow triggering waves. The aim of this study was to investigate the myoelectrical activity of sow's uterus during estrus cycle.
Study was conducted on 10 Polish Landrace sows. Propagation mechanisms and their connection with the uterine EMG activity were considered in correlation with expression of c-kit, progesterone and oxytocin receptors of the non-pregnant sow. ICLC were labeled with antibody directed against c-kit receptor and visualized by confocal microscopy and scanning cytometer for positive cells percentage assessment. EMG signal was recorded directly from the myometrium with telemetry transmitters and electrodes located in different topographic regions of reproductive tracts. The stages of estrus cycle were determined by monitoring levels of luteinizing hormone, progesterone and estrogen with radioimmunoassays. Significant differences of the EMG signal parameters between diestrus and estrus and the correlations with density of labelled receptors were demonstrated. Moreover, the electrophysiological studies indicated that ICLC in the myometrium in the tip of uterine horn may participate in the regulation of slow waves duration and frequency.
The pattern of EMG signal propagation in the wall of the non-pregnant porcine uterus occurs in an orderly, bidirectional fashion and at distinctive speed, with no differences between diestrus and estrus.
The weaning period in piglets draws significant attention from researchers, veterinarians, and breeders. A substantial change in diet accompanied by enormous stress has health and welfare ...implications (abnormal feeding intake, infections, umbilical lesions, etc.). While the parameters like optimal age or weight for the weaning have been studied extensively, relatively less attention has been devoted to the study of stress effects in the piglets' biochemistry. As one of the effects of stress is hyperventilation, a gasometric analysis supported by measurements of hypoxia biomarkers was conducted. Piglets blood and urine, one day and seven days before and one day and seven days after the weaning, were tested. There was no evidence of hyperventilation, but phosphaturia and hypophosphatemia were observed one and seven days postweaning, respectively. A statistical analysis across the population also pointed to minor tissue hypoxia. Our work contributes to an understanding of biochemical dynamics and helps in the interpretation of physiological changes observed in piglets in this critical period.
Intrauterine growth restricted (IUGR) piglets are born at term but have low birth mass and a characteristic shape of the head. Impaired general condition, especially in intestinal function, leads to ...an increase in the occurrence of diarrhoea and high mortality in the first days of life. So far, the mechanical and immunological gut barrier functions in IUGR are poorly understood. The aim of this study was to microscopically evaluate the early postnatal changes in the gut mucosa occurring in IUGR piglets. Whole-tissue small intestine samples were collected from littermate pairs (IUGR and normal) on postnatal day (PD) 7, 14 and 180 and analysed by light microscopy. We found that in the IUGR piglets, the percentage of intraepithelial leukocytes was reduced in the duodenum on PD 7, but it increased in the proximal and middle jejunum both on PD 7 and PD 14, which suggested the development of an inflammatory process. The number of goblet cells was also reduced on PD 14. The average size of the Peyer's patches in the distal jejunum and ileum showed significant reduction on PD 7 as compared to normal pigs; however, on PD 14, it returned to normal. On PD 180, we did not find any differences in the measured parameters between the IUGR and the normal pigs. In conclusion, we found that in one-week-old IUGR pig neonates, the gut barrier and the immune system structures display signs of retarded development but recover within the second postnatal week of life.
Intrauterine growth restricted (IUGR) pigs are characterized by high perinatal mortality and dysfunction of internal organs, adipose, and muscle tissues. However, little is known about the ...post-weaning performance and meat quality of the IUGR pigs. The aim of this study was to compare normal pigs and pigs with IUGR from birth until slaughter, also with respect to their meat quality. Pigs with the IUGR achieved lower slaughter weight but did not differ significantly from normal pigs in terms of their meat content. The IUGR did not negatively affect the culinary quality of the obtained meat, including its content of basic chemical components and energy value, as well as hardness, chewiness, cohesiveness, elasticity, and penetration force. The meat of the IUGR pigs, when compared to the meat of normal pigs, was characterized by higher pH, lower EC (Electrical Conductivity) and drip loss; it was also tenderer and obtained higher scores in sensory evaluation of taste, smell, and general desirability. Therefore, such raw material can be appreciated by the consumers and can be used for the production of culinary portions similarly to the raw material obtained from normal pigs.
Encapsulation is a process in which a base material is encapsulated in a wall material that can protect it against external factors and/or improve its bioavailability. Among the different ...encapsulation techniques, ionic gelation stands out as being useful for thermolabile compounds. The aim of this work was to encapsulate Saccharomyces boulardii by ionic gelation using agavins (A) and whey protein (WP) as wall materials and to evaluate the morphostructural changes that occur during in vitro gastrointestinal digestion. Encapsulations at different levels of A and WP were analyzed using microscopic, spectroscopic and thermal techniques. Encapsulation efficiency and cell viability were evaluated. S. boulardii encapsulated at 5% A: 3.75% WP (AWB6) showed 88.5% cell survival after the simulated gastrointestinal digestion; the bead showed a significantly different microstructure from the controls. The mixture of A and WP increased in the survival of S. boulardii respect to those encapsulated with alginate, A or WP alone. The binary material mixture simultaneously allowed a controlled release of S. boulardii by mostly diffusive Fickian mechanisms and swelling. The cell-release time was found to control the increment of the Damköhler number when A and WP were substrates for S. boulardii, in this way allowing greater protection against gastrointestinal conditions.
Equine endometrosis is a multifactorial chronic degenerative condition, considered to be one of a major causes of equine infertility. The formation of periglandular fibrosis seems to be linked to ...chronic inflammation of the mare endometrium in a paracrine way and in a response to numerous forms of inflammatory stimuli elicit the net deposition of extracellular matrix (ECM) around the endometrial glands and stroma. We hypothesized some of these stimuli, such as monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and hyaluronan synthases (HASs), may share the nuclear factor-κB (NF-κB) dependent activation pathway. This study aimed to determine whether mRNA expression of MCP-1, IL-6, HASs, and proteins of canonical (RelA/NK-κβ1) and noncanonical (NK-κβ2) signaling pathways for NF-kB would change in subsequent categories of endometrosis during the estrous cycle. The expression of selected genes was established in mare endometrium (n = 80; Kenney and Doig categories I, IIA, IIB, III), obtained in the follicular phase (FLP) and mid-luteal phase (MLP). The high expression of RelA mRNA was observed in III, whereas of NK-κβ1 and NK-κβ2 also in IIA, and IIA and IIB, respectively. The expression of MCP-1 mRNA occurred constantly, regardless of the category, whereas IL-6 mRNA was low in IIA, IIB, and III. The expression of HAS 1 was high in IIA and HAS 3 in IIA, IIB, and III. All those changes were observed in FLP, but not MLP. Our results suggest that NF-κB may be involved in progression of the chronic degenerative condition of the mare endometrium, on both canonical and noncanonical pathways. The most important changes in target genes expression were observed only in FLP, which may suggest the hormone-dependent activation of the NF-κB-dependent fibrosis pathway.
•Pathogenesis of endometrosis.•Canonical, noncanonical activation.•HAS1 HAS2 HAS3.
PDF
