ISO Group Research Articles

Effects of isotretinoin on tooth movement, orthodontically induced and non-orthodontic root resorption: A micro-CT study.

This study aims to investigate whether cumulative dose-dependent isotretinoin (Roaccutane®) could affect orthodontic tooth movement (OTM) and root resorption. Ninety male Wistar Albino rats were divided into 4 groups. While, the control (SALINE), solvent (SOYBEAN) and orthodontic drug (ISOTM) groups underwent orthodontic force, the non-orthodontic drug group (ISO) did not. The rats were administrated saline, soybean oil (SBO) and isotretinoin diluted in SBO (ISOTM, ISO) for 30 days, respectively. Six rats were euthanized in each orthodontic group. Fifty grams of orthodontic force was applied to the remaining rats' first molars using the incisors as anchorage. Six more rats in each group were euthanized on the 7th, 14th and 21st days of the force application. In the ISO group, six rats were euthanized on the 37th, 44th and 51st days of administration. Six rats that were euthanized for ISOTM on the 30th day were also used for ISO to reduce the number of rats used. Micro-computed tomography (micro-CT) and histological analysis were performed. Independent of orthodontic force, isotretinoin caused root resorption in the apical region. However, there was no statistically significant influence of isotretinoin on OTM and orthodontically induced root resorption (OIRR). Despite the lack of strong evidence supporting the orthodontically induced resorptive effect of isotretinoin, this study provided findings regarding the resorptive effects of isotretinoin on non-orthodontic root resorption. Therefore, the present results underscore the importance of close monitoring during orthodontic treatment to mitigate potential root resorption in patients who use isotretinoin because of acne complaints.

Isoflurane-induced neuroinflammation and NKCC1/KCC2 dysregulation result in long-term cognitive disorder in neonatal mice

BackgroundThe inhalational anesthetic isoflurane is commonly utilized in clinical practice, particularly in the field of pediatric anesthesia. Research has demonstrated its capacity to induce neuroinflammation and long-term behavioral disorders; however, the underlying mechanism remains unclear [1]. The cation-chloride cotransporters Na+–K+–2Cl−–1 (NKCC1) and K+–2Cl−–2 (KCC2) play a pivotal role in regulating neuronal responses to gamma-aminobutyric acid (GABA) [2]. Imbalances in NKCC1/KCC2 can disrupt GABA neurotransmission, potentially leading to neural circuit hyperexcitability and reduced inhibition following neonatal exposure to anesthesia [3]. Therefore, this study postulates that anesthetics have the potential to dysregulate NKCC1 and/or KCC2 during brain development.MethodsWe administered 1.5% isoflurane anesthesia to neonatal rats for a duration of 4 h at postnatal day 7 (PND7). Anxiety levels were assessed using the open field test at PND28, while cognitive function was evaluated using the Morris water maze test between PND31 and PND34. Protein levels of NKCC1, KCC2, BDNF, and phosphorylated ERK (P-ERK) in the hippocampus were measured through Western blotting analysis. Pro-inflammatory cytokines IL-1β, IL-6, and TNF-α were quantified using ELISA.ResultsWe observed a decrease in locomotion trajectories within the central region and a significantly shorter total distance in the ISO group compared to CON pups, indicating that isoflurane induces anxiety-like behavior. In the Morris water maze (MWM) test, rats exposed to isoflurane exhibited prolonged escape latency onto the platform. Additionally, isoflurane administration resulted in reduced time spent crossing in the MWM experiment at PND34, suggesting long-term impairment of memory function. Furthermore, we found that isoflurane triggered activation of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α; downregulated KCC2/BDNF/P-ERK expression; and increased the NKCC1/KCC2 ratio in the hippocampus of PND7 rats. Bumetadine (NKCC1 specific inhibitors) reversed cognitive damage and effective disorder induced by isoflurane in neonatal rats by inhibiting TNF-α activation, normalizing IL-6 and IL-1β levels, restoring KCC2 expression levels as well as BDNF and ERK signaling pathways. Based on these findings, it can be speculated that BDNF, P-ERK, IL-1β, IL-6 and TNF - α may act downstream of the NKCC1/KCC2 pathway.ConclusionsOur findings provide evidence that isoflurane administration in neonatal rats leads to persistent cognitive deficits through dysregulation of the Cation-Chloride Cotransporters NKCC1 and KCC2, BDNF, p-ERK proteins, as well as neuroinflammatory processes.

Nonassociative cosmological solitonic R-flux deformations in gauge gravity and G. Perelman geometric flow thermodynamics

We elaborate on a model of nonassociative and noncommutative gauge gravity for the de Sitter gauge group SO(4,1) embedding extensions of the affine structure group Af(4,1) and the Poincaré group ISO(3,1). Such nonassociative gauge gravity theories are determined by star product R-flux deformations in string theory and can be considered as new avenues to quantum gravity and geometric and quantum information theories. We analyse physically important and geometric thermodynamic properties of new classes of generic off-diagonal cosmological solitonic solutions encoding nonassociative effective sources. Particularly, we focus on modelling by such solutions of locally anisotropic and inhomogeneous dark matter and dark energy structures generated as nonassociative solitonic hierarchies. Such accelerating cosmological evolution scenarios cannot be described in the framework of the Bekenstein–Hawking thermodynamic formalism. This motivates a change in the gravitational thermodynamic paradigm by considering nonassociative and relativistic generalizations of the concept of W-entropy in the theory of Ricci flows. Finally, we compute the corresponding modified G. Perelman’s thermodynamic variables and analyse the temperature-like evolution of cosmological constants determined by nonassociative cosmological flows.

Stationary trajectories in Minkowski spacetimes

We determine the conjugacy classes of the Poincaré group ISO+(n, 1) and apply this to classify the stationary trajectories of Minkowski spacetimes in terms of timelike Killing vectors. Stationary trajectories are the orbits of timelike Killing vectors and, equivalently, the solutions to Frenet–Serret equations with constant curvature coefficients. We extend the 3 + 1 Minkowski spacetime Frenet–Serret equations due to Letaw to Minkowski spacetimes of arbitrary dimension. We present the explicit families of stationary trajectories in 4 + 1 Minkowski spacetime.

P2X7 receptor is essential for ST36-attenuated cardiac fibrosisupon beta-adrenergic insult.

P2X7 receptor (P2X7R) plays an important role in modulating inflammation and fibrosis, but information is limited whether Zusanli (ST36) can inhibit inflammation and fibrosis by regulating P2X7R. Isoprenaline at 5mg/kg was subcutaneously injected to wild-type and P2X7R knockout mice for 7 days, while treatment groups received electroacupuncture (EA) stimulation at ST36 for 7 sessions. Following 7-session treatment, Masson's trichrome staining was performed to assess the fibrosis. Morphology, electrocardiogram, and echocardiography were carried out to evaluate the cardiac function and structure. Western blotting, hematoxylin and eosin staining, immunohistochemistry, and biochemical analysis of inflammatory cytokine and transmission electron microscopy were carried out to characterize the effect of ST36 on inflammation. P2X7R was overexpressed in ISO-treated mice. EA at ST36, but not at non-points, reduced ISO-induced cardiac fibrosis, increases in HW/BW, R+S wave relative to mice in ISO groups. In addition, EA at ST36 downregulated ISO-upregulated P2X7R and NLRP3 in ventricle. Moreover, EA reduced cytokines of IL-1β, IL-6, and IL-18 in serum, and inhibited foam cell gathering, inflammatory cell infiltration, and autophagy. However, EA at ST36 failed to attenuate the cardiac fibrosis and hypertrophy in P2X7R knockout mice. In conclusion, EA at ST36 attenuated ISO-induced fibrosis possibly via P2X7R.

Symmetry, Music and Water

There is a deep link existing between symmetry and nature that may be best apprehended by using group theory. In physics, giving a symmetry group is entirely equivalent to fix natural laws (Noether’s theorem). Within such a framework, it follows that all fundamental mechanical laws may be given by defining a group of symmetry operations belonging to the Gal (3,1) symmetry group having ten generators (3 + 3 + 3 + 1 = 10). The move to special relativity amounts simply to substitute another group ISO (3,1) to Gal (3,1) and having the same number of generators. In both cases, one immediately perceives that we live in universe with 3 dimensions of space and 1 dimension of time. A further progress could be made by looking for the symmetry group that leaves Maxwell’s equations invariant. The answer to this fundamental question is the group ISO (4,2) ⊗U (2) ⊗U (2) characterized by 23 generators: 15 = 10 + 5 for the conformal group ISO(4,2), 4 for U(2) and hence 8 = 4 + 4 for the compact part U(2) ⊗U(2) that could be related to the existence of quantum physics besides relativity. As ISO (3,1) is a sub-group of ISO (4,2), the two numbers 4 and 2 suggests that, taking into account the existence of light besides matter, we live in an universe having 4 spacelike dimensions and 2 time-like dimensions. Here, it is proposed that, as music is characterized by a scale-invariant symmetry operation (transposition by octaves) and that as time may be perceived differently in shamanic trance for instance, the two “new” dimensions of our universe may be related to music and consciousness. Related to the fifth dimension of music, the notion of diapason linking physical frequencies to a musical note is revisited. It is thus proposed to adopt a new A4 = 429.62 Hz value based on universal physical constants of our universe and on the mass of the water molecule H₂O, "The most abundant heteronuclear molecule in the entire universe". Demonstration is done that this new diapason is superior to other diapasons based on frequencies of 440 Hz or even 432 Hz.

Exploring the molecular mechanism of Epimedium brevicornu Maxim. in treating breast cancer via network pharmacology and in vitro experiments

ObjectiveTo evaluate the therapeutic effects of Epimedium brevicornu Maxim. (EBM, Yin Yang Huo) on breast cancer using network pharmacology and in vitro validation. It also aimed to explore the novel targets and mechanisms of EBM in the treatment of breast cancer to facilitate the discovery of new drugs and their clinical application. MethodsNetwork pharmacology was used to identify and screen the components and targets of EBM for breast cancer treatment. Molecular docking was further screened the effective components and targets of EBM. Wound-healing assays and flow cytometry analysis were used to detect the ability of two compounds to intervene in the migration and apoptosis of MDA-MB-231 cells, and their mechanism of action was further explored using western blotting experiments. ResultsEBM contained 19 active components. Among them were β-anhydroicaritin (Anhy) and isoliquiritigenin (Iso), which were selected for in vitro experiments. Treatment resulted in a dose-dependent suppression of MDA-MB-231 cell viability, with an IC50 of 23.73 μmol/L for Iso and 21.28 μmol/L for Anhy. In the wound healing assay, cells in Anhy and Iso groups exhibited considerable inhibition of migration at 48 h. In flow cytometry analysis, treatment with Iso (20 μmol/L) for 96 h resulted in significantly higher levels of both early and late apoptosis in the Iso group than that in the control group (P = .004 and P = .014, respectively). Additionally, both Iso (20 μmol/L) and Anhy (10 and 20 μmol/L) induced cell necrosis at 96 h. Western blotting revealed that Anhy and Iso increased the expression of Bax and TBK1/NAK. ConclusionThese findings suggested that Anhy and Iso, the two components of EBM, inhibit MDA-MB-231 cell proliferation and migration of and induce their apoptosis, providing substantial support for future studies on breast cancer.

Strategy to secure the neuraxial route in anaesthesia: Risk mapping and feedback from the application of the ISO 80369-6 standard NRFit® connectors

In anesthesia, a medication error would occur every 20 to 133anesthesia procedures, and 14% is related to a route administration error. To secure neuraxial route, ISO group published a norm in 2016 to develop specific connectors, the "NRFit® connector". The main objective of this work, is to develop a risk mapping related to neuraxial medication errors therefore prepare the NRFit® implementation in anesthesia units in a French Universitary Hospital. Failure modes, effects and criticality analysis (FMECA) methodology was used for our risk mapping which was divided in 3 anesthesia specialities. For each, the analysis was performed for accidental neuraxial administration of intravenous drugs, and its opposite error. Secondly, NRFit® devices were tested for 1month by 3 experimented anesthetists. The majority of reported errors concerns epidural and intrathecal anesthesia, and more frequently in the field of obstetrics. Opioids and tranexamic acid, administered in neuraxial route, are drugs with the highest criticality. The tests were rather conclusive and made it possible to highlight the additional needs in medical devices. Obstetrics is the riskiest area due to the frequency of epidural anesthesia, the administration of critical drugs in intravenous and neuraxial route. This work increased the awareness of our group, improved the measure of this risk and harmonized practices. This work is the first step of the project to prevent administration route error in anesthesia during patient's drug management. The next step will be the NRFit® implementation for epidural and combined spinal-epidural anesthesia in our hospital.

Neuroprotective effect of erythropoietin on anesthesia-induced neurotoxicity through the modulation of autophagy in Caenorhabditis elegans.

The anti-oxidative, anti-inflammatory, and anti-apoptotic effects of erythropoietin may provide neuroprotective effects. Erythropoietin also modulates autophagy signaling that may play a role in anesthesia-induced neurotoxicity (AIN). Herein, we investigated whether AIN can be attenuated by the neuroprotective effect of erythropoietin in the Caenorhabditis elegans (C. elegans). Synchronized worms were divided into the control, Iso, EPO, and EPO-Iso groups. The chemotaxis index (CI) was evaluated when they reached the young adult stage. The lgg-1::GFP-positive puncta per seam cell were used to determine the autophagic events. The erythropoietin-mediated pathway of autophagy was determined by measuring the genetic expression level of let-363, bec-1, atg-7, atg-5, and lgg-3. Increased lgg-1::GFP puncta were observed in the Iso, EPO, and EPO-Iso groups. In the Iso group, only the let-363 level decreased significantly as compared to that in the control group (P = 0.009). bec-1 (P < 0.001), atg-5 (P = 0.012), and lgg-3 (P < 0.001) were expressed significantly more in the EPO-Iso group than in the Iso groups. Repeated isoflurane exposure during development decreased the CI. Erythropoietin could restore the decreased CI by isoflurane significantly in the EPO-Iso group. Erythropoietin showed neuroprotective effects against AIN and modulated the autophagic pathway in C. elegans. This experimental evidence of erythropoietin-related neuroprotection against AIN may be correlated with the induced autophagic degradation process that was sufficient for handling enhanced autophagy induction in erythropoietin-treated worms.

Implication of MAPK, Lipocalin-2, and Fas in the protective action of liposomal resveratrol against isoproterenol-induced kidney injury

Background and ObjectiveIsoproterenol (ISO) is a non-selective β-adrenergic receptor agonist. It can be used to treat bradycardia and cardiogenic shock. Despite its usefulness, the overstimulation of β-receptors by ISO can cause “cardiorenal syndrome,” a term used to describe heart and kidney damage. Resveratrol (RES), a natural polyphenol, has marked anti-inflammatory and antioxidant activities. The present work was designed to study the protective efficacy of liposomal resveratrol (L-RES) against ISO-induced kidney injury. Materials and MethodsThe kidney injury was induced in rats by administering ISO (50 mg/kg, s.c.) twice a week for 2 weeks. RES and L-RES were administered at a dose (20 mg/kg/ day, p.o.) along with ISO for 2 weeks. Inflammatory and apoptotic biomarkers were analyzed, which were validated using histochemical analysis. ResultsISO caused renal dysfunction, which manifested as elevated urea, creatinine and uric acid, besides cystatin c and MAPK protein overexpression. In addition, ISO induced gene expression of Fas and lipocalin-2 and provoked genomic DNA fragmentation in renal tissues as compared with the control group. Histological examination confirmed morphological alterations of the kidney tissues obtained from the ISO group. Concurrent treatment of either RES or L-RES with ISO significantly ameliorated kidney damage as demonstrated by the improvement of all measured parameters with the best results for L-RES. The histopathological findings were correlated with the above biochemical parameters. ConclusionL-RES could be a promising approach for the prevention of kidney injury induced by ISO, most likely via the downregulation of MAPK, cystatin c, Fas, and lipocalin-2.

Empagliflozin treatment prevented oxidative stress, macrophage infiltration, pro-inflammatory and pro-fibrotic responses in the left ventricle of isoprenaline-induced Takotsubo-like syndrome in rats

Abstract Introduction Takotsubo Syndrome (TTS) is an acute heart failure (HF) syndrome induced by both emotional and physical stressors involving a surge of catecholamines and apical ballooning. Currently, there is no specific treatment for TTS. Sodium-glucose cotransporter2 inhibitors (SGLT2i) showed major cardiovascular protective effects in patients with HF independent of glycemic control. SGLT2i have also been shown to have anti-inflammatory and anti-oxidant effects, and to improve the endothelial function in experimental models of cardiac disease. However, a possible protective role of SGLT2i in TTS is unclear. Thus, this study evaluated the effect of SGLT2i on isoprenaline-induced TTS-like syndrome in rats, and determined the underlying mechanism. Methods 32 female Sprague-Dawley rats (10 weeks old) were divided into 4 groups: control, empagliflozin (30 mg/kg/day provided in the diet for 2 weeks), isoprenaline (Iso, 100 mg/kg, i.p.) to induce a TTS-like syndrome, and Iso plus empagliflozin (IE group). After 6 h of Iso injection, echocardiography was performed to determine left ventricular (LV) ejection fraction (EF) by area and heart rate (HR). At day 3, rats were sacrificed, main mesenteric artery and microvessels were collected for vascular reactivity studies, and LV was divided into base and apex to study mRNA expression levels using RT-qPCR, macrophage infiltration by in situ CD68 immunofluorescence staining, and oxidative stress using dihydroethidium. Results The injection of Iso to rats caused at 6 h an increased LVEF and HR in the Iso and the IE groups as compared to their corresponding controls. The HR response was significantly smaller in the IE group compared to Iso group whereas LVEF was similar. In addition, in mesenteric microvessels but not the main mesenteric artery, Iso group showed significant decreased relaxations to acetylcholine and increased contractile responses to phenylephrine in intact rings both of which were not observed in the IE group. Hearts showed significantly increased mRNA levels of IL-1β, TNF-α, NOX2, VCAM-1, MMP-9, TGF-β1 and collagen-1, oxidative stress levels and CD68 staining in the apex compared to the base in the ISO group, all of which were significantly reduced in IE group. Conclusions The present findings indicate that ISO injection caused in the LV elevated levels of oxidative stress, macrophage infiltration, pro-inflammatory, pro-remodeling and pro-fibrosis responses that were more pronounced in the apex compared to the base, and also endothelial dysfunction in the systemic microcirculation, all of which were significantly prevented by the empagliflozin treatment. They further suggest that SGLT2 appears as an interesting target in TTS.

Targeting PD-1/PD-L1 inhibits rejection in a heterotopic tracheal allograft model of lung transplantation.

Immune checkpoint molecules such as programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have revolutionized the field of lung cancer treatment. As part of our study, we examined the role of these proteins in acute rejection in a mouse model of heterotopic tracheal transplantation. Recipient mice were untreated (Allo group) or treated with anti-PD-L1 (aPDL1 group) or PD-L1 Fc recombinant protein (PD-L1 Fc group). A further group of C57BL/6 mice received isografts (Iso group). The occlusion rate was significantly higher in the Allo group than in the Iso group (p = 0.0075), and also higher in the aPD-L1 group (p = 0.0066) and lower in the PD-L1 Fc group (p = 0.030) than in the Allo group. PD-L1 Fc recombinant protein treatment significantly decreased interleukin-6 and interferon-γ levels and reduced the CD4+/CD8+ T cell ratio, without increasing PD-1 and T-cell immunoglobulin mucin 3 expression in CD4+ T cells. These data suggest that PD-L1 Fc recombinant protein decreases the levels of inflammatory cytokines and the proportion of CD4+ T cells without exhaustion. The PD-L1-mediated immune checkpoint mechanism was associated with rejection in the murine tracheal transplant model, suggesting a potential novel target for immunotherapy in lung transplantation.

Study on the Specific Expression of Infrared Radiation Temperature on the Body Surface of Acupoint in Rats with Chronic Myocardial Ischemic Injury.

Infrared thermal imaging technology was used to observe the changes in infrared radiation temperature at acupoints in rats caused by chronic myocardial ischemia injury. This study aims to compare the difference of body surface infrared radiation temperature information of three groups of acupoints: bilateral Neiguan (PC6), bilateral Yanglingquan (GB33), and bilateral Sham Acupoints (SA) in the pathological state of myocardial ischemia injury, and to explore the relationship between acupoints and viscera state. SPF adult Wistar male rats (n = 20) were randomly divided into a control (CTL; n = 10) and an isoproterenol group (ISO; n = 10). Chronic myocardial injury was induced in rats by subcutaneous injection of isoproterenol hydrochloride for 14 d. On the second day after the establishment of the model, the serum levels of cardiac troponin (cTnI) and creatine kinase isoenzyme (CK-MB) were measured by enzyme-linked immunosorbent assay (ELISA). The morphological changes of the myocardial tissue in the two groups were observed by hematoxylin-eosin (HE) staining and their pathological scores were evaluated, which was then used to determine the myocardial ischemic injury. Two days before and after the establishment of the model, the electrocardiograms (ECG) of the two groups of rats were recorded by the (ECG) data acquisition system, and the infrared thermal imaging platform was used to detect the temperature of the six acupoints. 1. After subcutaneous injection of isoproterenol hydrochloride for 14 days, the ST segment of the ECG decreased in the ISO group compared with that of the CTL group; 2. Myocardial tissue injury was serious in the ISO group compared to the CTL group; 3. Serum cTn-I and CK-MB were significantly increased (P <0 01) in the ISO group, compared to that in the CTL group; 4. The infrared radiation temperature on the body surface of bilateral Neiguan (PC6) acupoints decreased significantly in the ISO group, compared to that of the CTL group. Infrared thermal imaging technology can be used to detect the changes in the energy state of acupoints. Chronic myocardial ischemic injury can cause a decrease in IR temperature on the body surface of bilateral Neiguan (PC6) acupoints, suggesting that visceral diseases can lead to changes in the energy metabolism of acupoints.

The Detrimental Effect of Pre-Treatment with Ivermectin on Myocardial Ischemia

Introduction: Ivermectin (IVM) is a broad-spectrum anti-parasitic agent with potential antibacterial, antiviral, and anti-cancer effects. There are limited studies on the effects of IVM on cardiovascular diseases, so the present study sought to determine the effects of pre-treatment with IVM on myocardial ischemia in both ex vivo and in vivo. Methods: In the ex vivo part, two groups of control and treated rats with IVM (0.2 mg/kg) were examined for cardiac function and arrhythmias by isolated heart perfusion. In the in vivo part, four groups, namely, control, IVM, Iso (MI), and Iso + IVM 0.2 mg/kg were used. Subcutaneous injection of isoproterenol (100 mg/kg/day) for 2 consecutive days was used for the induction of myocardial infarction (MI) in male Wistar rats. Then electrocardiogram, hemodynamic factors, cardiac hypertrophy, and malondialdehyde (MDA) levels were investigated. Results: The ex vivo results showed that administration of IVM induces cardiac arrhythmia and decreases the left ventricular maximal rate of pressure increase (contractility) and maximal rate of pressure decline (relaxation). The isoproterenol-induced MI model used as an in vivo model showed that cardiac hypertrophy were increased with no improvement in the hemodynamic and electrocardiogram pattern in the IVM-treated group in comparison to MI (Iso) group. However, the MDA level was lower in the IVM-treated group. Conclusion: IVM pre-treatment demonstrates detrimental effects in cardiac ischemia through exacerbation of cardiac arrhythmia, myocardial dysfunction, and increased cardiac hypertrophy. Therefore, the use of IVM in ischemic heart patients should be done with great caution.

Serum Pharmacochemistry Combined with Network Pharmacology-Based Mechanism Prediction and Pharmacological Validation of Zhenwu Decoction on Alleviating Isoprenaline-Induced Heart Failure Injury in Rats.

Zhenwu decoction (ZWD) is a famous classical formula in the treatment of heart failure (HF) with significant clinical effects. Owing to the complex material basis of ZWD, it is challenging to elucidate the pharmacodynamic substances and pharmacological mechanisms of ZWD against HF. Therefore, an ultrahigh-performance liquid chromatography system coupled with a high-resolution orbitrap mass spectrometry method was used to profile the chemical components and the absorbed prototype constituents in ISO-induced HF rat serum after oral administration of ZWD, and 33 out of 115 compounds were identified. In the in vivo study, ZWD could improve cardiac function and reduce the content of serum biochemical indexes, which are heart failure markers. With the help of network pharmacology and molecular docking simulation analysis, 112 ZWD targets oriented by HF were obtained, with STAT3, TNF, AKT1, VEGFA, and ALB as the core targets. Furthermore, we found that paeoniflorin and its derivatives may play a bigger role than other serum migrant components. Enriched pathway analysis yielded multiple HF-related signaling pathways, which indicated that ZWD may attenuate HF through the effect of PI3K-Akt, and MAPK pathways by regulating key targets such as STAT3, TNF, and AKT1. Finally, STAT3/MAPK pathways were experimentally validated in the anti-HF effect of ZWD. The phosphorylation levels of p38, JNK, ERK, and STAT3 were significantly increased in the ISO group and reversed by ZWD intervention. The results provided a reasonable strategy for the rapid screening of bioactive components in ZWD and a reference for quality control and further mechanism study of ZWD.

Pregnancy hypertension-associated endothelial dysfunction is attenuated by isoflurane anesthesia: Evidence of protective effect related to increases in nitric oxide

AimsPregnancy hypertension-induced endothelial dysfunction associated with impairment of nitric oxide (NO) bioavailability and hemodynamic derangements is a challenging for urgent procedures requiring maternal anesthesia. The volatile anesthetic isoflurane has demonstrated NO-associated protective effects. However, this isoflurane-induced effect is still unclear in pregnancy hypertension. Therefore, the present study examined the potential protective effects of isoflurane anesthesia on endothelial dysfunction and hemodynamic changes induced by hypertensive pregnancy associated with fetal and placental growth restrictions. Materials and methodsAnimals were distributed into four groups: normotensive pregnant rats (Preg), anesthetized pregnant rats (Preg+Iso), hypertensive pregnant rats (HTN-Preg), and anesthetized hypertensive pregnant rats (HTN-Preg+Iso). Systolic and diastolic pressures, mean arterial pressure (MAP), heart rate, fetal and placental weights, vascular contraction, endothelium-derived NO-dependent vasodilation, and NO levels were assessed. The vascular endothelial growth factor (VEGF) levels and endothelial NO synthase (eNOS) Serine (1177) phosphorylation (p-eNOS) expression were also examined. Key findingsIsoflurane produced more expressive hypotensive effects in the HTN-Preg+Iso versus Preg+Iso group, with respective reductions in MAP by 50 ± 13 versus 25 ± 4 mmHg (P < 0.05). Also, HTN-Preg+Iso compared to the HTN-Preg group showed (respectively) preventions against the weight loss of the fetuses (4.0 ± 0.6 versus 2.8 ± 0.6 g, P < 0.05) and placentas (0.37 ± 0.06 versus 0.30 ± 0.06 mg, P < 0.05), hyper-reactive vasocontraction response (1.8 ± 0.4 versus 2.8 ± 0.6 g, P < 0.05), impaired endothelium-derived NO-dependent vasodilation (84 ± 8 versus 50 ± 17 %, P < 0.05), reduced VEGF levels (147 ± 46 versus 25 ± 13 pg/mL, P < 0.05), and decreased p-eNOS expression (0.24 ± 0.07 versus 0.09 ± 0.05 arbitrary units, P < 0.05). SignificanceIsoflurane anesthesia protects maternal endothelial function in pregnancy hypertension, and possibly endothelium-derived NO is involved.

A prospective randomized study examining the impact of intravenous versus inhalational anesthesia on postoperative cognitive decline and delirium

The present prospective randomized study was designed to investigate whether the development of Post Operative Cognitive Decline (POCD) is related to anesthesia type in older adults. All patients were screened for delirium and mental status, received baseline neuropsychological assessment, and evaluation of activities of daily living (ADLs). Follow-up assessments were performed at 3-6 months and 12-18 months. Patients were randomized to receive either inhalation anesthesia (ISO) with isoflurane or total intravenous anesthesia (TIVA) with propofol for maintenance anesthesia. ISO (n = 99) and TIVA (n = 100) groups were similar in demographics, preoperative cognition, and incidence of post-operative delirium. Groups did not differ in terms of mean change in memory or executive function from baseline to follow-up. Pre-surgical cognitive function is the only variable predictive of the development of POCD. Anesthetic type was not predictive of POCD. However, ADLs were predictive of post-operative delirium development. Overall, this pilot study represents a prospective, randomized study demonstrating that when examining ISO versus TIVA for maintenance of general anesthesia, there is no significant difference in cognition between anesthetic types. There is also no difference in the occurrence of postoperative delirium. Postoperative cognitive decline was best predicted by lower baseline cognition and functional status.

Cardioprotective effects of Schisantherin A against isoproterenol-induced acute myocardial infarction through amelioration of oxidative stress and inflammation via modulation of PI3K-AKT/Nrf2/ARE and TLR4/MAPK/NF-κB pathways in rats

Background and aimsThe scientific community is concerned about cardiovascular disease mortality and morbidity, especially myocardial infarction (MI). Schisantherin A (SCA), a dibenzocyclooctadiene lignan monomer found in S. chinensis fruits has cardiovascular advantages such as increasing NO production in isolated rat thoracic aorta and reducing heart damage caused by ischemia-reperfusion (I/R) through decreasing apoptosis. The present study was undertaken to explore the potential effects of SCA on ISO-induced myocardial infarction in rats.MethodsRats were randomly allocated to four groups: control; ISO-treated, and two additional groups of ISO + SCA (5 or 10 mg/kg body weight). All SCA-treated groups were administered with SCA for 20 days and all ISO groups were challenged with ISO on days 19 and 20.ResultsSCA significantly attenuated ISO-induced rise in heart/body weight ratio, myocardial infarct size, and cardiac functional biomarkers (CK-MB, cTnI and BNP). SCA pre- and co-treatment resulted in a significant reduction in oxidative stress (via MDA, NO and GSH and increased activities of SOD, CAT and GPx) and inflammation (via decreased levels of TNF-α, IL-6 and IL-1β) markers when compared to the same levels in cardiac tissue of ISO-treated rats. This study also showed that SCA protects ISO-induced oxidative stress and inflammation by activating the PI3K-AKT/Nrf2/ARE pathway and suppressing TLR4/MAPK/NF-κB pathways. Furthermore, SCA treatment protected histopathological alterations observed in only ISO-treated cardiac transverse sections of rats.ConclusionIn conclusion, the findings of this study suggest that SCA protects against cardiac injury in the ISO-induced MI model of rats.

Music listening according to the iso principle modulates affective state

Music listening can modulate affective states. Individuals can choose music that is congruent or incongruent with their current affective state. Music therapy intervention manuals suggest that individuals who suffer from mental disorders should listen to music according to the iso principle. This involves listening to music that initially matches the current affective state, and then gradually shifting to listening to music that represents a desired state. In the current study, 59 healthy participants underwent a sadness induction by being shown a movie clip designed to induce sadness. They were subsequently divided into two experimental groups: the iso group and the compensatory group. The iso group listened to a sad song first, followed by a happy song. The compensatory group listened to two happy songs. All participants rated their current affective state prior to and after the sadness induction, and after listening to each of the songs. In addition, trait affect and personality were assessed. The results indicated that the movie clip induced sadness in both experimental groups. After listening to the two songs, the iso group reported significantly lower negative affect than the compensatory group. Final affective state was related to trait affect and personality. We conclude that listening to music according to the iso principle is effective in modulating affective state. Individuals who listen to music according to the iso principle should experience changes of affect in line with the music’s affective shift.

The Validity of Heart Rate Variability Obtained from Electrocardiography and Blood Pressure in Rats Subjected to Isoproterenol-Induced Heart Ischemia.

Heart rate variability (HRV) is calculated by electrocardiography (ECG-HRV) or blood pressure (BP-HRV). The purpose of this study was to determine the validity of the above methods in rats with normal and ischemic hearts during the baroreflex maneuver. The study was conducted at Shiraz University of Medical Sciences, Shiraz, Iran, in 2021. Sprague-Dawley rats were divided into a sham group and an isoproterenol-mediated cardiac ischemia (ISO) group. Saline and isoproterenol (150 mg/kg) injected subcutaneously for 2 consecutive days in the sham and ISO groups, respectively. Then, the animals were anesthetized with an intraperitoneal injection of sodium thiopental (60 mg/kg), and the femoral artery and vein were cannulated. Baroreflex was activated using an intravenous injection of phenylephrine (10 μg/100 μL saline). ECG, BP, and heart rate (HR) were recorded, and the time domain of HRV and baroreflex gain were calculated. Baroreflex gain in the ISO group (male, weight=275.8±2.8 g, n=8) was lower than that in the sham group (male, weight=258±2.3 g, n=8) (P<0.05). ECG-HRV indicated an increase in the standard deviation of the RR interval (SDRR), the index of overall HRV, and the parasympathetic index of the root mean square of successive differences (RMSSD) in both groups. However, the rise in SDRR and RMSSD in the ISO group was less than that in the sham group (P<0.05). SDRR and RMSSD obtained from BP did not show a difference between the sham and ISO groups, nor did they correspond with the results seen in baroreflex gain. BP-HRV was not as valuable as ECG-HRV in assessing cardiac ischemia.