Noninvasive right ventricular work in patients with atrial septal defects: a proof-of-concept study.

BACKGROUND: Noninvasive right ventricular (RV) myocardial work (RVMW) determined by echocardiography is a novel indicator used to estimate RV systolic function. To date, the feasibility of using RVMW has not been verified in assessing RV function in patients with atrial septal defect (ASD). METHODS: Noninvasive RVMW was analysed in 29 ASD patients (median age, 49 years; 21% male) and 29 age- and sex-matched individuals without cardiovascular disease. The ASD patients underwent echocardiography and right heart catheterization (RHC) within 24 h. RESULTS: The RV global work index (RVGWI), RV global constructive work (RVGCW), and RV global wasted work (RVGWW) were significantly higher in the ASD patients than in the controls, while there was no significant difference in RV global work efficiency (RVGWE). RV global longitudinal strain (RV GLS), RVGWI, RVGCW, and RVGWW demonstrated significant correlations with RHC-derived stroke volume (SV) and SV index. The RVGWI (area under receiver operating characteristic curve [AUC] = 0.895), RVGCW (AUC = 0.922), and RVGWW (AUC = 0.870) could be considered good predictors of ASD and were superior to RV GLS (AUC = 0.656). CONCLUSION: The RVGWI, RVGCW, and RVGWW could be used to assess RV systolic function and are correlated with RHC-derived SV and SV index in patients with ASD.

The non-invasive echocardiographic assessment of right ventricular myocardial work in a healthy population.

BACKGROUND: Non-invasive right ventricular (RV) myocardial work (RVMW) is the latest indicator used to assess RV function. Nevertheless, the physiological determinants of RVMW have not been studied, and reference ranges for normal RVMW indices have yet to be established. METHODS: A total of 263 healthy volunteers (median age: 34 years, males: 38%) were prospectively enrolled. RVMW indices were analysed by an RV pressure-strain loop (RVPSL) in specific software. RESULTS: The lowest values of the RVMW indices in males and females were 133 mmHg% and 206 mmHg% for RV global work index (RVGWI), 165 mmHg% and 241 mmHg% for RV global constructive work (RVGCW) and 78% and 83% for RV global work efficiency (RVGWE), respectively. The highest values for RV global wasted work (RVGWW) in males and females were 67 mmHg% and 69 mmHg%, respectively. RVGWI and RVGCW were significantly lower in males than those in females. RVGWW significantly increased with age in males and females. RVGWE significantly decreased with age in females. Multivariable analysis revealed that RVGWI, RVGCW and RVGWE increased as pulmonary artery systolic pressure (PASP) increased. CONCLUSIONS: Normal reference values of non-invasive RVMW were obtained by echocardiography. Quantitative data on RVMW could be essential in clinical work and clinical experiments.

Piperlongumine inhibits proliferation and oncogenic MYCN expression in chemoresistant metastatic retinoblastoma cells directly and through extracellular vesicles.

Ocular retinoblastoma malignancies, which develop into metastatic phenotypes, result in poor prognosis and survival for infant and child patients. To improve the prognosis of metastatic retinoblastoma, it is important to identify novel compounds with less toxic side effects and higher therapeutic efficacy compared to existing chemotherapeutics. Piperlongumine (PL), a neuroprotective, plant-derived compound has been explored for its anticancer activities both in vitro and in vivo. Here, we analyze the potential efficacy of PL for metastatic retinoblastoma cell treatment. Our data reveal that PL treatment significantly inhibits cell proliferation in metastatic retinoblastoma Y79 cells compared to the commonly used retinoblastoma chemotherapeutic drugs carboplatin, etoposide, and vincristine. PL treatment also significantly increases cell death compared to treatment with other chemotherapeutic drugs. PL-induced cell-death signaling was associated with significantly higher caspase 3/7 activities and greater loss of mitochondrial membrane potential. PL was also internalized into Y79 cells with an estimated concentration of 0.310pM and expression analysis revealed reduced MYCN oncogene levels. We next examined extracellular vesicles derived from PL-treated Y79 cells. Extracellular vesicles in other cancers are pro-oncogenic, mediating systemic toxicities via the encapsulation of chemotherapeutic drugs. Within metastatic Y79 EV samples, an estimated PL concentration of 0.026pM was detected. PL treatment significantly downregulated Y79 EV cargo of the oncogene MYCN transcript. Interestingly, non-PL-treated Y79 cells incubated with EVs from PL-treated cells exhibited significantly reduced cell growth. These findings indicate that in metastatic Y79 cells, PL exhibits potent anti-proliferation effects and oncogene downregulation. Importantly, PL is also incorporated into extracellular vesicles released from treated metastatic cells with measurable anti-cancer effects on target cells at a distance from the site of primary treatment. The use of PL in the treatment of metastatic retinoblastoma may reduce primary tumor proliferation and inhibit metastatic cancer activity systemically via extracellular vesicle circulation.

Dynamic assessment of the tricuspid annulus in a healthy Asian population: A four-dimensional echocardiography study.

BACKGROUND: Tricuspid annulus (TA) geometry and function reference values are limited, especially for Asian populations. We aimed to explore TA using four-dimensional echocardiography (4DE) in a healthy Asian population. METHODS: A total of 355 healthy Asian volunteers (median age 34 years; 52% males) were prospectively enrolled. TA geometry and function were analyzed using 4DE throughout the cardiac cycle. RESULTS: The TA area, perimeter, and dimensions were smallest at end systole (ES) and largest at late diastole (LD). Normal TA parameters at end diastole (ED) in different sex and age groups were obtained. TA areas, perimeters, and dimensions in males were significantly larger than those in females at ED; BSA-indexed perimeters and BSA-indexed dimensions in males were significantly smaller than those in females at ED. TA parameters correlated well with tricuspid valve (TV) tenting, right ventricle (RV), and right atrium (RA) parameters. CONCLUSIONS: Reference values of TA parameters were obtained by 4DE in an Asian population. Quantitative data on TA geometry and function are essential for TA pathology and therapeutics.

Echocardiographic reference ranges for noninvasive left ventricular 18-segment myocardial work index and work efficiency in a healthy Asian population.

BACKGROUND: Left ventricular (LV) myocardial work index (WI) and work efficiency (WE) have become the latest indicators for assessing LV function. Reference ranges for normal LV segmental WI and WE have not been established. METHODS: Four hundred eleven healthy Asian subjects (47% men, median age: 35 years) were enrolled prospectively. WI and WE were analysed using the LV pressure-strain loop (LVPSL) with specific software. RESULTS: WI and WE differed significantly between segments as well as between walls and levels of the left ventricle. The anteroseptal basal segment had the lowest WI and WE (1440 mmHg ± 324 and 92% [88-96], respectively) among the eighteen segments. Significant WI and WE differences were found between sexes and age groups. No correlation was observed between age groups and the average WI of any wall or level in men, while the average WI of several different walls and levels in women showed significant differences between age groups. The average WI of most walls and levels increased with age in women. No correlation was found between age groups and the average WE of any wall or level in either men or women. CONCLUSIONS: This study establishes the normal reference values of WI and WE of eighteen segments for clinical work and clinical experiments. There were significant differences in WI and WE between segments, levels, and walls of the normal left ventricle. Sex should be considered when analysing WI and WE. Age should be considered when analysing WI in women.

Impact on right ventricular performance in patients undergoing permanent pacemaker implantation: Left bundle branch pacing versus right ventricular septum pacing.

BACKGROUND: The novel method of left bundle branch pacing (LBBP) has been reported to achieve better electrical and mechanical synchrony in the left ventricle than conventional right ventricular pacing (RVP). However, its effects on right ventricle (RV) performance are still unknown. METHODS: Consecutive patients undergoing dual-chamber pacemaker (PM) implantation for sick sinus syndrome (SSS) with normal cardiac function and a narrow QRS complex were recruited for the study. The pacing characteristics and echocardiogram parameters were measured to evaluate RV function, interventricular and RV synchrony, and were compared between ventricular pacing-on and native-conduction modes. RESULTS: A total of 84 patients diagnosed with SSS and an indication for pacing therapy were enrolled. Forty-two patients (50%; mean age 65.50 ± 9.30 years; 35% male) underwent successful LBBP and 42 patients (50%; mean age 69.26 ± 10.08 years; 33% male) RVSP, respectively. Baseline characteristics were similar between the two groups. We found no significant differences in RV function [RV-FAC (Fractional Area Change)%, 47.13 ± 5.69 versus 48.60 ± 5.83, p = .069; Endo-GLS (Global Longitudinal Strain)%, -28.88 ± 4.94 versus -29.82 ± 5.35, p = .114; Myo-GLS%, -25.72 ± 4.75 versus -25.72 ± 5.21, p = .559; Free Wall St%, 27.40 ± 8.03 versus -28.71 ± 7.34, p = .304] between the native-conduction and LBBP capture modes, while the RVSP capture mode was associated with a significant reduction in the above parameters compared with the native-conduction mode (p < .0001). The interventricular synchrony in the LBBP group was also superior to the RVSP group significantly. CONCLUSION: LBBP is a pacing technique that seems to associate with a positive and protective impact on RV performance.

Correlations among noninvasive right ventricular myocardial work indices and the main parameters of systolic and diastolic functions.

BACKGROUND: Right ventricular (RV) myocardial work (RVMW) is the latest method used to assess RV function. To date, correlations among RVMW indices and RV systolic and diastolic functions have not been studied. METHODS: A total of 106 healthy volunteers (median age, 34 years; 46% male) were prospectively enrolled. RVMW indices were measured using the RV pressure-strain loop using specific software. The correlations among RVMW indices and other RV functions were analyzed. RESULTS: During the multivariate analysis, the RV global work index (RVGWI) was significantly correlated with RV global longitudinal strain (RV GLS) (p < .0001), pulmonary systolic artery pressure (PASP) (p < .0001), and tricuspid annular (TA) plane systolic excursion (TAPSE) (p = .036). RV global constructive work (RVGCW) was correlated with RV GLS (p < .0001) and PASP (p < .0001). RV global wasted work (RVGWW) was correlated with RV GLS (p = .008) and TA isovolumetric acceleration (TA IVA) (p = .008). RV global work efficiency (RVGWE) was correlated with RV GLS (p < .0001) and tissue Doppler (TD) RV myocardial performance index (TD RMPI) (p = .043). CONCLUSION: RVMW indices showed good correlations with RV myocardial systolic function.

New xanthones from Canscora lucidissima and their antioxidant and NO inhibitory activities.

Three new xanthone glycosides, canlucosides A - C (1 - 3), along with three known compounds (4 - 6), have been obtained and identified from the ethanol extract of Canscora lucidissima. Their structures were identified according to HR-ESI-MS, 1D, 2D NMR data, ECD measurements powered by molecular calculations and optical rotation values. Compound 6 (1-hydroxy-3,7,8-trmethoxyxanthone) was isolated from C. lucidissima for the first time. Five compounds (2-6) showed moderate antioxidant and NO inhibitory activities. Canlucosides B and C (2 and 3) showed significant antioxidant activity with IC50 values of 33.64 ± 5.60 µM and 36.63 ± 4.32 µM, respectively. Canlucoside B (2) possessed a significant NO inhibitory effect with an IC50 value 0.92 µM.

An online repository of solvation thermodynamic and structural maps of SARS-CoV-2 targets.

SARS-CoV-2 recently jumped species and rapidly spread via human-to-human transmission to cause a global outbreak of COVID-19. The lack of effective vaccine combined with the severity of the disease necessitates attempts to develop small molecule drugs to combat the virus. COVID19_GIST_HSA is a freely available online repository to provide solvation thermodynamic maps of COVID-19-related protein small molecule drug targets. Grid inhomogeneous solvation theory maps were generated using AmberTools cpptraj-GIST, 3D reference interaction site model maps were created with AmberTools rism3d.snglpnt and hydration site analysis maps were created using SSTMap code. The resultant data can be applied to drug design efforts: scoring solvent displacement for docking, rational lead modification, prioritization of ligand- and protein- based pharmacophore elements, and creation of water-based pharmacophores. Herein, we demonstrate the use of the solvation thermodynamic mapping data. It is hoped that this freely provided data will aid in small molecule drug discovery efforts to defeat SARS-CoV-2.

An online repository of solvation thermodynamic and structural maps of SARS-CoV-2 targets.

SARS-CoV-2 recently jumped species and rapidly spread via human-to-human transmission to cause a global outbreak of COVID-19. The lack of effective vaccine combined with the severity of the disease necessitates attempts to develop small molecule drugs to combat the virus. COVID19_GIST_HSA is a freely available online repository to provide solvation thermodynamic maps of COVID-19-related protein small molecule drug targets. Grid Inhomogeneous Solvation Theory maps were generated using AmberTools cpptraj-GIST and Hydration Site Analysis maps were created using SSTmap code. The resultant data can be applied to drug design efforts: scoring solvent displacement for docking, rational lead modification, prioritization of ligand- and protein- based pharmacophore elements, and creation of water-based pharmacophores. Herein, we demonstrate the use of the solvation thermodynamic mapping data. It is hoped that this freely provided data will aid in small molecule drug discovery efforts to defeat SARS-CoV-2.

Ethnobotanical study on medicinal plants used by Maonan people in China.

BACKGROUND: This paper is based on an ethnobotanical investigation that focused on the traditional medicinal plants used by local Maonan people to treat human diseases in Maonan concentration regions. The Maonan people have relied on traditional medicine since ancient times, especially medicinal plants. The aim of this study is to document medicinal plants used by the Maonans and to report the status of medicinal plants and associated traditional knowledge. METHODS: Ethnobotanical data were collected from June 2012 to September 2014 in Huanjiang Maonan Autonomous County, northern Guangxi, southwest China. In total, 118 knowledgeable informants were interviewed. Following statistically sampling method, eighteen villages from 5 townships were selected to conduct field investigations. Information was collected through the approache of participatory observation, semi-structured interviews, ranking exercises, key informant interviews, focus group discussions, and participatory rural appraisals. RESULTS: A total of 368 medicinal plant species were investigated and documented together with their medicinal uses by the Maonans, most of which were obtained from the wild ecosystems. The plants were used to treat 95 human diseases. Grinding was a widely used method to prepare traditional herbal medicines. There were significant relationships between gender and age, and between gender and informants' knowledge of medicinal plant use. Deforestation for agricultural purposes was identified as the most destructive factor of medicinal plants, followed by drought and over-harvest. CONCLUSIONS: The species diversity of medicinal plants used by the Maonans in the study area was very rich. Medicinal plants played a significant role in healing various human disorders in the Maonan communities. However, the conflicts between traditional inheriting system and recent socio-economic changes (and other factors) resulted in the reduction or loss of both medicinal plants and associated indigenous knowledge. Thus, conservation efforts and policies, and innovation of inheriting system are necessary for protecting the medicinal plants and associated indigenous knowledge. Awareness is also needed to be raised among local Maonans focusing on sustainable utilization and management of both medicinal plants and traditional knowledge.