1.Hesperetin Relaxes Depolarizing Contraction in Human Umbilical Vein by Inhibiting L-Type Ca2+ Channel.
Kritsana TIPCOME ; Wattana B WATANAPA ; Katesirin RUAMYOD
Chinese journal of integrative medicine 2025;31(5):412-421
OBJECTIVE:
To study hesperetin-induced vasorelaxation after depolarizing contraction in human umbilical veins (HUVs) to elucidate the role of L-type Ca2+ channel (LTCC) and related signaling pathway.
METHODS:
Isometric tension recording was performed in HUV rings pre-contracted with K+. Hesperetin relaxing mechanism was investigated using a LTCC opener (BayK8644) and blockers of cyclic nucleotides and phosphodiesterases (PDEs). Whole-cell patch-clamping in A7r5 cells, a rat vascular smooth muscle cell line, was performed to study the effect of hesperetin on LTCC current.
RESULTS:
After depolarizing precontraction, hesperetin induced HUV relaxation concentration-dependently and endothelium-independently; 1 mmol/L hesperetin reduced denuded HUV ring tension by 68.7% ± 4.3% compared to matching vehicle, osmolality, and time controls (P<0.0001). Importantly, hesperetin competitively inhibited BayK8644-induced contraction, shifting the half maximal effective concentration of BayK8644 response from 1.08 nmol/L [95% confidence interval (CI) 0.49-2.40] in vehicle control to 11.30 nmol/L (95% CI 5.45-23.41) in hesperetin (P=0.0001). Moreover, hesperetin elicited further vasorelaxation in denuded HUV rings pretreated with inhibitors of soluble guanylyl cyclase, adenylyl cyclase, PDE3, PDE4, and PDE5 (P<0.01), while rings pretreated with PDE1 inhibitors could not be relaxed by hesperetin (P>0.05). However, simultaneously applying inhibitors of soluble guanylyl cyclase and adenylyl cyclase could not inhibit hesperetin's effect (P>0.05). In whole-cell patch-clamping, hesperetin rapidly decreased LTCC current in A7r5 cells to 66.7% ± 5.8% (P=0.0104).
CONCLUSIONS
Hesperetin diminishes depolarizing contraction of human vascular smooth muscle through inhibition of LTCC, and not cyclic nucleotides nor PDEs. Our evidence supports direct LTCC interaction and provides additional basis for the use of hesperetin and its precursor hesperidin as vasodilators and may lead to future vasodilator drug development as a treatment alternative for cardiovascular diseases.
Hesperidin/pharmacology*
;
Humans
;
Calcium Channels, L-Type/metabolism*
;
Umbilical Veins/physiology*
;
Muscle Contraction/drug effects*
;
Animals
;
Rats
;
Calcium Channel Blockers/pharmacology*
;
Vasodilation/drug effects*
;
Muscle Relaxation/drug effects*
2.Therapeutic Effect of Yu Melody Relaxation Training Combined with Jianpi Jieyu Decoction in Insomnia Patients: A Randomized Controlled Trial.
Hao-Yu PANG ; Xu CHEN ; Ling-Yun XI ; Qian-Lin JIA ; Yang BAI ; Jing CAO ; Xia HONG
Chinese journal of integrative medicine 2025;31(4):291-298
OBJECTIVE:
To evaluate the therapeutic effect of Yu Melody relaxation training (YMRT) combined with Jianpi Jieyu Decoction (JJD) in treating patients with insomnia disorders (ID).
METHODS:
In this randomized controlled study, 94 ID patients were included from Xiyuan Hospital, China Academy of Chinese Medical Sciences from September 2022 to January 2024. They were randomly assigned to the YMRT group (47 cases, YMRT plus JJD) and the control group (47 cases, oral JJD) using a random number table. Both treatment administrations lasted for 4 weeks, with a 2-week follow-up. The primary outcome was change in Insomnia Severity Index (ISI) scores from baseline to 4 weeks of intervention. Secondary outcomes included ISI response at week 4, as well as ISI, Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder 7-item (GAD-7) scores at baseline and weeks 1, 2, 3, 4, and 6. Additionally, Pittsburgh Sleep Quality Index (PSQI) scores were evaluated at baseline and weeks 4 and 6. Adverse events (AEs) were recorded and compared between groups.
RESULTS:
Five patients in each group did not complete the protocol requirements. The overall dropout rate was 10.64%. The full analysis set included all 47 cases in each group. The ISI score decreased significantly at week 4 from baseline in the YMRT group compared with the control group, with a between-group difference of -3.2 points [95% confidence interval (CI): -5.08 to -1.34; P<0.05]. The ISI response at week 4 in the YMRT group was significantly higher than that in the control group (85.11% vs. 51.06%), with a between-group difference of 34.05% (95% CI: 13.77% to 50.97%; P<0.05). At week 6, the YMRT group demonstrated greater reductions from baseline than the control group, with between-group differences of -2.1 points (-95% CI: -3.49 to -0.64; P<0.05) for PHQ-9 scores, -3.5 points (95% CI: -5.21 to -1.85; P<0.05) for PSQI scores, and -1.9 points (95% CI: -3.47 to -0.28; P<0.05) for GAD-7 scores. Moreover, at weeks 4 and 6, the ISI and PSQI scores in the YMRT group were significantly lower than those in the control group (P<0.05); and at week 6, the PHQ-9 score in the YMRT group was significantly lower (P<0.05). There was no significant difference in the incidence rates of AEs between the two groups (8.51% vs. 4.26%, P>0.05).
CONCLUSIONS
YMRT combined with oral JJD could improve sleep quality and alleviate depressive and anxiety symptoms in patients with ID. This combined therapy was effective and safe, and its effect was superior to oral JJD alone. (Registration No. ChiCTR2200063884).
Humans
;
Sleep Initiation and Maintenance Disorders/drug therapy*
;
Drugs, Chinese Herbal/therapeutic use*
;
Male
;
Female
;
Relaxation Therapy/methods*
;
Middle Aged
;
Adult
;
Treatment Outcome
;
Combined Modality Therapy
3.Effects of forest bathing on pre-hypertensive and hypertensive adults: a review of the literature.
Katherine Ka-Yin YAU ; Alice Yuen LOKE
Environmental Health and Preventive Medicine 2020;25(1):23-23
The aim in this literature review was (1) to explore the physiologically and psychologically therapeutic benefits of forest bathing on adults suffering from pre-hypertension or hypertension, and (2) to identify the type, duration, and frequency of an effective forest bathing intervention in the management of pre-hypertension and hypertension, so as to provide directions for future interventions or research. The electronic databases PubMed, Cochrane Library, CINAHL, PsyINFO, and the China Academic Journals (CAJ) offered through the Full-text Database (CNKI) were searched for relevant studies published from the inception of the databases to April 2019. Of the 364 articles that were identified, 14 met the criteria for inclusion in this review. The synthesis of the findings in the included studies revealed that forest bathing interventions were effective at reducing blood pressure, lowering pulse rate, increasing the power of heart rate variability (HRV), improving cardiac-pulmonary parameters, and metabolic function, inducing a positive mood, reducing anxiety levels, and improving the quality of life of pre-hypertensive or hypertensive participants. Forest walking and forest therapy programs were the two most effective forest bathing interventions. Studies reported that practicing a single forest walking or forest therapy program can produce short-term physiological and psychological benefits. It is concluded that forest bathing, particularly forest walking and therapy, has physiologically and psychologically relaxing effects on middle-aged and elderly people with pre-hypertension and hypertension.
Adult
;
Aged
;
Aged, 80 and over
;
Female
;
Forests
;
Humans
;
Hypertension
;
prevention & control
;
Male
;
Middle Aged
;
Prehypertension
;
prevention & control
;
Relaxation Therapy
;
statistics & numerical data
;
Young Adult
4.Efficacy of internet-based integrated intervention on depression and anxiety symptoms in patients with COVID-19.
Ning WEI ; Bo-Chao HUANG ; Shao-Jia LU ; Jian-Bo HU ; Xiao-Yi ZHOU ; Chan-Chan HU ; Jing-Kai CHEN ; Jin-Wen HUANG ; Shu-Guang LI ; Zheng WANG ; Dan-Dan WANG ; Yi XU ; Shao-Hua HU
Journal of Zhejiang University. Science. B 2020;21(5):400-404
Public health crises, such as the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since Dec. 2019, are widely acknowledged as severe traumatic events that impose threats not only because of physical concerns but also because of the psychological distress of infected patients. We designed an internet-based integrated intervention and evaluated its efficacy on depression and anxiety symptoms in patients infected by SARS-CoV-2.
Adult
;
Anxiety
;
therapy
;
Betacoronavirus
;
Cell Phone
;
China
;
Coronavirus Infections
;
psychology
;
Depression
;
therapy
;
Female
;
Humans
;
Internet
;
Male
;
Middle Aged
;
Mindfulness
;
Pandemics
;
Pneumonia, Viral
;
psychology
;
Prospective Studies
;
Psychological Distress
;
Relaxation Therapy
;
Self Care
;
methods
5.Evaluation of Renal Pathophysiological Processes Induced by an Iodinated Contrast Agent in a Diabetic Rabbit Model Using Intravoxel Incoherent Motion and Blood Oxygenation Level-Dependent Magnetic Resonance Imaging
Yongfang WANG ; Xin ZHANG ; Bin WANG ; Yang XIE ; Yi WANG ; Xuan JIANG ; Rongjia WANG ; Ke REN
Korean Journal of Radiology 2019;20(5):830-843
OBJECTIVE: To examine the potential of intravoxel incoherent motion (IVIM) and blood oxygen level-dependent (BOLD) magnetic resonance imaging for detecting renal changes after iodinated contrast-induced acute kidney injury (CI-AKI) development in a diabetic rabbit model. MATERIALS AND METHODS: Sixty-two rabbits were randomized into 2 groups: diabetic rabbits with the contrast agent (DCA) and healthy rabbits with the contrast agent (NCA). In each group, 6 rabbits underwent IVIM and BOLD imaging at 1 hour, 1 day, 2 days, 3 days, and 4 days after an iohexol injection while 5 rabbits were selected to undergo blood and histological examinations at these specific time points. Iohexol was administrated at a dose of 2.5 g I/kg of body weight. Further, the apparent transverse relaxation rate (R2*), average pure molecular diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) were calculated. RESULTS: The D and f values of the renal cortex (CO) and outer medulla (OM) were significantly decreased compared to baseline values in the 2 groups 1 day after the iohexol injection (p < 0.05). A marked reduction in the D* values for both the CO and OM was also observed after 1 hour in each group (p < 0.05). In the OM, a persistent elevation of the R2* was detected for 4 days in the DCA group (p < 0.05). Histopathological changes were prominent, and the pathological features of CI-AKI aggravated in the DCA group until day 4. The D, f, and R2* values significantly correlated with the histological damage scores, hypoxia-inducible transcription factor-1α expression scores, and serum creatinine levels. CONCLUSION: A combination of IVIM and BOLD imaging may serve as a noninvasive method for detecting and monitoring CI-AKI in the early stages in the diabetic kidney.
Acute Kidney Injury
;
Body Weight
;
Creatinine
;
Diffusion
;
Iohexol
;
Kidney
;
Magnetic Resonance Imaging
;
Methods
;
Oxygen
;
Perfusion
;
Rabbits
;
Relaxation
;
Vascular Endothelial Growth Factor A
6.Is Upright Integrated Relaxation Pressure Useful in Diagnosis of Esophagogastric Junction Outflow Obstruction?
The Korean Journal of Gastroenterology 2019;73(4):242-244
No abstract available.
Diagnosis
;
Esophagogastric Junction
;
Relaxation
7.Assessment of Clinical Outcomes after Peroral Endoscopic Myotomy via Esophageal Distensibility Measurements with the Endoluminal Functional Lumen Imaging Probe.
In Kyung YOO ; Sang Ah CHOI ; Won Hee KIM ; Sung Pyo HONG ; Ozlem Ozer CAKIR ; Joo Young CHO
Gut and Liver 2019;13(1):32-39
BACKGROUND/AIMS: Endoluminal functional lumen imaging probe (EndoFLIP) is a modality that enables clinicians to measure volume-controlled distension of the esophagus. This study aimed to assess the utility of EndoFLIP in patients who had achalasia treated with peroral endoscopic myotomy (POEM). We hypothesized that improvement in the distensibility index (DI) is correlated with the postoperative clinical outcome of POEM. METHODS: Patients who underwent POEM for achalasia at Cha Bundang Medical Center were included. Physiological measurements of the lower esophageal sphincter (LES) pressure before and after POEM were assessed using EndoFLIP. Patients’ symptoms were recorded using the Eckardt score. RESULTS: A total of 52 patients with achalasia were included in this study. Patients with a post-POEM DI below 7 (30 or 40 mL) had a significantly higher rate of incomplete response after POEM (p=0.001). Changes in LES pressure or integrated relaxation pressure after POEM were also significantly associated with an incomplete response (p=0.026 and p=0.016, respectively). Multivariate analysis showed that post-POEM DI < 7 was the most important predictor of an incomplete response after POEM (p=0.004). CONCLUSIONS: Lower post-POEM DI values were associated with an incomplete post-POEM response. Therefore, post-POEM DI at the esophagogastric junction using EndoFLIP is a useful index for predicting the clinical outcome of POEM in patients with achalasia.
Esophageal Achalasia
;
Esophageal Sphincter, Lower
;
Esophagogastric Junction
;
Esophagus
;
Humans
;
Multivariate Analysis
;
Relaxation
;
Treatment Outcome
8.Mechanism of Mindfulness-Based Intervention and Neurobiological Basis
Journal of the Korean Society of Biological Therapies in Psychiatry 2019;25(2):85-94
Mindfulness is a process in which all thoughts, feelings, sensations, and all phenomena that happen to me are uncritically recognized as they are, so that they are eventually accepted and released without identifying or automatically responding to them. The clinical effects of mindfulness-based therapy have already been demonstrated in several studies. However, consistent results have not been reported for the mechanism of mindfulness-based treatment. Thus, this review aimed to describe a systematic review of the literature and research on the mechanisms of mindfulness-based interventions. Experienced meditators showed a physiological change in a ‘wakeful hypometabolic state’ during mindfulness meditation. In mindfulness meditation, it is known that certain areas other than brain activation during relaxation are additionally activated, particularly activation of fronto-limbic and fronto-parietal neural networks. The psychological mechanisms include meta-cognitive awareness, emotion regulation, reduction of automatic and self-referential thinking, concentration control, self-compassion, improvement of value clarification and self-regulation, exposure, extinction, and reconsolidation. Of the brain regions with changes in activity associated with mindfulness meditation, prefrontal cortex, the default mode network including cortical midline structures were associated with emotion regulation, concentration control, and reduction of automatic and self-referential thinking. In addition, brain regions associated with mindfulness meditation have been reported in the hippocampus, amygdala, and medical frontal cortices associated with memory reconsolidation and fear extinction. Thus, mindfulness-based interventions have a psychological and neurobiological effect with a special mechanism different from other psychological interventions, so that mindfulness based intervention can be an effective therapeutic intervention with a different mechanism from other psychological techniques.
Amygdala
;
Brain
;
Frontal Lobe
;
Hippocampus
;
Meditation
;
Memory
;
Mindfulness
;
Prefrontal Cortex
;
Psychological Techniques
;
Relaxation
;
Self-Control
;
Sensation
;
Thinking
9.Management of Achalasia: Expert Consensus Statements
The Korean Journal of Gastroenterology 2019;73(5):294-298
Achalasia is a motility disorder of the esophagus characterized by absence of peristalsis and failure of relaxation of lower esophagus sphincter. The introduction of high resolution manometry (HRM) and per-oral endoscopic myotomy (POEM) has made a new chapter in diagnosis and treatment of achalasia. HRM allows classify according to the subtype of achalasia, and help predict prognosis and therapeutic response. POEM is a minimally invasive, effective option for treating achalasia. The management of achalasia required tailored application of various therapies such as botox injection, pneumatic balloon dilatation, POEM, or Heller's myotomy. In this review, we state the important aspects of diagnosis as well as management of achalasia.
Consensus
;
Diagnosis
;
Dilatation
;
Esophageal Achalasia
;
Esophagus
;
Manometry
;
Peristalsis
;
Prognosis
;
Relaxation
10.Early Phase of Achalasia Manifested as an Esophageal Subepithelial Tumor
Jong Hwa LEE ; Young Jae LEE ; Jong Myeong LEE ; Myoung Jin JU ; Min A YANG ; Myung Woo CHOI ; So Hee YUN
The Korean Journal of Gastroenterology 2019;74(2):110-114
The Chicago classification (CC) defines an esophagogastric junction outflow obstruction (EGJOO) as the presence of several instances of intact or weak peristalsis, elevated median integrated relaxation pressure above 15 mmHg, and a discrepancy from the criteria of achalasia. The revised CC addresses the potential etiology of EGJOO, including the early forms of achalasia, mechanical obstruction, esophageal wall stiffness, or manifestation of hiatal hernia. A 58-year-old woman visited the Presbyterian Medical Center with swallowing difficulty. The patient underwent a high resolution manometry (HRM) examination and was diagnosed with EGJOO. Chest CT was performed to exclude a mechanical obstruction as a cause, and CT revealed a subepithelial tumor (SET) at the upper part of the esophagogastric junction. Therefore, laparoscopic surgery was performed and eccentric muscular hypertrophy of the distal esophagus was observed. Longitudinal myotomy and Dor fundoplication were also performed. The histology findings of the surgical specimens were consistent with achalasia. This paper reports a case of early achalasia that was finally diagnosed by the histology findings, but was initially diagnosed as EGJOO using HRM and misdiagnosed as SET in the image study.
Classification
;
Deglutition
;
Esophageal Achalasia
;
Esophagogastric Junction
;
Esophagus
;
Female
;
Fundoplication
;
Hernia, Hiatal
;
Humans
;
Hypertrophy
;
Laparoscopy
;
Manometry
;
Middle Aged
;
Peristalsis
;
Protestantism
;
Relaxation
;
Tomography, X-Ray Computed

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