Relaxation Response Research Articles

Physically-based interpretation of abnormal stress relaxation response in glassy polymers

Understanding the mechanical responses of glassy polymers remains a grand scientific challenge for many decades, which plays a central role in the application of these materials. In this work, we have performed stress relaxation tests on a series of glassy polymers. An abnormal rate-dependent stress relaxation response is revealed, featuring as a larger stress drop and smaller quasi-steady-state stress with increasing the initial loading rate. To explore the underlying deformation mechanism, we further carry out a coarse-grained molecular dynamics simulation on glassy polymers, which qualitatively demonstrates the experimental observations. The underlying physical mechanism is revealed to be that a larger initial loading rate can lead to a more-activated structure state of polymers. Based on these findings, we develop a physically-based model by introducing the effective temperature model into the shear transformation zone (STZ) theory. The effective temperature, as an internal variable, can describe the deformation-induced structural evolution of amorphous polymers. The Adam–Gibbs model is then adopted to relate the effective temperature with the transformation rates of STZ sites. Comparison with experimental results shows that the micro-mechanical model can capture the rate-dependent stress–strain relationship in the loading process as well as the abnormal stress relaxation responses. In comparison, it is challenging to rationalize this abnormal behavior based on classic viscoplastic models due to a lack of physical mechanisms. Thus, this work promotes our understanding of the origin of complex mechanical responses of glassy polymers that are strongly related to the evolution of microstructure upon deformation.

Etanercept Prevents Endothelial Dysfunction in Cafeteria Diet-Fed Rats.

: BackgroundObesity is associated with endothelial dysfunction and this relationship is probably mediated in part by inflammation. Objective: The current study evaluated the effects of etanercept, a tumor necrosis factor-alpha (TNF-α) inhibitor, on endothelial and vascular reactivity, endothelial nitric oxide synthase (eNOS) immunoreactivity, and serum and aortic concentrations of TNF-α in a diet-induced rat model. Design and results: Male weanling Wistar rats were exposed to a standard diet and cafeteria diet (CD) for 12 weeks and etanercept was administered during CD treatment. Isolated aortas of the rats were used for isometric tension recording. Carbachol-induced relaxant responses were impaired in CD-fed rats, while etanercept treatment improved these endothelium-dependent relaxations. No significant change was observed in papaverine- and sodium nitroprusside (SNP)-induced relaxant responses. eNOS expression decreased in CD-fed rats, but no change was observed between etanercept-treated CD-fed rats and control rats. CD significantly increased both the serum and the aortic levels of TNF-α, while etanercept treatment suppressed these elevated levels. CD resulted in a significant increase in the body weight of the rats. Etanercept-treated (ETA) CD-fed rats gained less weight than both CD-fed and control rats.

Music moves – Ettlingen dementia study: Protocol of a pragmatic randomised controlled trial

ABSTRACT Introduction Systematic reviews have shown the effectiveness of music in reducing the behavioural and psychological symptoms of dementia (BPSD). Effects of active (i.e. singing) compared to receptive (including vibroacoustic therapy) individual music therapy methods for specific BPSD/dementia sub-types are unclear, for example, that receptive methods (i.e. vibroacoustic therapy) increase parasympathetic responses and active music therapy improves cognitive and emotional functioning. Method A three-armed pragmatic randomised controlled trial will be conducted with German care home residents with dementia. Residents (N = 75) randomly assigned to the two intervention groups (individual active music therapy or individual vibroacoustic therapy) will receive two sessions/week for six weeks plus standard care. The control group will receive only standard care during data collection. The Neuropsychiatric Inventory-Nursing Home will assess BPSD; secondary outcomes include depression, quality of life, activities of daily living, health economy and musical engagement. Outcomes are measured at baseline, post-intervention (6 weeks), and 12-weeks post randomisation. MMSE is used as a screening measure. We hypothesise that individual active music therapy and individual vibroacoustic therapy will reduce BPSD significantly more than standard care. Secondary hypo-theses are increased quality of life and musical engagement and decreased depressivity and health resource usage. Discussion A greater relaxation response is expected in the receptive arm due to the massage-like vibration. Increased cognitive clarity and reduced depression are expected in the active arm. The trial is registered with the German Clinical Trials Register (DRKS00023233).

Randomized Waitlist-Control Trial of a Web-Based Stress-Management and Resiliency Program for Adolescent and Young Adult Cancer Survivors: Protocol for the Bounce Back Study.

BackgroundThe emotional health of adolescent and young adult (AYA) cancer survivors is compromised both during and after cancer treatment. Targeted programs designed to support AYAs’ ability to cope with stress in the years following treatment completion are lacking. Mind-body programs may ameliorate the negative psychological and emotional effects of stress and assist AYAs with managing the psychosocial challenges of early survivorship.ObjectiveOur randomized waitlist-control trial aims to assess the feasibility, acceptability, and preliminary efficacy of a virtual group program (Bounce Back) to promote stress management and resiliency among posttreatment AYAs.MethodsBounce Back is a stress management and resiliency program delivered via videoconference by a trained mental health clinician. Sessions were adapted from an evidence-based mind-body program (Stress Management and Resiliency Training - Relaxation Response Resiliency Program [SMART-3RP]) grounded in relaxation response elicitation, mindfulness, cognitive behavioral therapy, and positive psychology. Seventy-two AYAs (diagnosed with cancer between ages 14 years and 29 years and had completed cancer treatment within the last 5 years) were randomly assigned to the Bounce Back program or waitlist-control group and completed assessments at baseline, 3 months postbaseline, and 6 months postbaseline. The primary aim of the study is to determine the feasibility and acceptability of the Bounce Back program. Descriptive statistics, including means, frequencies, and ranges supplemented by qualitative exit interview feedback will be used to characterize the sample and to summarize feasibility and acceptability. The exploratory aims are to evaluate the preliminary effects of the program on stress coping and psychosocial outcome measures (ie, anxiety, depression) collected across the 3 time points.ResultsThis study was funded by the National Cancer Institute in July 2017. Study procedures were approved by the Dana-Farber Harvard Cancer Center Institutional Review Board in October 2018 (Protocol 18-428). The randomized trial was conducted from July 2019 to March 2021. Quantitative data collection is complete, and qualitative exit interview data collection is ongoing. Results are expected to be published in peer-reviewed journals and presented at local, national, or international meetings in the coming years.ConclusionsFew evidence-based programs exist that tackle the key transitional issues faced by AYA cancer survivors. Future analyses will help us determine the feasibility and acceptability of the Bounce Back program and its impact on AYA stress coping and psychological well-being.Trial RegistrationClinicalTrials.gov NCT03768336; https://clinicaltrials.gov/ct2/show/NCT03768336International Registered Report Identifier (IRRID)DERR1-10.2196/34033

Interfacial behavior of core–shell composite nanoparticles under compression and shear: Influence of polymer shell thickness

HypothesisThe mobility of core–shell nanoparticles partitioned at an air–water interface is strongly governed by the compliance of the polymer shell. ExperimentsThe compressional, relaxation and shear responses of two polymer-coated silica nanoparticles (CPs) were studied using a Langmuir trough and needle interfacial shear rheometer, and the corresponding structures of the particle-laden interfaces were visualized using Brewster angle and scanning electron microscopy. FindingsThe mobility of CPs partitioned at an air–water interface correlates to the polymer MW. In compression, the CPs40-laden interface (silica nanoparticles coated with 40 kDa PVP) showed distinct gas–liquid-solid phase transitions and when the surface pressure was reduced, the compressed particle-laden interface relaxed to its original state. The compressed-state of the CPs8-laden interface did not relax, and wrinkles in the particle-laden film that had formed in compression remained due to greater adhesion between the compressed particles. The increased mobility of the CPs40-laden interface translated to lower surface shear moduli, with the viscoelastic moduli an order of magnitude or more lower in the CPs40-laden interface than the CPs8-laden interface. Ultimately this contributed to changing the stability of particle-stabilized foams, with less mobile interfaces providing improved foam stability.

PENGARUH TERAPI MUSIK KLASIK TERHADAP KECEMASAN PADA PASIEN PRA OPERASI DI RSUD DR. M. YUNUS BENGKULU

Background: Surgery is an invasive procedure by making an incision due to certain indications. Patients who will undergo surgery tend to have high anxiety. Purpose: This study aims to determine the effect of music therapy on preoperative patient anxiety at RSUD Dr. M. Yunus Bengkulu. Method: The study design used a pre-experimental design with one group pretest post test. The population in this study were all preoperative patients in the Flamboyan room of RSUD Dr. M. Yunus Bengkulu. Samples in the study of pre-operative patients who were met during the study were 32 people. the sampling technique uses accidental sampling. Sample criteria include: preoperative patient major surgery. Data collection techniques using primary data in the form of preoperative questionnaires for anxiety measurement. Anxiety questionnaire that HARS (Hamilton Anxiety Rating Scale). The statistical test used is the t-test. Results: The results showed that p = 0,000 <0.05 was significant. There is a significant influence of musik therapy on surgery patient anxiety in Dr. M. Yunus Bengkulu. Conclusion: Musik therapy provides a relaxation response to the body so that it can reduce anxiety levels. It is hoped that nurses can provide modality therapies such as musik therapy to preoperative patients, in order to reduce anxiety that occurs during the operating room. Keywords: Anxiety; Classical musik therapy; Preoperativ

Possible mechanisms in Ficus exasperata ethanol root fraction amelioration of lead-induced corpus cavernosal contractile impairments in male Wistar rats.

Background:Lead exposure is reported to cause impaired male reproductive tract functions often due to elevated oxidative species. F. exasperata leaf extract contains potent phyto-antioxidants with beneficial endothelial functions. Objectives: This study investigates the effect of ethanolic extract of F. exasperata (EEFE) treatment on the corpus cavernosal contractile activity in lead-exposed adult male Wistar rats. Materials & Methods: Corpus cavernosum strips (CS) were excised from control, EEFE only treated (400 mg/kg), lead + EEFE treated and lead only treated (100 mg/kg) male Wistar rats. Cumulative contractile responses of CS to acetylcholine, potassium chloride, and calcium influx were determined. Furthermore, cumulative dose responses to acetylcholine after incubation in LNAME, indomethacin, nifedipine, and acetovanillone were also determined by measuring isometric contractions using Ugo Basile data capsule acquisition system. Results: Relaxation(%) response to cumulative doses of acetylcholine (10-9–10-5 M) was enhanced in EEFE only treated (59%) compared to lead only (45%). Contractile response to KCl (10-60 M) was restrained in control and EEFE cotreated when compared to lead only treated. Preincubation of the CS with nifedipine (10-4 M) suppressed the relaxation(%) in the lead + EEFE co-treated. Preincubation of the CS in indomethacin improved the relaxant response(%) of the CS in EEFE only and lead + EEFE co-treated (53.53% ±2.80 & 54.65%± 2.95 respectively) compared with the lead only treated (45.40%±1.79). Preincubation with L-NAME significantly reduced relaxation response(%) in EEFE only treated group. Relaxation response(%) of the CS was enhanced in the lead + EEFE group after preincubation with acetovanillone. Conclusion: The study suggests that L-type and voltage-gated calcium channels, NO, and potent antioxidant activity, are important in EEFE amelioration of lead-induced contractile impairments.

Irisin relaxes rat thoracic aorta through inhibiting signaling pathways implicating protein kinase C.

Irisin, a newly identified exercise-derived myokine, has been found involved in a peripheral vasodilator effect. However, little is known regarding the potential vascular activity of irisin, and the mechanisms underlying its effects on vascular smooth muscle have not been fully elucidated. This study was aimed to investigate the effects of irisin on vascular smooth muscle contractility in rat thoracic aorta, and the hypothesis that protein kinase C (PKC) may have a role in these effects. Isometric contraction-relaxation responses of thoracic aorta rings were measured with an isolated organ bath model. The steady contraction was induced with 10 µM phenylephrine (PHE), and then the concentration-dependent responses of irisin (0.001-1 µM) were examined. The time-matched vehicle control (double distilled water) group was also formed. To evaluate the role of PKC, endothelium-intact thoracic aorta rings were incubated with 150 nM bisindolylmaleimide I (BIM I) for 20 min before the addition of 10 µM PHE and irisin. Also, a vehicle control group was formed for dimethyl sulfoxide (DMSO). Irisin exerted the vasorelaxant effects at concentrations of 0.01, 0.1, and 1 µM compared to the control group (p < 0.001). Besides, PKC inhibitor BIM I incubation significantly inhibited the relaxation responses induced by varying concentrations of irisin (p: 0.000 for 0.01 µM; p: 0.000 for 0.1 µM; p: 0.000 for 1 µM). However, DMSO, a solvent of BIM I, did not modulate the relaxant effects of irisin (p > 0.05). In conclusion, physiological findings were obtained regarding the functional relaxing effects of irisin in rat thoracic aorta. The findings demonstrated that irisin induces relaxation responses in endothelium-intact thoracic aorta rings in a concentration-dependent manner. Furthermore, this study is the first to report that irisin-induced relaxation responses are regulated probably via activating signaling pathways implicating PKC.

East Meets West in Therapeutic Approaches to the Management of Chronic Pain.

Yoga as a holistic principle, not only practice of asanas or poses, integrates all aspects of the self, with biological, mental, intellectual, and spiritual elements. Yoga encompasses the biopsychosocial medical perspective, which regards pain as a dynamic interaction between physiological, psychological, and social factors. The purpose of this perspective article is to compare and contrast psychological practices such as mindfulness meditation, relaxation response (RR), and cognitive behavioral therapy (CBT) with Yoga in their management of chronic pain. The use of these practices is explored through history, literature, and research studies. Results from scientific studies on Yoga show changes in health-related pain outcomes for patients with chronic pain. The key aspects of Yoga, notably relaxation, positive thinking, and mindfulness, are discussed in relation to mindfulness meditation, RR, and CBT.

Enhancing effect of nicotine on electrical field stimulation elicited contractile responses in isolated rabbit bladder straight muscle; the role of cannabinoid and vanilloid receptors.

Nicotine acts as an agonist of nicotinic acetylcholine receptors (nAChR). These receptors belong to a superfamily of ligand-gated ion channels. We previously demonstrated that nicotine increased electrical field stimulation (EFS)-induced contractile or relaxation responses, possibly by facilitating neurotransmitter release from nerve terminals in various rabbit tissues. Studies have shown that there is an interaction between the endocannabinoid and nicotinic systems. This study aimed to investigate the interaction between nicotine and the endocannabinoid system in the rabbit urine bladder and also investigate the enhancing effect of nicotine on EFS-induced contractile responses in rabbit isolated bladder smooth muscle and its interaction with the endocannabinoid system. The New Zealand albino male adult rabbits were used for this study. Following scarification, the urine bladder was rapidly excised, and then uniform strips were prepared. Each strip was mounted under 1 g isometric resting tension in an organ bath containing 20 mL of Krebs-Henseleit solution. After obtaining EFS-induced contractile responses, 10-4 M concentrations of nicotine were applied to the preparations, and EFS was stopped after 5 stimulations. Following washing, the same experimental procedure was performed with the same tissue in the presence of AM251 (a cannabinoid CB1R antagonist, 10-6 M), AM630 (a cannabinoid CB2R antagonist, 10-6 M), and capsazepine (a vanilloid receptor antagonist, 3 × 10-6 M). Nicotine enhanced the EFS-induced contraction responses by 17.16% ± 2.81% at a 4-Hz stimulation frequency. Cannabinoid receptor antagonists AM251 and AM630 reduced this increasing effect of nicotine although it was not significant and vanilloid receptor antagonist capsazepine did not significantly alter the nicotines' effect. These results show that enhancing effect of nicotine in the smooth muscle of the rabbit bladder, even though it was not significant endocannabinoid system possibly have a role in nicotines' effect.

Cellular and subcellular coherent dynamics, biological functional properties, and system-environment interaction

In this view point paper, we briefly summarize some of the clinical, biochemical and biophysical results obtained in our research on Relaxation Response. We also qualitatively describe the theoretical biophysical model that could link them. Our work points to a unified view of the human biological system activity, joining the dynamics ruling the interactions and correlations of the microscopic components to the knowledge of their specific individual properties in the effort of going beyond a purely atomistic approach.

Gestational Intermittent Hypoxia Programs Hypertensive Response in Female Rat Offspring: Impact of Ovaries.

Obstructive sleep apnea (OSA) is a chronic condition frequently observed in pregnant women. We have shown that gestational intermittent hypoxia (GIH), a hallmark of OSA, leads to sex-specific impairment in the endothelium-dependent relaxation response and an increase in blood pressure in adult male but not female rat offspring. The present study tested the hypothesis that functional ovaries normalize GIH-induced hypertensive response in female offspring. Experiments were done in female offspring of pregnant rats exposed to normoxia or GIH (FIO2 21-10.5% from gestational days 10 to 21). Ovariectomy and sham surgery were performed at 5 weeks of age. Pups born to GIH dams were significantly smaller than the controls, but they exhibited catch-up growth and were similar to controls by 5 weeks of age. Ovariectomy significantly exacerbated bodyweight gain to a similar extent in both control and GIH offspring. Marked increases in blood pressure were observed in pre-pubertal GIH offspring compared to controls; however, after puberty, blood pressure in GIH offspring progressively decreased and became normotensive at adulthood. Ovariectomy led to the maintenance of higher blood pressure in post-pubertal GIH offspring with no significant effect in controls. Vascular contractile and relaxation responses were not affected in the GIH and control offspring; however, ovariectomy selectively decreased endothelium-dependent relaxation response along with a decrease in endothelial nitric oxide synthase expression in the GIH offspring. These findings suggest that functional ovaries are crucial in protecting females against GIH-mediated endothelial dysfunction and hypertension in adulthood.

Editorial: Mind-Body Wellness in Dentistry

Christina DiBona Pastan: It was a September morning, and as I walked into my second-year endodontic resident’s operatory, she presented herself very differently than I had previously observed. She was moving fast, talking fast, and setting up her bracket tray at turbo speed. I was about to mentor her on her first apicoectomy. She began to articulate to me her fear in performing her first surgical procedure, concern that she would perforate the sinus and not be able to control the bleeding—and as all of this was happening, instruments began to fall on the operatory floor. I knew in that moment I could relate, because I once was in her shoes. However, being a long-time practitioner of yoga and meditation, I have evolved into a very different individual and a very different endodontist. More important than the apicoectomy, it was important for me to make her aware that she was not in the right frame of mind and body to perform this procedure on a patient, and it would ultimately compromise the outcome and her patient’s experience. I stepped out of my traditional clinical instructor mode and asked her if I could teach her a breathing skill that I know calms the body and focuses the mind. She agreed, and within minutes, I watched my student’s entire demeanor change. Her body relaxed, her breathing slowed down, and she centered herself. She looked at me with confidence and said, “I think I can do the surgery now.” I knew my resident could perform the surgery, but what she realized is that she was now in the right frame of mind and body to perform surgery. My resident executed the procedure with excellent results, and the patient was happy and at ease. When the clinic session ended, my resident shared her long-time struggles with anxiety and how she found ways to mask it over the years, but in that moment, it had gotten the best of her. In her seventh year of dental education, she was grateful to learn a new skill that helped her personally cope with her anxiety and simultaneously make her a better professional. This led me to pursue a formal training in yoga and meditation and to address the administration at Tufts University School of Dental Medicine on the importance of including mind-body wellness techniques in the curriculum for all students, specifically the ancient practices of yoga, diaphragmatic breathing, and mindfulness meditation. For the past 6 years in my role as Director of Mind-Body Wellness, I have witnessed the positive effects of teaching these practices to our students, incorporating them in the basic science curriculum, preclinical simulation lab, and patient clinic, and the impact it has had on students’ overall personal and professional success. The goal of dental providers is to deliver mindful, compassionate, and empathetic care to patients. This is achieved through competent clinical and technical skills in conjunction with sensitive communication skills. Dentistry is a stressful profession, and when stress is not managed properly in the clinical environment, it can affect this goal. In 1975, Benson et al published an article on the relaxation response, proving that stress not only contributes to health problems but that mental-focus techniques are good for the body and overall wellbeing.¹ The first code of ethics written by the American Dental Association (ADA) in 1866 states, “The dentist should be temperate in all things, keeping mind and body in the best possible health, that his patient may have the benefit of that clearness of judgement and skill which is their right.”² I don’t know if back in 1866 the ADA was thinking of yogic breathing to achieve this goal, but the organization was definitely making the connection between mind-body wellness and its effect on patient care. Whenever the body is relaxed and the mind is clear, we become consciously aware and therefore interact with the world differently. We are more skillful in our actions, we are better communicators and listeners, and we are more patient and kind to others and less reactive—all qualities that are essential for the dental professional. Mind-body wellness has found its place in our institution and enriched our dental curriculum, community relationships, and clinical experiences. The world we live in today challenges us to be temperate in all things, but the choice is ours to strive to keep ourselves healthy in mind and body for ourselves, for our families, and to deliver the best care for our patients. Christina DiBona Pastan, DMD Boston, Massachusetts, USA

Chinese Caterpillar Mushroom, Ophiocordyceps sinensis (Ascomycota), Cold-Water Extract Relaxes the Rat Isolated Bladder

Ophiocordyceps sinensis is a popular medicinal mushroom used for various health conditions, including alleviation of frequent urination, which is a major symptom of overactive bladder (OAB) syndrome. This study aimed to investigate the effect of O. sinensis (OCS02 cultivar) cold-water extract (CWE) against bladder contractility using the organ bath technique. The bladder was removed from male Sprague-Dawley rats and cut into longitudinal strips of 2 mm × 8 mm. In some experiments, the urothelium was removed to study its role in CWE-induced responses. CWE elicited a biphasic response consisting of an immediate, transient contraction that was followed by a sustained relaxation in bladder strips precontracted with carbachol, a muscarinic agonist. Removal of urothelium did not alter the magnitude of the contractile response but significantly attenuated the relaxation response. In the presence of L-NAME (nitric oxide synthase inhibitor) and sodium nitroprusside (nitric oxide donor), CWE-induced transient contraction was enhanced, whereas the relaxation response was significantly reduced. Following preincubation with CWE, the amplitude and the frequency of the spontaneous myogenic contractions induced by carbachol, as well as the contractile response toward calcium, were significantly suppressed. Findings from this study show that the urothelium plays a role in the relaxant effect of CWE. Its mechanisms of action include the regulation of nitric oxide and inhibition of calcium influx.

Stress relaxation and creep response simulation of P92 steam piping under different loading conditions

Stress relaxation and creep response simulation of P92 steam piping under different loading conditions

Targeting IRE1α-JNK-c-Jun/AP-1-sEH Signaling Pathway Improves Myocardial and Coronary Endothelial Function Following Global Myocardial Ischemia/Reperfusion.

Objectives: Endoplasmic reticulum (ER) stress and soluble epoxide hydrolase (sEH) upregulation/activation have been implicated in myocardial ischemia/reperfusion (I/R) injury. We previously reported that ER stress mediates angiotensin II-induced sEH upregulation in coronary endothelium, whether and how ER stress regulates sEH expression to affect postischemic cardiac function remain unexplored. This study aimed to unravel the signaling linkage between ER stress and sEH in an ex vivo model of myocardial I/R injury.Methods: Hearts from male Wistar-Kyoto rats were mounted on a Langendorff apparatus and randomly allocated to 7 groups, including control, I/R (30-min ischemia and 60-min reperfusion), and I/R groups pretreated with one of the following inhibitors: 4-PBA (targeting: ER stress), GSK2850163 (IRE1α), SP600125 (JNK), SR11302 (AP-1), and DCU (sEH). The inhibitor was administered for 15 min before ischemia with a peristaltic pump. Hemodynamic parameters including left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and maximal velocity of contraction (+dp/dtmax) and relaxation (-dp/dtmax) of the left ventricle were continuously recorded using an intraventricular balloon. Endothelial dilator function of the left anterior descending artery was studied in a wire myograph upon completion of reperfusion. The expression of ER stress molecules, JNK, c-Jun, and sEH was determined by western-blot.Results: I/R decreased LVSP (105.5±6.4 vs. 146.9±13.4 mmHg), and increased LVEDP (71.4±3.0 vs. 6.0±2.7 mmHg), with a resultant decreased LVDP (34.1±9.2 vs. 140.9±13.1 mmHg). I/R attenuated +dp/dtmax (651.7±142.1 vs. 2806.6±480.6 mmHg/s) and -dp/dtmax (-580.0±109.6 vs. -2118.0±244.9 mmHg/s) (all ps<0.001). The I/R-induced cardiac dysfunction could be alleviated by 4-PBA (LVSP 119.5±15.6 mmHg, p<0.01; LVEDP 21.2±4.2 mmHg, LVDP 98.3±12.0 mmHg, +dp/dtmax 2166.7±208.4 mmHg/s, and -dp/dtmax -1350.9±99.8 mmHg/s, all ps<0.001), GSK2850163 (LVSP 113.4±10.9 mmHg, p<0.01; LVEDP 37.1±3.1 mmHg, LVDP 76.3±13.9 mmHg, +dp/dtmax 1586.5±263.3 mmHg/s, -dp/dtmax -1127.7±159.9 mmHg/s, all ps<0.001), SP600125 (LVSP 113.9±5.6 mmHg, LVDP 40.5±3.3 mmHg, +dp/dtmax 970.1±89.8 mmHg/s, all ps<0.01), SR11302 (LVSP 97.9±7.5 mmHg, p<0.01; LVEDP 52.7±8.6mmHg, p<0.001; LVDP 45.2±9.8mmHg, p<0.05; +dp/dtmax 1231.5±196.6 mmHg/s, p<0.01; -dp/dtmax -658.3±68.9 mmHg/s, p<0.05), or DCU (LVSP 109.9±4.1 mmHg, p<0.01; LVEDP 11.7±1.8 mmHg, LVDP 98.2±4.9 mmHg, +dp/dtmax 1869.8±121.9 mmHg/s, and -dp/dtmax -1492.3±30.8 mmHg/s, all ps<0.001). The relaxant response of the coronary artery to acetylcholine was decreased after I/R in terms of both magnitude and sensitivity (p<0.001). All inhibitors improved acetylcholine-induced relaxation. Global I/R increased sEH expression and induced ER stress in both myocardium and coronary artery. Inhibition of ER stress or IRE1α downregulated I/R-induced sEH expression and inhibited JNK and c-Jun phosphorylation. Both JNK and AP-1 inhibitors lowered sEH level in myocardium and coronary artery in I/R-injured hearts.Conclusions: This study deciphered the molecular linkage between ER stress and sEH regulation in global I/R insult by uncovering a novel signaling axis of IRE1α-JNK-c-Jun/AP-1-sEH, which provided basis for future research on the therapeutic potential of targeting the IRE1α-JNK-c-Jun/AP-1-sEH axis for ischemic myocardial injury.

Impaired vessel relaxation response and increased infarct size in smooth muscle cannabinoid receptor 1 knockout mice.

Cannabinoids are reported to regulate cardiovascular functions. Cannabinoid receptors 1 (CB1Rs) are widely expressed in both the neuronal system and vascular system, but the contribution of CB1Rs in vascular smooth muscle (CB1RSM) to cardiovascular functions is not clear yet. In this research, we analyzed the effects of CB1RSM on blood pressure, vasoconstriction, and vasodilation abilities by using conditionally CB1R knockout mice (CB1RSMKO). The results show no significant difference in basal blood pressure between the conscious CB1RSMKO and control mice, indicating that CB1RSM is not essential for basal blood pressure maintenance. The constriction of the CB1RSMKO mesenteric artery in vitro was not significantly altered compared with that of the control mice. In contrast, the relaxation to CB1R agonist 2-AG or WIN55212-2 was decreased in CB1RSMKO vessels, suggesting that activation of CB1RSM mediates the vasodilation effect of cannabinoids. Ischemia stroke mouse model was used to further identify the potential function of CB1RSM in pathological conditions, and the results showed that the infarct volume in CB1RSMKO mice is significantly increased compared with the control littermates. These results suggest that vascular CB1R may not play a central role in basal vascular health maintenance but is protective in ischemia states, such as stroke. The protection function may be mediated, at least partly, by the relaxation effect of CB1RSM-dependent activities of endocannabinoids.

Carvedilol ameliorated UK14304-induced vascular relaxation response via AMPK in diabetic mice aortas

Carvedilol ameliorated UK14304-induced vascular relaxation response via AMPK in diabetic mice aortas

Role of telocytes in the pathogenesis of ectopic pregnancy.

The aim of this study is to investigate the effect of telocytes on tubal motility in ectopic pregnancies. This study included patients with ectopic pregnancy (EP) (n=10) and control patients (n=10) (partial salpingectomy for contraception). Immunohistochemical staining for c-Kit, vimentin, CD34 and S100A was performed to quantify telocytes in the mucosa, muscular layer and serosa of fallopian tubes of control and EP group. Spontaneous and KCl- (80 mM) induced contraction and cumulative progesterone dose-relaxation (10-11-10-5 M) and cumulative oxytocin dose-contraction (10-10-10-4 M) responses were recorded. The groups were comparable in terms of age, gravida, parity, delivery type and gestational week (p>0.05). The homogenous distribution of telocytes in the mucosa and muscular layers of the control group, changed to heterogeneous localization the EP group. Immunohistochemical staining with vimentin, S100A, c-Kit and CD34, revealed increased telocyte counts in the muscular layer and serosa of the tubal tissues of EP. The frequency of the spontaneous contractions was higher in the control group (p<0.001); contrarily, the amplitude of the contractions was higher in ectopic pregnancies (p<0.001). Although the cumulative oxytocin dose-contraction curves were similar at all concentrations (p>0.05), the cumulative progesterone dose-relaxation curves exhibited higher relaxation response in the EP group at all concentrations (p<0.001). Increased telocyte count in the fallopian tube may decrease tubal motility and may affect the transfer of the blastocyst to the uterus and possibly contribute to the pathogenesis of EP.

Viable Allogeneic Mitochondria Transplantation Improves Gas Exchange and Alveolar-Capillary Permeability in Rats with Endotoxin-Induced Acute Lung Injuries.

Background: Acute lung injuries (ALI) cause disruption of the alveolar-capillary barrier and is the leading cause of death in critically ill patients. This study tested the hypothesis that the administration of freshly isolated viable allogeneic mitochondria can prevent alveolar-capillary barrier injuries at the endothelial level, as mitochondrial dysfunction of the pulmonary endothelium is a critical aspect of ALI progression.Methods: ALI was induced by intratracheal lipopolysaccharide instillation (LPS, 1mg/kg) in anesthetized rats. Mitochondria (100 µg) were isolated from the freshly harvested soleus muscles of naïve rats and stained with a green fluorescence MitoTracker™ dyne. A mitochondria or placebo solution was randomly administered into the jugular veins of the rats at 2 h and 4 h after ALI induction. An arterial blood gas analysis was done 20 h later. The animals were then sacrificed and lung tissues were harvested for analysis.Results: An IVIS Spectrum imaging system was used to obtain ex vivo heart-lung block images and track the enhancement of MitoTracker™ fluorescence in the lungs. Mitochondria transplantation significantly improved arterial oxygen contents (PaO2 and SaO2) and reduced CO2 tension in rats with ALI. Animals with mitochondrial transplants had significantly higher ATP concentrations in their lung tissues. Allogeneic mitochondria transplantation preserved alveolar-capillary barrier function, as shown by a reduction in protein levels in the bronchoalveolar lavage fluid and decreased extravasated Evans blue dyne and hemoglobin content in lung tissues. In addition, relaxation responses to acetylcholine and eNOS expression were potentiated in injured pulmonary arteries and inflammatory cells infiltration into lung tissue was reduced following mitochondrial transplantation.Conclusions: Transplantation of viable mitochondria protects the integrity of endothelial lining of the alveolar-capillary barrier, thereby improving gas exchange during the acute stages of endotoxin-induced ALI. However, the long-term effects of mitochondrial transplantation on pulmonary function recovery after ALI requires further investigation.