Journal of Physiology and Pharmacology最新文献

The aim of the study was to evaluate hypoxia-inducible factor 1alpha (HIF-1α) concentrations in follicular fluid (FF) and serum of patients undergoing controlled ovarian stimulation during in vitro fertilization (IVF) procedure and their potential relationship with the development of ovarian hyperstimulation syndrome (OHSS). An observational case-control study was conducted over 3 years, including 148 patients undergoing IVF treatment: 48 patients in the natural cycle (control group), 49 patients in the GnRH agonist protocol group (group 2) and 51 women in the GnRH antagonist protocol group (group 3). Blood and FF samples were collected on the day of oocyte retrieval and HIF-1α concentrations were assessed using enzyme-linked immunosorbent assay (ELISA). OHSS was diagnosed according to the Golan classification. Binomial logistic regression was used to show the change in the probability of OHSS associated with the concentration of HIF-1α. Finally, the ROC curve was created to check the usefulness of HIF-1α in the identification of OHSS. In all groups HIF-1α concentrations were lower in serum than in FF. There was no difference between the groups in the HIF-1α FF concentrations. Serum HIF-1α level was significantly lower in group 2 and 3 in comparison to the control group (320.35±148.83 pg/ml vs. 287.86±111.03 pg/ml and respectively vs. 490.38±249.36; p=0.0003 and p<0.000001). The overall incidence of OHSS in the entire study was 18.9%. There was no case of OHSS in the control group and no difference between group 2 and 3 in the incidence of OHSS. The OR of serum HIF-1α levels for probability of developing OHSS was estimated on 0.997 (95% CI 0.995-0.99962, p=0.024). The ROC curve analysis showed the optimal cutpoint for HIF-1α of 1015 pg/ml (with the 54% sensitivity and 65% specificity). During controlled ovarian stimulation lower serum level of HIF-1α on the day of oocyte retrieval is related to the higher risk of developing OHSS.

Changes in breathing pattern and breathing pattern variability have been associated with a wide spectrum of pathological states. Obesity is associated with changed mechanical properties of the chest potentially influencing breathing pattern. However, there is only limited information on changes in the breathing pattern in young individuals with obesity and the variability of the breathing pattern has not yet been investigated. Therefore, the aim of this study was to assess the breathing pattern changes in young individuals with obesity, focusing on its variability. We investigated 47 patients with obesity and 47 sex and age matched control subjects, mean age 17.6 years. Tidal volume and duration of inspiration and expiration were breath-to-breath recorded using respiratory inductive plethysmography method during five consecutive phases. Further we calculated following parameters: respiratory cycle duration (Ttot), respiratory rate (fR), minute ventilation (MV), the duty cycle (Ti/Ttot), mean inspiratory flow (Vt/Ti) and a measure of rapid shallow breathing (fR/Vt). Mean values of all respiratory parameters were used as representative values for the given phase and their variability was quantified using standard deviation (SD) and coefficient of variation (CV). Patients with obesity were characterized by reduced Vt and increased fR mostly at rest and by a decreased expiration duration resulting in an increase in Ti/Ttot ratio. While Vt/Ti did not differ between two groups, fR/Vt ratio was significantly increased in the obese group. Concerning respiratory variability, we found an increased variability of several respiratory parameters (respiratory rate, minute ventilation, inspiratory flow, Ti/Ttot ratio, fR/Vt ratio) in patients with obesity mostly at rest. We conclude that initial changes in breathing pattern and breathing pattern variability are already present in young patients with obesity. These changes could serve as a potential marker to distinguish patients with increased risk of developing obesity related respiratory complications.

Etomidate plays a protective role in ischemia/reperfusion diseases. The aim of this study was to investigate its mechanism in ameliorating myocardial ischemia/reperfusion injury (MI/RI). Experimental models of MI/RI in rats and hypoxia/reoxygenation (H/R) injury in H9c2 cardiomyocytes were established to examine the myocardial protective properties of Etomidate. The effects of Etomidate on myocardial tissue damage were evaluated by echocardiography, serum cardiac enzymes, myocardial hematoxylin and eosin (H&E) staining and Masson staining. Cardiomyocyte injury was determined by detecting cell viability and the levels of lactate dehydrogenase. Mitochondrial function of cardiomyocytes was assessed by mitochondrial membrane potential, adenosine triphosphate (ATP) content, and mitochondrial reactive oxygen species (ROS). Iron content, oxidative- and ferroptosis-related biomarkers were measured. Ferroptosis inducer Erastin was utilized for mechanistic investigation. In results Etomidate alleviated ischemia/reperfusion-induced myocardial injury, ferroptosis and mitochondrial injury in rats in a dose-dependent pattern. Etomidate also increased cell viability, attenuated mitochondrial damage, and reduced intracellular iron and lipid peroxidation in cardiomyocytes with hypoxia-reoxygenation (H/R) injury. Moreover, the protective effects of Etomidate against MI/RI or H/R injury were abolished by Erastin intervention. Our study elucidated the correlation between Etomidate and ferroptosis and mitochondrial damage following MI/RI, concluding that Etomidate may exert a protective effect against MI/RI by mitigating ferroptosis and mitochondrial damage. This discovery provides novel insights into the pharmacological mechanisms of Etomidate in the context of MI/RI.

Percutaneous endoscopic gastrostomy (PEG) and percutaneous endoscopic jejunostomy (PEJ) tube placement are standard procedures for artificially administered nutrition support in malnourished patients. However, minor and major complications can occur. Peristomal infections are most common, potentially leading to severe inflammation, hospitalization, and PEG/PEJ removal. Antibiotic prophylaxis is effective in preventing peristomal infections and recommended by current guidelines but does not seem to be systematically used. The present study evaluated the implementation of prophylactic antibiosis in PEG/PEJ placement in clinical routine in Germany. A web-based survey was conducted among hospitals, ambulatory health care centers, and focus practice. In total, 107 participants have finalized the questionnaire. Most participants were from major regional and maximum care facilities (36.4%), basic and standard care facilities (28.0%), as well as university facilities (23.4%). Routine antibiotic prophylaxis for every PEG/PEJ procedure is performed by 42.6%, whereas 13.9% do not apply antibiotic prophylaxis in general, and 23.8% only use it in patients with risk factors for infectious complications. This decision is based on in-house guidelines in 34.0% of participants or national recommendations 20.2%, whereas international guidelines (8.5%) and other recommendations play a minor role (4.3%). Although prophylactic antibiosis in PEG/PEJ placement is effective and recommended by current guidelines, less than half of the sites reported to routinely apply it. Given that these recommendations are based on outdated evidence, updated data is needed, and guideline recommendations need to be re-evaluated accordingly and fully implemented.

To investigate the effect and mechanism of etomidate on attenuating Alzheimer-like neuropathology and cognitive impairment in mice with Alzheimer's disease (AD). AD was modeled in vivo using amyloid precursor protein/presenilin 1 (APP/PS1) mice. After etomidate treatment, behavioral experiments and histopathological observation of hippocampus were performed. Hippocampal Aβ deposition was detected using immunofluorescence. AD was modeled in vitro using a HT22 cells which are an immortalized cell line derived from primary mouse hippocampal neurons induced by Aβ1-42. Cell viability, apoptosis rate and LDH release were detected after etomidate intervention. Synaptic proteins were detected by mmunofluorescence or Western blot, and neurotransmitters and inflammatory factors were detected by ELISA. Etomidate improved the memory ability, novel object cognition ability, and spatial learning of APP/PS1 mice. The improvement of cognitive function and memory ability may be due to the recovery effect of etomidate on hippocampal pathological changes in APP/PS1 mice, including reducing Aβ deposition, neuron and synaptic loss. Etomidate also regulated neuroinflammation and the release of neurotransmitters GABA and 5-HT in APP/PS1 mice. Etomidate effectively reversed Aβ1-42-induced hippocampal neuronal damage, which was reflected in the improvement of cell viability and the inhibition of cytotoxicity, apoptosis and pro-inflammatory factors. Etomidate reversed the inhibition of the expression of synaptophysin (SYP) and postsynaptic density protein-95 (PSD-95) induced by Aβ1-42 in vitro. After etomidate intervention, the expression of serotonin 1A receptor (5HT1A) and gamma-aminobutyric acid type A receptor subunit alpha1 (GABRA1) in Aβ1-42-injured HT22 cells were up-regulated, and free calcium ion was increased. In conclusion, etomidate ameliorates Alzheimer-like neuropathology and cognitive impairment in APP/PS1 mice, indicating that etomidate may be a potentially useful drug for the treatment of AD.

Inflammation in the reproductive organs is a serious threat to human and animal fertility. Recently, the possible role of peroxisome proliferator-activated receptor (PPAR) ligands as potential regulators of endometrial inflammation has been proposed. The aim of the present study was to investigate the effect of PPARβ/δ ligands on mRNA abundance and protein secretion of selected inflammatory mediators - interleukin (IL)-1β, IL-6, IL-8, IL-4, IL-10, tumor necrosis factor alpha (TNF-α), leukemia inhibitory factor (LIF), toll-like receptor 4 (TLR4) and nuclear factor kappaB (NF-κB) - in porcine endometrium during physiology and lipopolysaccharide (LPS)-stimulated inflammation in both the mid-luteal and follicular phases of the estrous cycle. In addition, two experimental setups - an ongoing and a developing inflammation - were considered. Sections of endometrial tissue were incubated in vitro with two selected PPARβ/δ ligands: agonist L-165,041 or antagonist GSK 3787 with or without LPS. The mRNA abundance was determined by real time polymerase chain reaction (RT-PCR) and protein secretion in the culture medium by enzyme-linked immunosorbent assay (ELISA). Both PPARβ/δ ligands increased the mRNA abundance of IL-1β, IL-6 and IL-8 in the inflammatory state and decreased IL-4 protein secretion in the physiological state, mainly in the mid-luteal phase of the estrous cycle. In turn, only the antagonist increased TNF-α expression. For all proinflammatory cytokines - IL-1β, IL-6, IL-8, TNF-α - we found that both hormonal and inflammatory status significantly influenced their mRNA levels, while the experimental setup notably affected the expression of IL-1β, IL-6 and TNF-α. The results show that PPARβ/δ ligands modulate the expression and secretion of cytokines involved in the inflammatory response in the porcine endometrium. The main effect of PPARβ/δ ligands was noted during the mid-luteal phase of the estrous cycle. During LPS-stimulated inflammation, PPARβ/δ ligands appear to have pro-inflammatory properties by stimulating the expression of IL-1β, IL-6, IL-8, TNF-α. The changes in the expression of immune mediators depend on the phase of the estrous cycle or the course of endometritis.

The objective of this study was to investigate the mechanism by which insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) interacts with downstream target genes to influence the progression of triple-negative breast cancer (TNBC). The study involved a total of 80 tissue samples collected from various types of breast cancer tumors and benign breast tumors. The gene expression levels of IGF2BP2 in the samples were quantified using real-time quantitative reverse transcription PCR (qRT-PCR). The abilities of cell proliferation, apoptosis, migration, and invasion in human breast cancer cells (MBA-MD-231), as well as the expression of CCL20 and c-MYC following IGF2BP2 transfection, were measured. The binding of IGF2BP2 to CCL20 and c-MYC mRNA and the methylation levels of CCL20 and c-MYC after IGF2BP2 overexpression were detected using RNA immunoprecipitation-qRT-PCR (RIP-qRT-PCR). As a result, we found: 1) the expression of IGF2BP2 was elevated in all subtypes of breast cancer compared to the benign breast tumor group, with significant differences in the HER-2 overexpression and TNBC groups; 2) IGF2BP2 could promote cell proliferation, invasion, and migration capabilities. Notably, there was no significant difference in apoptosis rate in the experimental group with IGF2BP2 overexpression, while the apoptosis rate significantly increased in the experimental group where IGF2BP2 was silenced. The IGF2BP2 upregulated the expression of CCL20 and c-MYC, directly binding with both, with a significant increase in the methylation levels of CCL20 and c-MYC following IGF2BP2 overexpression. Our results indicate that IGF2BP2 exhibited differential expression across different molecular subtypes of breast cancer, with notable upregulation in triple-negative and HER-2 overexpression breast cancers. IGF2BP2 was found to promote the proliferation, invasion, and migration of TNBC, with no significant effect on apoptosis. By directly binding to CCL20 and c-MYC, it played a role in regulating the progression of TNBC by enhancing the methylation levels of both of these target genes.

Sea buckthorn (Hippophae rhamnoides L.) has many beneficial health properties. In our previous study we showed suppression of hyperglycaemia, water intake, decreased sorbitol levels in the lens of the eyes after sea buckthorn m(Hippophae rhamnoides L.) treatment in Zucker diabetic fatty rats (animal model of type 2 diabetes mellitus, T2DM) with better antioxidant properties of dried berries. Afterwards, we decided to compare the effects of metformin (150 mg/kg b.wt.) and sea buckthorn dried berries (500 or 1000 mg/kg b.wt.) or leaves infusion per os administration on the liver histology in Zucker diabetic fatty (ZDF) rats. Moreover, following biochemical parameters in the blood serum were determined: alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, cholesterol and triglycerides. The histological analyses revealed the appearance of lipid droplets within the liver tissue of diabetic ZDF rats which were not observed in the non-diabetic control animals. Administration of both metformin and sea buckthorn caused a decrease in the number of lipid droplets in the liver. In ZDF rats, an increase in AST, ALP, bilirubin, cholesterol and triglyceride in blood serum was noticed. In comparison with diabetic animals, metformin and sea buckthorn administration did not change the biochemical parameters but only a tendency to reduce some biochemical parameters was noticed. The obtained results suggest that sea buckthorn dried fruits as well as leaves infusion may have biological potential to be used in prevention and treatment of metabolic diseases. Next studies are needed to analyse the exact mechanism of action, develop and promote sea buckthorn berries as a functional food or natural therapeutical products.

This study investigated the effect of edaravone dexborneol (ED) combined with interventional thrombectomy in the treatment of ischemic stroke (IS) in the elderly and its effects on nerve function, cerebral hemodynamic status, and levels of serum amyloid A (SAA), lipoprotein-associated phospholipase A2 (LP-PLA2), and soluble CD40 ligand (sCD40L). One hundred elderly patients with IS were divided into the control group and observation group by random number table method. The control group received conventional treatment after interventional thrombectomy, and the observation group received conventional treatment and ED treatment after interventional thrombectomy. After 14 days of treatment, the therapeutic effect was evaluated according to the National Institutes of Health Stroke Scale (NIHSS). Neurological function, serum brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neuron-specific enolase (NSE), cerebral haemodynamics, indices of oxidative stress, and serum levels of SAA, LP-PLA2, and sCD40L before and after treatment in both groups were compared. The total effective rate of clinical efficacy was higher and the NIHSS score was lower in the observation group than in the control group (P<0.05). The observation group exhibited higher mean blood velocity and mean blood flow, alongside lower characteristic impedance and dynamic resistance, compared to the control group (P<0.05). SAA, LP-PLA2, and sCD40L in the observation group were lower than those in the control group (P<0.05). BDNF, NGF, and SOD in the observation group were higher than those in the control group, and NSE, MDA, and NEF were lower (P<0.05). ED combined with interventional thrombectomy in the treatment of IS in the elderly can improve nerve function, alleviate oxidative stress reaction, reduce levels of SAA, LP-PLA2, and sCD40L, and alleviate inflammatory response.

The B vitamins have been observed to positively influence the prevention of hypertension, with higher intakes of vitamins B6 and B12 shown to reduce blood pressure in hypertensive patients. This study investigated the relationship between blood pressure variability (BPV) and B vitamin levels in patients with essential hypertension (EH). A total of 100 patients with EH and 100 healthy control subjects were selected. BPV indices were measured using ambulatory blood pressure monitoring, which included daytime systolic blood pressure (dSBP), daytime diastolic blood pressure (dDBP), night SBP (nSBP), night DBP (nDBP), 24-hour SBP (24hSBP), 24-hour DBP (24hDBP), 24-hour SBP standard deviation (24hSSD), 24hDBP standard deviation (24hDSD), daytime SBP standard deviation (dSSD), daytime DBP standard deviation (dDSD). Blood samples were collected to measure vitamin B6 and B12 levels. Compared to the healthy group, vitamin B6 and B12 levels in the EH group were significantly lower (P<0.05). Additionally, dSBP, dDBP, nSBP, nDBP, 24hSBP, 24hDBP, 24hSSD, 24hDSD, dSSD, dDSD, nSSD, and nDSD were significantly higher in the EH group than in the healthy group (P<0.05). BPV indices were also significantly lower in the group with higher vitamin B6 and B12 levels compared to the group with lower levels (P<0.05). Furthermore, vitamin B6 and B12 levels in the EH group were negatively correlated with BPV indices (P<0.05). To sum up BPV in patients with EH is associated with B vitamin levels, which may play a role in the progression and control of hypertension-related diseases.