1.Shank3 Overexpression Leads to Cardiac Dysfunction in Mice by Disrupting Calcium Homeostasis in Cardiomyocytes
Tae Hee KO ; Yoonhee KIM ; Chunmei JIN ; Byeongil YU ; Minju LEE ; Phuong Kim LUONG ; Tran Nguyet TRINH ; Yeji YANG ; Hyojin KANG ; Yinhua ZHANG ; Ruiying MA ; Kwangmin YOO ; Jungmin CHOI ; Jin Young KIM ; Sun-Hee WOO ; Kihoon HAN ; Jong-Il CHOI
Korean Circulation Journal 2025;55(2):100-117
Background and Objectives:
SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms.
Methods:
Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes.
Results:
The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes.
Conclusions
This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.
2.Shank3 Overexpression Leads to Cardiac Dysfunction in Mice by Disrupting Calcium Homeostasis in Cardiomyocytes
Tae Hee KO ; Yoonhee KIM ; Chunmei JIN ; Byeongil YU ; Minju LEE ; Phuong Kim LUONG ; Tran Nguyet TRINH ; Yeji YANG ; Hyojin KANG ; Yinhua ZHANG ; Ruiying MA ; Kwangmin YOO ; Jungmin CHOI ; Jin Young KIM ; Sun-Hee WOO ; Kihoon HAN ; Jong-Il CHOI
Korean Circulation Journal 2025;55(2):100-117
Background and Objectives:
SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms.
Methods:
Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes.
Results:
The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes.
Conclusions
This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.
3.Shank3 Overexpression Leads to Cardiac Dysfunction in Mice by Disrupting Calcium Homeostasis in Cardiomyocytes
Tae Hee KO ; Yoonhee KIM ; Chunmei JIN ; Byeongil YU ; Minju LEE ; Phuong Kim LUONG ; Tran Nguyet TRINH ; Yeji YANG ; Hyojin KANG ; Yinhua ZHANG ; Ruiying MA ; Kwangmin YOO ; Jungmin CHOI ; Jin Young KIM ; Sun-Hee WOO ; Kihoon HAN ; Jong-Il CHOI
Korean Circulation Journal 2025;55(2):100-117
Background and Objectives:
SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms.
Methods:
Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes.
Results:
The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes.
Conclusions
This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.
4.Shank3 Overexpression Leads to Cardiac Dysfunction in Mice by Disrupting Calcium Homeostasis in Cardiomyocytes
Tae Hee KO ; Yoonhee KIM ; Chunmei JIN ; Byeongil YU ; Minju LEE ; Phuong Kim LUONG ; Tran Nguyet TRINH ; Yeji YANG ; Hyojin KANG ; Yinhua ZHANG ; Ruiying MA ; Kwangmin YOO ; Jungmin CHOI ; Jin Young KIM ; Sun-Hee WOO ; Kihoon HAN ; Jong-Il CHOI
Korean Circulation Journal 2025;55(2):100-117
Background and Objectives:
SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms.
Methods:
Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes.
Results:
The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes.
Conclusions
This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.
5.Effectiveness and safety of electroacupuncture analgesia in controlling intraoperative pain and hemodynamics during total thyroidectomy: A randomized controlled trial
Dong Phuong Tran ; Quoc Dung Nguyen ; Ninh Khac Nguyen ; Van Hong Pham
Journal of Traditional Chinese Medical Sciences 2024;11(2):165-171
Objective:
To evaluate the effectiveness and safety of electroacupuncture in conjunction with additional medications in providing analgesia and stabilizing hemodynamic parameters during total thyroidectomy.
Methods:
This randomized controlled trial included 100 patients who underwent a total thyroidectomy between October 2022 and October 2023 at the Vietnam National Hospital of Acupuncture. The patients were randomized into two groups. The electroacupuncture analgesia (EA) group received EA stimulation at five acupuncture points: Hegu (LI 4), Neiguan (PC 6), Shuitu (ST 10), Quepen (ST 12), and Yifeng (SJ 17), while the control group received a bilateral superficial cervical plexus block. Primary outcomes included the level of analgesia and perioperative vital signs in both groups. Additionally, pain thresholds and serum β-endorphin levels were measured before and after electroacupuncture in the EA group.
Results:
Complete analgesia (Level A) was attained in 86% and 76% of the patients in the EA and control groups, respectively, with no significant difference between the two groups (P = 1.00). In the EA group, the mean pain threshold after receiving EA doubled (648.7 (77.4) g/s vs. 305.3 (45.3) g/s, P < .001), and the mean serum β-endorphin level increased by approximately 13.5 pg/mL (P < .001). All patients remained hemodynamically stable throughout the surgery.
Conclusion
EA, in conjunction with additional medications that stimulate five acupuncture points, LI 4, PC 6, ST 10, ST 12, and SJ 17, was well tolerated and effectively maintained a suitable level of analgesia and hemodynamic stability during total thyroidectomy.
6.Active case finding to detect symptomatic and subclinical pulmonary tuberculosis disease: implementation of computer-aided detection for chest radiography in Viet Nam
Anh L Innes ; Andres Martinez ; Gia Linh Hoang ; Thi Bich Phuong Nguyen ; Viet Hien Vu ; Tuan Ho Thanh Luu ; Thi Thu Trang Le ; Victoria Lebrun ; Van Chinh Trieu ; Nghi Do Bao Tran ; Nhi Dinh ; Huy Minh Pham ; Van Luong Dinh ; Binh Hoa Nguyen ; Thi Thanh Huyen Truong ; Van Cu Nguyen ; Viet Nhung Nguyen ; Thu Hien Mai
Western Pacific Surveillance and Response 2024;15(4):14-25
Objective: In Viet Nam, tuberculosis (TB) prevalence surveys revealed that approximately 98% of individuals with pulmonary TB have TB-presumptive abnormalities on chest radiographs, while 32% have no TB symptoms. This prompted the adoption of the “Double X” strategy, which combines chest radiographs and computer-aided detection with GeneXpert testing to screen for and diagnose TB among vulnerable populations. The aim of this study was to describe demographic, clinical and radiographic characteristics of symptomatic and asymptomatic Double X participants and to assess multilabel radiographic abnormalities on chest radiographs, interpreted by computer-aided detection software, as a possible tool for detecting TB-presumptive abnormalities, particularly for subclinical TB.
Methods: Double X participants with TB-presumptive chest radiographs and/or TB symptoms and known risks were referred for confirmatory GeneXpert testing. The demographic and clinical characteristics of all Double X participants and the subset with confirmed TB were summarized. Univariate and multivariable logistic regression modelling was used to evaluate associations between participant characteristics and subclinical TB and between computer-aided detection multilabel radiographic abnormalities and TB.
Results: From 2020 to 2022, 96 631 participants received chest radiographs, with 67 881 (70.2%) reporting no TB symptoms. Among 1144 individuals with Xpert-confirmed TB, 51.0% were subclinical. Subclinical TB prevalence was higher in older age groups, non-smokers, those previously treated for TB and the northern region. Among 11 computer-aided detection multilabel radiographic abnormalities, fibrosis was associated with higher odds of subclinical TB.
Discussion: In Viet Nam, Double X community case finding detected pulmonary TB, including subclinical TB. Computer-aided detection software may have the potential to identify subclinical TB on chest radiographs by classifying multilabel radiographic abnormalities, but further research is needed.
7.Sesquiterpenes from Curcuma zedoaria (Christm.) Rosc. Rhizomes and Their Alpha-Glucosidase Inhibitory Effects
Ngan Thi TRAN ; Phuong Nguyen Thi THU ; Mai-Ngan Thi LE ; Quynh-Mai Thi NGO
Natural Product Sciences 2024;30(4):300-303
Curcuma zedoaria (Christm.) Rosc. is a popular traditional herb to treat digestive disorders in Asian tropical countries. Previous studies indicated the presence of sesquiterpenoids, diterpenoids, and curcuminoids with various bioactivities. To enrich the phytocomposition data of this plant, this investigation was conducted.The dried rhizomes of C. zedoaria were collected in Hai Phong City (Vietnam), extracted with methanol and fractionated with n-hexane, CH2Cl2 , and EtOAc. Compounds were isolated from n-hexane soluble fraction by open column chromatography combined with thin layer chromatography from fraction n-hexane. Their chemical structures were elucidated by 1D, and 2D NMR spectra and comparison with reported data. As a result, a phytochemical investigation was conducted to isolate six sesquiterpenes from C. zedoaria. Their chemical structures were elucidated to be curcumenol (1), procurcumenol (2), neoprocurcumenol (3), 13-hydroxygermacrone (4), zederone (5), and curcumalactone (6). Among isolated compounds, compounds 1, 2, 4, and 5 were reported from C. zedoaria. Meanwhile, neoprocurcumenol (3) and curcumalactone (6) are isolated from this species for the first time. Compound 5 exhibited a mild inhibitory effect on α-glucosidase with an IC50 of 99.45 ± 0.50 μg/mL.
8.Sesquiterpenes from Curcuma zedoaria (Christm.) Rosc. Rhizomes and Their Alpha-Glucosidase Inhibitory Effects
Ngan Thi TRAN ; Phuong Nguyen Thi THU ; Mai-Ngan Thi LE ; Quynh-Mai Thi NGO
Natural Product Sciences 2024;30(4):300-303
Curcuma zedoaria (Christm.) Rosc. is a popular traditional herb to treat digestive disorders in Asian tropical countries. Previous studies indicated the presence of sesquiterpenoids, diterpenoids, and curcuminoids with various bioactivities. To enrich the phytocomposition data of this plant, this investigation was conducted.The dried rhizomes of C. zedoaria were collected in Hai Phong City (Vietnam), extracted with methanol and fractionated with n-hexane, CH2Cl2 , and EtOAc. Compounds were isolated from n-hexane soluble fraction by open column chromatography combined with thin layer chromatography from fraction n-hexane. Their chemical structures were elucidated by 1D, and 2D NMR spectra and comparison with reported data. As a result, a phytochemical investigation was conducted to isolate six sesquiterpenes from C. zedoaria. Their chemical structures were elucidated to be curcumenol (1), procurcumenol (2), neoprocurcumenol (3), 13-hydroxygermacrone (4), zederone (5), and curcumalactone (6). Among isolated compounds, compounds 1, 2, 4, and 5 were reported from C. zedoaria. Meanwhile, neoprocurcumenol (3) and curcumalactone (6) are isolated from this species for the first time. Compound 5 exhibited a mild inhibitory effect on α-glucosidase with an IC50 of 99.45 ± 0.50 μg/mL.
9.Sesquiterpenes from Curcuma zedoaria (Christm.) Rosc. Rhizomes and Their Alpha-Glucosidase Inhibitory Effects
Ngan Thi TRAN ; Phuong Nguyen Thi THU ; Mai-Ngan Thi LE ; Quynh-Mai Thi NGO
Natural Product Sciences 2024;30(4):300-303
Curcuma zedoaria (Christm.) Rosc. is a popular traditional herb to treat digestive disorders in Asian tropical countries. Previous studies indicated the presence of sesquiterpenoids, diterpenoids, and curcuminoids with various bioactivities. To enrich the phytocomposition data of this plant, this investigation was conducted.The dried rhizomes of C. zedoaria were collected in Hai Phong City (Vietnam), extracted with methanol and fractionated with n-hexane, CH2Cl2 , and EtOAc. Compounds were isolated from n-hexane soluble fraction by open column chromatography combined with thin layer chromatography from fraction n-hexane. Their chemical structures were elucidated by 1D, and 2D NMR spectra and comparison with reported data. As a result, a phytochemical investigation was conducted to isolate six sesquiterpenes from C. zedoaria. Their chemical structures were elucidated to be curcumenol (1), procurcumenol (2), neoprocurcumenol (3), 13-hydroxygermacrone (4), zederone (5), and curcumalactone (6). Among isolated compounds, compounds 1, 2, 4, and 5 were reported from C. zedoaria. Meanwhile, neoprocurcumenol (3) and curcumalactone (6) are isolated from this species for the first time. Compound 5 exhibited a mild inhibitory effect on α-glucosidase with an IC50 of 99.45 ± 0.50 μg/mL.
10.Sesquiterpenes from Curcuma zedoaria (Christm.) Rosc. Rhizomes and Their Alpha-Glucosidase Inhibitory Effects
Ngan Thi TRAN ; Phuong Nguyen Thi THU ; Mai-Ngan Thi LE ; Quynh-Mai Thi NGO
Natural Product Sciences 2024;30(4):300-303
Curcuma zedoaria (Christm.) Rosc. is a popular traditional herb to treat digestive disorders in Asian tropical countries. Previous studies indicated the presence of sesquiterpenoids, diterpenoids, and curcuminoids with various bioactivities. To enrich the phytocomposition data of this plant, this investigation was conducted.The dried rhizomes of C. zedoaria were collected in Hai Phong City (Vietnam), extracted with methanol and fractionated with n-hexane, CH2Cl2 , and EtOAc. Compounds were isolated from n-hexane soluble fraction by open column chromatography combined with thin layer chromatography from fraction n-hexane. Their chemical structures were elucidated by 1D, and 2D NMR spectra and comparison with reported data. As a result, a phytochemical investigation was conducted to isolate six sesquiterpenes from C. zedoaria. Their chemical structures were elucidated to be curcumenol (1), procurcumenol (2), neoprocurcumenol (3), 13-hydroxygermacrone (4), zederone (5), and curcumalactone (6). Among isolated compounds, compounds 1, 2, 4, and 5 were reported from C. zedoaria. Meanwhile, neoprocurcumenol (3) and curcumalactone (6) are isolated from this species for the first time. Compound 5 exhibited a mild inhibitory effect on α-glucosidase with an IC50 of 99.45 ± 0.50 μg/mL.


Result Analysis
Print
Save
E-mail