Displaying publications 1 - 20 of 242 in total

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  1. Tan TJ, Wang D, Moraru CI
    J Dairy Sci, 2014;97(8):4759-71.
    PMID: 24881794 DOI: 10.3168/jds.2014-7957
    The main challenge in microfiltration (MF) is membrane fouling, which leads to a significant decline in permeate flux and a change in membrane selectivity over time. This work aims to elucidate the mechanisms of membrane fouling in cold MF of skim milk by identifying and quantifying the proteins and minerals involved in external and internal membrane fouling. Microfiltration was conducted using a 1.4-μm ceramic membrane, at a temperature of 6±1°C, cross-flow velocity of 6m/s, and transmembrane pressure of 159kPa, for 90min. Internal and external foulants were extracted from a ceramic membrane both after a brief contact between the membrane and skim milk, to evaluate instantaneous adsorption of foulants, and after MF. Four foulant streams were collected: weakly attached external foulants, weakly attached internal foulants, strongly attached external foulants, and strongly attached internal foulants. Liquid chromatography coupled with tandem mass spectrometry analysis showed that all major milk proteins were present in all foulant streams. Proteins did appear to be the major cause of membrane fouling. Proteomics analysis of the foulants indicated elevated levels of serum proteins as compared with milk in the foulant fractions collected from the adsorption study. Caseins were preferentially introduced into the fouling layer during MF, when transmembrane pressure was applied, as confirmed both by proteomics and mineral analyses. The knowledge generated in this study advances the understanding of fouling mechanisms in cold MF of skim milk and can be used to identify solutions for minimizing membrane fouling and increasing the efficiency of milk MF.
  2. Wang D, Fu Y, Ashraf MA
    Open Med (Wars), 2015;10(1):425-433.
    PMID: 28352731 DOI: 10.1515/med-2015-0074
    Tagged Magnetic Resonance Imaging (MRI) is a noninvasive technique for examining myocardial function and deformation. Tagged MRI can also be used in quasi-static MR elastography to acquire strain maps of other biological soft tissues. Harmonic phase (HARP) provides automatic and rapid analysis of tagged MR images for the quantification and visualization of myocardial strain. We propose a new artifact reduction method in strain maps. Image intensity of the DC component is estimated and subtracted from spatial modulation of magnetization (SPAMM) tagged MR images. DC peak interference in harmonic phase extraction is greatly reduced after DC component subtraction. The proposed method is validated using both simulated and MR acquired tagged images. Strain maps are obtained with better accuracy and smoothness after DC component subtraction.
  3. Huang ZL, Wang DY, Zhang PC, Dong F, Yeoh KH
    Acta Otolaryngol, 2001 Oct;121(7):844-8.
    PMID: 11718250
    Acoustic rhinometry (AR) evaluates the geometry of the nasal cavity by measuring the minimum cross-sectional area (MCA) and nasal volume (V) by means of acoustic reflection. Understanding the normal and pathologic conditions of the internal nasal cavity using AR is important in the diagnosis of structural abnormalities in patients. The aim of this study was to investigate the normal range of AR parameters in healthy volunteers from three ethnic groups in Singapore: Chinese, Malay and Indian. We also attempted to evaluate the role of these measurements in the documentation of structural abnormalities in the nose. A total of 189 Singaporeans, aged > or = 18 years, were recruited from a nationwide survey study. They comprised 83 Chinese, 35 Malays and 71 Indians. Eighty-nine subjects had a rhinoscopically normal nose (Group 1), 77 had significant septal deviation (Group 2) and 23 had inferior turbinate hypertrophy (Group 3). AR was performed to measure the MCA at the anterior 1-5 cm from the nostril and the volume (V) between points at the nostril and 5 cm into the nose. A mean MCA (mMCA; equal to (L + R)/2) and a total volume (Vt; equal to L + R) were then calculated for each subject, where L and R refer to the measurements made for the left and right nostrils, respectively. The results showed that there was no statistically significant difference in mMCA (p = 0.80) and Vt (p = 0.60) among the three ethnic subgroups of Group 1. Statistically significant differences were found only between Groups 1 and 3 (p < 0.001 for both mMCA and Vt) and between Groups 2 and 3 (p = 0.001 for mMCA and p = 0.013 for Vt). Although there was no significant difference between Groups 1 and 2, significant differences in MCA (p = 0.001) and V (p = 0.040) were found between the narrower sides (smaller volume) and the wider sides in Group 2, indicating volume compensation between the nasal cavities. In conclusion, our study demonstrates that there is no significant difference in the normal range of AR measurements among Chinese, Malay and Indian ethnic groups. AR is able to determine the structural abnormality of the internal nasal cavity caused by septal deviation and inferior turbinate hypertrophy.
  4. Xie D, Zhang H, Wei H, Lin L, Wang D, Wang M
    Aquat Toxicol, 2023 May;258:106497.
    PMID: 36940520 DOI: 10.1016/j.aquatox.2023.106497
    The continuous fragmentation of plastics and release of synthetic nanoplastics from products have been aggravating nanoplastic pollution in the marine ecosystem. The carrier role of nanoplastics may increase the bioavailability and toxicity effects of toxic metals, e.g., mercury (Hg), which is of growing concern. Here, the copepod Tigriopus japonicus was exposed to polystyrene nanoplastics (PS NPs) and Hg (alone or combined) at environmental realistic concentrations for three generations (F0-F2). Then, Hg accumulation, physiological endpoints, and transcriptome were analyzed. The results showed that the copepod's reproduction was significantly inhibited under PS NPs or Hg exposure. The presence of PS NPs caused significantly higher Hg accumulation, lower survival, and lower offspring production in copepods relative to Hg exposure, suggesting an increased threat to the copepod's survivorship and health. From the molecular perspective, combined PS NPs and Hg caused a graver effect on the DNA replication, cell cycle, and reproduction pathways relative to Hg exposure, linking to lower levels of survivorship and reproduction. Taken together, this study provides an early warning of nanoplastic pollution for the marine ecosystem not only because of their adverse effect per se but also their carrier role for increasing Hg bioaccumulation and toxicity in copepods.
  5. Chu C, Liu D, Wang D, Hu S, Zhang Y
    Int J Immunopathol Pharmacol, 2023;37:3946320231211795.
    PMID: 37942552 DOI: 10.1177/03946320231211795
    BACKGROUND: The TP53 gene is estimated to be mutated in over 50% of tumors, with the majority of tumors exhibiting abnormal TP53 signaling pathways. However, the exploration of TP53 mutation-related LncRNAs in Hepatocellular carcinoma (HCC) remains incomplete. This study aims to identify such LncRNAs and enhance the prognostic accuracy for Hepatoma patients.

    MATERIAL AND METHODS: Differential gene expression was identified using the "limma" package in R. Prognosis-related LncRNAs were identified via univariate Cox regression analysis, while a prognostic model was crafted using multivariate Cox regression analysis. Survival analysis was conducted using Kaplan-Meier curves. The precision of the prognostic model was assessed through ROC analysis. Subsequently, the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm were executed on the TCGA dataset via the TIDE database. Fractions of 24 types of immune cell infiltration were obtained from NCI Cancer Research Data Commons using deconvolution techniques. The protein expression levels encoded by specific genes were obtained through the TPCA database.

    RESULTS: In this research, we have identified 85 LncRNAs associated with TP53 mutations and developed a corresponding signature referred to as TP53MLncSig. Kaplan-Meier analysis revealed a lower 3-year survival rate in high-risk patients (46.9%) compared to low-risk patients (74.2%). The accuracy of the prognostic TP53MLncSig was further evaluated by calculating the area under the ROC curve. The analysis yielded a 5-year ROC score of 0.793, confirming its effectiveness. Furthermore, a higher score for TP53MLncSig was found to be associated with an increased response rate to immune checkpoint blocker (ICB) therapy (p = .005). Patients possessing high-risk classification exhibited lower levels of P53 protein expression and higher levels of genomic instability.

    CONCLUSION: The present study aimed to identify and validate LncRNAs associated with TP53 mutations. We constructed a prognostic model that can predict chemosensitivity and response to ICB therapy in HCC patients. This novel approach sheds light on the role of LncRNAs in TP53 mutation and provides valuable resources for analyzing patient prognosis and treatment selection.

  6. Wang D, Zhang M, Law CL, Zhang L
    Food Chem, 2024 Jan 01;430:136990.
    PMID: 37536067 DOI: 10.1016/j.foodchem.2023.136990
    Using natural deep eutectic solvents (NDES) for green extraction of lentinan from shiitake mushroom is a high-efficiency method. However, empirical and trial-and-error methods commonly used to select suitable NDES are unconvincing and time-consuming. Conductor-like screening model for realistic solvation (COSMO-RS) is helpful for the priori design of NDES by predicting the solubility of biomolecules. In this study, 372 NDES were used to evaluate lentinan dissolution capability via COSMO-RS. The results showed that the solvent formed by carnitine (15 wt%), urea (40.8 wt%), and water (44.2 wt%) exhibited the best performance for the extraction of lentinan. In the extraction stage, an artificial neural network coupled with genetic algorithm (ANN-GA) was developed to optimize the extraction conditions and to analyze their interaction effects on lentinan content. Therefore, COSMO-RS and ANN-GA can be used as powerful tools for solvent screening and extraction process optimization, which can be extended to various bioactive substance extraction.
  7. Pathak M, Coombes AGA, Turner MS, Palmer C, Wang D, Steadman KJ
    J Pharm Sci, 2015 Dec;104(12):4217-4222.
    PMID: 26398713 DOI: 10.1002/jps.24652
    Polycaprolactone (PCL) matrices loaded with doxycycline were produced by rapidly cooling suspensions of the drug powder in PCL solution in acetone. Drug loadings of 5%, 10%, and 15% (w/w) of the PCL content were achieved. Exposure of doxycycline powder to matrix processing conditions in the absence of PCL revealed an endothermic peak at 65°C with the main peak at 167°C, suggesting solvatomorph formation. Rapid "burst release" of 24%-32% was measured within 24 h when matrices were immersed in simulated vaginal fluid (SVF) at 37°C, because of the presence of drug at or close to the matrix surface, which is further confirmed by scanning electron microscopy. Gradual release of 66%-76% of the drug content occurred over the following 14 days. SVF containing doxycycline released from drug-loaded PCL matrices retained 81%-90% antimicrobial activity compared with the nonformulated drug. The concentrations of doxycycline predicted to be released into vaginal fluid from a PCL matrix in the form of an intravaginal ring would be sufficient to kill Neisseria gonorrhoea and many other pathogens. These results indicate that PCL may be a suitable polymer for controlled intravaginal delivery of doxycycline for the treatment of sexually transmitted infections.
  8. Chen H, Zeng X, Zhou Y, Yang X, Lam SS, Wang D
    J Hazard Mater, 2020 07 15;394:122570.
    PMID: 32244145 DOI: 10.1016/j.jhazmat.2020.122570
    The removal of antibiotics and resistance genes in wastewater treatment plants has attracted widespread attention, but the potential role of residual antibiotics in the disposal of waste activated sludge (WAS) has not been clearly understood. In this study, the effect of roxithromycin (ROX) on volatile fatty acid (VFA) recovery from WAS anaerobic fermentation was investigated. The experimental results showed that ROX made a positive contribution to the production of VFAs. With the increase of ROX dosages from 0 to 100 mg/kg TSS, the maximum accumulation of VFAs increased from 295 to 610 mg COD/L. Mechanism studies revealed that ROX promoted the solubilization of WAS by facilitating the disruption of extracellular polymeric substances. In addition, ROX enhanced the activity of acetate kinase and inhibited the activities of α-glucosidase and coenzyme F420, and showed a stronger inhibitory effect on methane production than the hydrolysis process, thus resulting in an increase in VFA accumulation. These findings provide a new insight for the role of antibiotics in anaerobic fermentation of WAS.
  9. Wang D, Wong SI, Sunarso J, Xu M, Wang W, Ran R, et al.
    ACS Appl Mater Interfaces, 2021 May 05;13(17):20105-20113.
    PMID: 33886260 DOI: 10.1021/acsami.1c02502
    Hydrocarbon-fueled solid oxide fuel cells (SOFCs) that can operate in the intermediate temperature range of 500-700 °C represent an attractive SOFC device for combined heat and power applications in the industrial market. One of the ways to realize such a device relies upon exploiting an in situ steam reforming process in the anode catalyzed by an anti-carbon coking catalyst. Here, we report a new Ni and Ru bimetal-doped perovskite catalyst, Ba(Zr0.1Ce0.7Y0.1Yb0.1)0.9Ni0.05Ru0.05O3-δ (BZCYYbNRu), with enhanced catalytic hydrogen production activity on n-butane (C4H10), which can resist carbon coking over extended operation durations. Ru in the perovskite lattice inhibits Ni precipitation from perovskite, and the high water adsorption capacity of proton conducting perovskite improves the coking resistance of BZCYYbNRu. When BZCYYbNRu is used as a steam reforming catalyst layer on a Ni-YSZ-supported anode, the single fuel cell not only achieves a higher power density of 1113 mW cm-2 at 700 °C under a 10 mL min-1 C4H10 continuous feed stream at a steam to carbon (H2O/C) ratio of 0.5 but also shows a much better operational stability for 100 h at 600 °C compared with those reported in the literature.
  10. Huang K, Zhang Y, Han Z, Zhou X, Song Y, Wang D, et al.
    PMID: 33102246 DOI: 10.3389/fcimb.2020.00475
    The subgenotype B5 of EV-A71 is a widely circulating subgenotype that frequently spreads across the globe. Several outbreaks have occurred in nations, such as Malaysia, Thailand, Vietnam, and Japan. Appearing first in Taiwan, China, the subgenotype has been frequently reported in mainland of China even though no outbreaks have been reported so far. The current study reconstructed the migration of the B5 subgenotype of EV-A71 in China via phylogeographical analysis. Furthermore, we investigated its population dynamics in order to draw more credible inferences. Following a dataset cleanup of B5 subgenotype of EV-A71, we detected earlier B5 subgenotypes of EV-A71 sequences that had been circulating in Malaysia and Singapore since the year 2000, which was before the 2003 outbreak that occurred in Sarawak. The Bayesian inference indicated that the most recent common ancestor of B5 subgenotype EV-A71 appeared in September, 1994 (1994.75). With respect to the overall prevalence, geographical reconstruction revealed that the B5 subgenotype EV-A71 originated singly from single-source cluster and subsequently developed several active lineages. Based on a large amount of data that was accumulated, we conclude that the appearance of the B5 subgenotype of EV-A71 in mainland of China was mainly due to multiple migrations from different origins.
  11. Tan KS, Zhang Y, Liu L, Li S, Zou X, Zeng W, et al.
    PMID: 33662568 DOI: 10.1016/j.cbpb.2021.110590
    Cholinesterases act as bio scavengers to clear organophosphorus (OP) compounds and prodrugs. The butyrylcholinesterase (BChE) gene has been found in several types of teleost fish but this gene has yet to be identified in cyprinid fish. Indeed, BChE homologs have not been found in the zebrafish (Danio rerio) genomic database. Here, we demonstrate that BChE activity is present in zebrafish, in line with other groups' findings. Using in-gel native-PAGE enzymatic activity staining and LC-MS/MS technique, an atypical BChE-like protein was identified in zebrafish. The si:ch211-93f2.1 gene was cloned, and His-tagged recombinant protein was expressed using the Pichia yeast system. The purified protein (molecular weight ~ 180 kDa) showed BChE activity, and degraded acetylcholinesterase (ACh) at a higher rate than BCh. However, phylogram analysis shows that this novel cholinesterase shared an evolutionary origin with carboxylic esterase rather than BChE. The zebrafish BChE-like protein shares structural characteristics with cholinesterase and carboxylesterase. The 2-arachidonoylglycerol (2-AG), nicosulfuron, and triacetin exhibited a higher binding affinity to the zebrafish BChE-like protein than BCh and ACh. With the identification of BChE-like protein in zebrafish, this study could shed light on the origin of BChE and may contribute towards the development of a BChE knockout zebrafish model for sensitive drug or toxin screening.
  12. Zhang W, Li K, Guo J, Ma T, Wang D, Shi S, et al.
    Biotechnol Appl Biochem, 2021 Aug;68(4):896-901.
    PMID: 32822079 DOI: 10.1002/bab.2012
    Researches have proved that increasing level of prostate-specific antigen (PSA) is an indicator for the progression of prostate cancer. The present study was focused to determine the PSA level by using anti-PSA antibody conjugated iron oxide nanoparticles, as the probe immobilized on the gap-fingered electrode sensing surface. The detection limit and sensitivity were found at the level of 1.9 pg/mL on the linear regression curve (y = 1.6939x - 0.5671; R² = 0.9878). A dose-dependent liner range was found from 1.9 until 60 pg/mL. Further, PSA was spiked in human serum and did not affect the interaction of PSA and its antibody. This method of detection quantifies the level of PSA, which helps to diagnose prostate cancer at its earlier stage.
  13. Su H, Kanchanatip E, Wang D, Zheng R, Huang Z, Chen Y, et al.
    Waste Manag, 2020 Feb 01;102:520-527.
    PMID: 31765972 DOI: 10.1016/j.wasman.2019.11.018
    In China, waste sorting practice is not strictly followed, plastics, especially food packaging, are commonly mixed in food waste. Supercritical water gasification (SCWG) of unsorted food waste was conducted in this study, using model unsorted food waste by mixture of pure food waste and plastic. Different operating parameters including reaction temperature, residence time, and feedstock concentration were investigated. Moreover, the effect of three representative food additives namely NaCl, NaHCO3 and Na2CO3 were tested in this work. Finally, comparative analysis about SCWG of unsorted food waste, pure food waste, and plastic was studied. It was found that higher reaction temperature, longer residence time and lower feedstock concentration were advantageous for SCWG of unsorted food waste. Within the range of operating parameters in this study, when the feedstock concentration was 5 wt%, the highest H2 yield (7.69 mol/kg), H2 selectivity (82.11%), total gas yield (17.05 mol/kg), and efficiencies of SCWG (cold gas efficiency, gasification efficiency, carbon gasification efficiency, and hydrogen gasification efficiency) were obtained at 480 °C for 75 min. Also, the addition of food additives with Na+ promoted the SCWG of unsorted food waste. The Na2CO3 showed the best catalytic performance on enhancement of H2 and syngas production. This research demonstrated the positive effect of waste sorting on the SCWG of food waste, and provided novel results and information that help to overcome the problems in the process of food waste treatment and accelerate the industrial application of SCWG technology in the future.
  14. Bao R, Liu M, Wang D, Wen S, Yu H, Zhong Y, et al.
    Front Pharmacol, 2019;10:1464.
    PMID: 31920654 DOI: 10.3389/fphar.2019.01464
    Background:Eurycoma longifolia is a tropical medicinal plant belonging to Simaroubaceae distributed in South East Asia. The stems are traditionally used for the treatment of sexual insufficiency, fever, hypertension, and malaria. Furthermore, it has antidiabetic and anticancer activities. Recently, it has been reported to reduce uric acid, but the mechanism is unclear. Hypothesis/Purpose: The aim of this study is to explore the effect and mechanism of E. longifolia stem 70% ethanol extract (EL) and its active compounds on uric acid excretion. Study Design and Methods: Potassium oxonate (PO) induced hyperuricemia rats model and adenine-PO induced hyperuricemia mice model were used to evaluate the effects of EL. Ultraperformance liquid chromatography was used to determine the levels of plasma or serum uric acid and creatinine. Hematoxylin-eosin staining was applied to observe kidney pathological changes, and western blot was applied to detect protein expression levels of uric acid transporters. Effects of constituents on urate uptake were tested in hURAT1-expressing HEK293T cells. Results: EL significantly reduced serum and plasma uric acid levels at dosages of 100, 200, and 400 mg/kg in hyperuricemia rats and mice, increased the clearance rate of uric acid and creatinine, and improved the renal pathological injury. The protein expression levels of urate reabsorption transporter 1 (URAT1) and glucose transporter 9 were down-regulated, while sodium-dependent phosphate transporter 1 and ATP-binding cassette transporter G2 were up-regulated in the kidney after EL treatment. The quassinoids isolated from EL showed inhibitory effects on urate uptake in hURAT1-expressing HEK293T cells, and the effect of eurycomanol was further confirmed in vivo. Conclusion: Our findings revealed that EL significantly reduced blood uric acid levels, prevented pathological changes of kidney in PO induced hyperuricemia animal model, and improved renal urate transports. We partly clarified the mechanism was related to suppressing effect of URAT1 by quassinoid in EL. This study is the first to demonstrate that EL plays a role in hyperuricemia by promoting renal uric acid excretion.
  15. Tan KS, Wang D, Lu Z, Zhang Y, Li S, Lin Y, et al.
    Int J Mol Sci, 2021 Oct 06;22(19).
    PMID: 34639145 DOI: 10.3390/ijms221910806
    Heart failure is the end-stage of all cardiovascular diseases with a ~25% 5-year survival rate, and insufficient mitochondrial energy production to meet myocardial demand is the hallmark of heart failure. Mitochondrial components involved in the regulation of ATP production remain to be fully elucidated. Recently, roles of 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) in the pathophysiological processes of heart diseases have emerged, implicated by evidence that mitochondrial CNPase proteins are associated with mitochondrial integrity under metabolic stress. In this study, a zebrafish heart failure model was established, by employing antisense morpholino oligonucleotides and the CRISPR-Cas9 gene-editing system, which recapitulates heart failure phenotypes including heart dysfunction, pericardial edema, ventricular enlargement, bradycardia, and premature death. The translational implications of CNPase in the pathophysiological process of heart failure were tested in a pressure overload-induced heart hypertrophy model, which was carried out in rats through transverse abdominal aorta constriction (TAAC). AAV9-mediated myocardial delivery of CNPase mitigated the hypertrophic response through the specific hydrolysis of 2'-3'-cyclic nucleotides, supported by the decrease of cardiac hypertrophy and fibrosis, the integrity of mitochondrial ultrastructure, and indicators of heart contractility in the AAV9-TAAC group. Finally, the biometrics of a mitochondrial respiration assay carried out on a Seahorse cellular energy analyzer demonstrated that CNPase protects mitochondrial respiration and ATP production from AngII-induced metabolic stress. In summary, this study provides mechanistic insights into CNPase-2',3'-cyclic nucleotide metabolism that protects the heart from energy starvation and suggests novel therapeutic approaches to treat heart failure by targeting CNPase activity.
  16. Geng HC, Zhu HT, Yang WN, Wang D, Yang CR, Zhang YJ
    Bioorg Chem, 2021 09;114:105125.
    PMID: 34217976 DOI: 10.1016/j.bioorg.2021.105125
    The young leaves of Phyllanthus acidus (Euphorbiaceae) are commonly used as edible vegetables in Indonesia, Thailand, and India, and their water infusions as dieting aids for people trying to remain slim. However, it is regarded as a poisonous plant in Malaya, and current researches are insufficient to provide a conclusion on its toxicity and safety under large doses. In this study, we firstly found that the refined nonpolar extracts of P. acidus leaves showed significant cytotoxic effect against BEAS-2B and L02 normal cell lines with IC50 values of 2.15 and 1.64 mg/mL, respectively. Further bioactivity-guided isolation produced four new rare dichapetalins (pacidusins A-D) from the most active fraction. Their structures including absolute configurations were elucidated by extensive spectroscopic data and X-ray diffraction analysis. All the isolated dichapetalins exhibited moderate cytotoxicity against, BEAS-2B and L02 normal cell lines with IC50 values ranging from 12.44 to 22.55 μM, as well as five human cancer cell lines with IC50 values ranging from 3.38 to 22.38 μM. Furthermore, the content of the main dichapetalins in the leaves were determined by analytical HPLC, which showed that the leaves contained a very high amount of the four isolated dichapetalins with a total yield of 0.488 mg/g of dry plant material. These toxic dichapetalins may lead to adverse health effects in higher doses. Our findings indicate that the dichapetalin containing leaves may not be suitable for consumption in large quantities as food, but demonstrate their potency as anti-cancer agents for new drug discovery.
  17. Wang D, Tan KS, Zeng W, Li S, Wang Y, Xu F, et al.
    Life Sci, 2022 Mar 15;293:120336.
    PMID: 35065166 DOI: 10.1016/j.lfs.2022.120336
    AIMS: Individuals with nonalcoholic hepatosteatosis (NAFLD) have a worse atherogenic lipoprotein profile and are susceptible to cardiovascular diseases. The MEK-ERK signaling cascades are central regulators of the levels of LDL receptor (LDLR), a major determinant of circulating cholesterol. It is elusive how hepatic steatosis contributes to dyslipidemia, especially hypercholesterolemia.

    MAIN METHODS: The effects of BChE on signaling pathways were determined by immunoblotting in a BChE knockout hepatocyte cell line. DiI-LDL probe was used to explore the effect of BChE expression on LDL internalization. Co-immunoprecipitation and LC-MS were used to explore the interacting proteins with BChE. Finally, a hepatocyte-restricted BChE silencing mouse model was established by AAV8-Tbg-shRNA, and the hypercholesterolemia was induced by 65% kcal% high-fat, high-sucrose diet feeding.

    MAIN FINDINGS: Here we demonstrate that butyrylcholinesterase (BChE) governs the LDL receptor levels and LDL uptake capacity through the MEK-ERK signaling cascades to promote Ldlr transcription. BChE interacts and co-localizes with PRMT5, a protein methylation modifier controlling the ERK signaling. PRMT5 regulates LDLR-dependent LDL uptake and is a substrate of chaperone-mediated autophagy (CMA). BChE deficiency induces the PRTM5 degradation dependent on CMA activity, possibly through facilitating the HSC70 (Heat shock cognate 71 kDa) recognition of PRMT5. Remarkably, in vivo hepatocyte-restricted BChE silencing reduces plasma cholesterol levels substantially. In contrast, the BChE knockout mice are predisposed to hypercholesterolemia.

    SIGNIFICANCE: Taken together, these findings outline a regulatory role for the BChE-PRMT5-ERK-LDLR axis in hepatocyte cholesterol metabolism, and suggest that targeting liver BChE is an effective therapeutic strategy to treat hypercholesterolemia.

  18. Nguyen TH, Wang D, Rahman SU, Bai H, Yao X, Chen D, et al.
    Infect Genet Evol, 2021 06;90:104750.
    PMID: 33548490 DOI: 10.1016/j.meegid.2021.104750
    Rice tungro bacilliform virus (RTBV) belongs to genus Tungrovirus within the family Caulimoviridae harbors circular double-stranded DNA (dsDNA). Rice tungro disease (RTD) caused by RTBV, responsible for severe rice yield losses in South and Southeast Asia. Here, we performed a systematic evolutionary and codon usage bias (CUB) analysis of RTBV genome sequences. We analysed different bioinformatics techniques to calculate the nucleotide compositions, the relative synonymous codon usage (RSCU), and other indices. The results indicated slightly or low codon usage bias in RTBV isolates. Mutation and natural selection pressures have equally contributed to this low codon usage bias. Additionally, multiple factors such as host, geographical distribution also affect codon usage patterns in RTBV genomes. RSCU analysis revealed that RTBV shows mutation bias and prefers A and U ended codons to code amino acids. Codon usage patterns of RTBV were also found to be influenced by its host. This indicates that RTBV have evolved codon usage patterns that are specific to its host. The findings from this study are expected to increase our understanding of factors leading to viral evolution and fitness with respect to hosts and the environment.
  19. Cao Y, Lu Z, Wang D, Tan KS, Liu W, Wu Q, et al.
    Eur J Pharmacol, 2021 Nov 15;911:174539.
    PMID: 34599913 DOI: 10.1016/j.ejphar.2021.174539
    Ischemia heart disease, one of the lethal cardiovascular diseases, irreversibly impairs cardiac function and is recognized as the primary risk factor for mortality in industrialized countries. The myocardial ischemia treatment still faces a considerable degree of increasing unmet needs. Isosteviol sodium (STVNa) and its derivatives have been proven to effectively alleviate metabolic diseases, hypertension, and heart hypertrophy. Little is known about how STVNa confers the cardioprotective effect during acute myocardial ischemia (AMI). In the present study, a rat model of acute ST-segment-elevation myocardial ischemia by left anterior descending (LAD) ligation was established. Compared to the AMI model group, STVNa administration (4 mg/kg, twice a day) well preserved left ventricle function by ejection fraction (45.10 ± 10.39 vs. 73.64 ± 13.15, p = 0.0013) and fractional shortening (22.94 ± 6.28 vs. 44.00 ± 11.05, p = 0.0017). Further analysis shows that high-dose STVNa (4 mg/kg) significantly improved the hemodynamics in AMI rats, with LVSP (88.25 ± 12.78 vs 99.75 ± 5.10, p = 0.018), max dP/dt (2978.45 ± 832.46 vs 4048.56 ± 827.23, p = 0.096), LVEDP (19.88 ± 2.00 vs 22.26 ± 3.21, p = 0.04) and left ventricular relaxation time constant (Tau) (0.030 ± 0.006 vs 0.021 ± 0.004, p = 0.021). Mechanically, STVNa administration retained the myocardial levels of phosphorylated AMPK, and CPT1b. Moreover, STVNa significantly increased the total energy expenditure, and reduced fatty acid accumulation through mitochondrial oxidative phosphorylation, which was supported by the indirect calorimetry and cellular energy analysis. Taken together, these findings suggest that STVNa is a potential cardioprotection agent for ischemic cardiomyopathy, likely through improving energy homeostasis, left ventricular hemodynamics, and heart function.
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