Displaying publications 1 - 20 of 51 in total

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  1. ROS Stress and Cell Membrane Disruption are the Main Antifungal Mechanisms of 2-Phenylethanol against Botrytis cinerea
    Zou X, Wei Y, Jiang S, Xu F, Wang H, Zhan P, et al.
    J Agric Food Chem, 2022 Nov 16;70(45):14468-14479.
    PMID: 36322824 DOI: 10.1021/acs.jafc.2c06187
    2-Phenylethanol (2-PE), a common compound found in plants and microorganisms, exhibits broad-spectrum antifungal activity. Using Botrytis cinerea, we demonstrated that 2-PE suppressed mycelium growth in vitro and in strawberry fruit and reduced natural disease without adverse effects to fruit quality. 2-PE caused structural damage to mycelia, as shown by scanning and transmission electron microscopy. From RNA sequencing analysis we found significantly upregulated genes for enzymatic and nonenzymatic reactive oxygen species (ROS) scavenging systems including sulfur metabolism and glutathione metabolism, indicating that ROS stress was induced by 2-PE. This was consistent with results from assays demonstrating an increase ROS and hydrogen peroxide levels, antioxidant enzyme activities, and malondialdehyde content in treated cells. The upregulation of ATP-binding cassette transporter genes, the downregulation of major facilitator superfamily transporters genes, and the downregulation of ergosterol biosynthesis genes indicated a severe disruption of cell membrane structure and function. This was consistent with results from assays demonstrating compromised membrane integrity and lipid peroxidation. To summarize, 2-PE exposure suppressed B. cinerea growth through ROS stress and cell membrane disruption.
  2. Tryptophol Improves the Biocontrol Efficacy of Scheffersomyces spartinae against the Gray Mold of Strawberries by Quorum Sensing
    Zhao Z, Wei Y, Zou X, Jiang S, Chen Y, Ye J, et al.
    J Agric Food Chem, 2023 Dec 02.
    PMID: 38041637 DOI: 10.1021/acs.jafc.3c06676
    Previously, we reported that marine yeast Scheffersomyces spartinae exhibited biocontrol efficacy against the gray mold of strawberries caused by Botrytis cinerea. Herein, tryptophol, a quorum-sensing molecule, was identified in the metabolites of S. spartinae. Subsequently, we found that 25 μM tryptophol promoted population density, biofilm formation, and cell aggregation of S. spartinae. Furthermore, 25 μM tryptophol improved the biocontrol efficacy of S. spartinae against B. cinerea in vitro and in the strawberry fruit. Under a scanning electronic microscope, tryptophol facilitated colonization and biofilm formation on strawberry wounds, showing that tryptophol increased the biocontrol efficacy of S. spartinae via quorum sensing. Transcriptome analysis revealed that tryptophol upregulated the gene expression of SDS3, DAL81, DSE1, SNF5, SUN41, FLO8, and HOP1, which was associated with cell adhesion or biofilm formation. Thus, to the best of our knowledge, this study was the first to report that tryptophol improved the biocontrol efficacy of S. spartinae via quorum sensing.
  3. The regulation of Cytochrome f by mannose treatment in broccoli and its relationship with programmed cell death in tobacco BY-2 cells
    Zhao S, Chen J, Cao S, Wang H, Chen H, Wei Y, et al.
    Plant Physiol Biochem, 2024 Mar;208:108480.
    PMID: 38437751 DOI: 10.1016/j.plaphy.2024.108480
    It is well established that programmed cell death (PCD) occurred in broccoli during postharvest senescence, but no studies have been conducted on the regulation of broccoli cytochrome f by mannose treatment and its relationship with PCD. In this study, we treated broccoli buds with mannose to investigate the changes in color, total chlorophyll content, gene expression related to chlorophyll metabolism, chloroplast structure, and cytochrome f determination during postharvest storage. In addition, to investigate the effect of cytochrome f on PCD, we extracted cytochrome f from broccoli and treated Nicotiana tabacum L. cv Bright Yellow 2 (BY-2) cells with extracted cytochrome f from broccoli at various concentrations. The results showed that cytochrome f can induce PCD in tobacco BY-2 cells, as evidenced by altered cell morphology, nuclear chromatin disintegration, DNA degradation, decreased cell viability, and increased caspase-3-like protease production. Taken together, our study indicated that mannose could effectively delay senescence of postharvest broccoli by inhibiting the expression of gene encoding cytochrome f which could induce PCD.
  4. Engineering ellipsoidal cap-like hydrogel particles as building blocks or sacrificial templates for three-dimensional cell culture
    Zhang W, Huang G, Ng K, Ji Y, Gao B, Huang L, et al.
    Biomater Sci, 2018 Mar 07.
    PMID: 29511758 DOI: 10.1039/c7bm01186e
    Hydrogel particles that can be engineered to compartmentally culture cells in a three-dimensional (3D) and high-throughput manner have attracted increasing interest in the biomedical area. However, the ability to generate hydrogel particles with specially designed structures and their potential biomedical applications need to be further explored. This work introduces a method for fabricating hydrogel particles in an ellipsoidal cap-like shape (i.e., ellipsoidal cap-like hydrogel particles) by employing an open-pore anodic aluminum oxide membrane. Hydrogel particles of different sizes are fabricated. The ability to produce ellipsoidal cap-like magnetic hydrogel particles with controlled distribution of magnetic nanoparticles is demonstrated. Encapsulated cells show high viability, indicating the potential for using these hydrogel particles as structure- and remote-controllable building blocks for tissue engineering application. Moreover, the hydrogel particles are also used as sacrificial templates for fabricating ellipsoidal cap-like concave wells, which are further applied for producing size controllable cell aggregates. The results are beneficial for the development of hydrogel particles and their applications in 3D cell culture.
  5. PpBZR1, a BES/BZR transcription factor, enhances cold stress tolerance by suppressing sucrose degradation in peach fruit
    Zhang S, Cao K, Wei Y, Jiang S, Ye J, Xu F, et al.
    Plant Physiol Biochem, 2023 Sep;202:107972.
    PMID: 37611487 DOI: 10.1016/j.plaphy.2023.107972
    Brassinosteroids (BRs) are phytohormones that play numerous roles in a plant's response to environmental stress. While BES/BZR transcription factors are essential components in BR signaling, their role in regulating postharvest fruit responses to cold stress is largely unknown. In this study, the application of 24-epibrassinolide (EBR) to peaches alleviated chilling injury (CI) during postharvest cold storage. We further characterized a key BES/BZR gene, PpBZR1, which regulates peach cold resistance. Transient expression PpBZR1 in peaches showed that PpBZR1 inhibits PpVIN2 expression and VIN activity, resulting in an elevated level of sucrose, which protects fruit from CI. Arabidopsis thaliana expressing PpBZR1 that had a high germination and seedling survival rate at low temperatures, which may be due to higher level of sucrose and lower oxidative damage. Mechanistically, we confirmed that PpBZR1 directly binds to the PpVIN2 promoter and functions as a negative regulator for sucrose metabolism. In addition, PpCBF1/5/6 were induced by EBR treatment and AtCBFs were upregulated in PpBZR1 transgenic Arabidopsis thaliana. Combined with previous findings, we hypothesize that PpBZR1 regulates PpVIN2 and may also be mediated by CBF. In conclusion, PpBZR1 expression is induced by EBR treatment during cold storage, which futher inhibite sucrose degradation gene PpVIN2 transcription via direct binding its promoter and indirectly regulating PpVIN2, resulting in slower sucrose degradation and higher chilling tolerance of peach.
  6. Glutamate application maintains quality and antioxidant capacity of fresh-cut carrots by modulating GABA shunt, phenylpropanoid and ROS metabolism
    Zhang J, Zhao J, Zuo X, You W, Ru X, Xu F, et al.
    Food Chem, 2024 Jun 15;443:138545.
    PMID: 38306904 DOI: 10.1016/j.foodchem.2024.138545
    The effects of exogenous glutamate treatment on the quality attributes, γ-aminobutyric acid (GABA) shunt, phenylpropanoid pathway, and antioxidant capacity of fresh-cut carrots were investigated. Results showed that glutamate treatment suppressed the increases in lightness and whiteness values, inhibited the degradation of total carotenoids and maintained better flavor and taste in fresh-cut carrots. Moreover, glutamate treatment rapidly promoted the activities of glutamate decarboxylase and GABA transaminase, thus improving the GABA content. It also significantly enhanced the activities of phenylalanine ammonia-lyase, cinnamate-4-hydroxylase, and 4-coumarate coenzyme A ligase and promoted the accumulation of total phenolics as well as the main individual phenolic compounds, including chlorogenic and caffeic acid. In addition, glutamate application activated the reactive oxygen system-related enzyme including peroxidase, superoxide dismutase, ascorbate peroxidase, and catalase activities to maintain higher antioxidant capacity in fresh-cut carrots. These results demonstrated that exogenous glutamate treatment maintained better nutritional quality and alleviated color deterioration by accelerating the accumulation of GABA and phenolics and enhancing the antioxidant capacity in fresh-cut carrots.
  7. CmCML11 interacts with CmCAMTA5 to enhance γ-aminobutyric acid (GABA) accumulation by regulating GABA shunt in fresh-cut cantaloupe
    You W, Zhang J, Ru X, Xu F, Wu Z, Jin P, et al.
    Plant Physiol Biochem, 2024 Jan;206:108217.
    PMID: 38039581 DOI: 10.1016/j.plaphy.2023.108217
    The effect of calcium chloride (CaCl2) treatment on γ-aminobutyric acid (GABA) accumulation in fresh-cut cantaloupe and the involved mechanisms were investigated. The result showed that 1% (w/v) CaCl2 treatment increased GABA content and activities of glutamate decarboxylase (GAD) and succinate semialdehyde dehydrogenase (SSADH), while decreased glutamate (Glu) content and GABA transaminase (GABA-T) activities in fresh-cut cantaloupe. CmCML11 and CmCAMTA5 expressions of CaCl2-treated fruit increased by 187.4% and 165.6% than control fruit in the initial 6 h. Besides, expressions of GABA shunt genes, including CmGAD1, CmGAD2, CmGABA-T and CmSSADH were also up-regulated by CaCl2 treatment during early storage. Moreover, acting as a transcriptional activator, CmCAMTA5 could bind to the CG-box in promoters of CmGAD1, CmGABA-T and CmSSADH and activate their transcription. Furthermore, the interaction between CmCML11 and CmCAMTA5 could enhance the transcriptional activation on GABA shunt genes which were regulated by CmCAMTA5. Collectively, our findings revealed that CaCl2 treatment promoted GABA accumulation in fresh-cut cantaloupe via the combined effect of CmCML11 and CmCAMTA5 in the regulation of expressions of CmGAD1, CmGABA-T, and CmSSADH in GABA shunt.
  8. Exogenous chlorogenic acid inhibits quality deterioration in fresh-cut potato slices
    You W, Wang C, Zhang J, Ru X, Xu F, Wu Z, et al.
    Food Chem, 2024 Jul 15;446:138866.
    PMID: 38430769 DOI: 10.1016/j.foodchem.2024.138866
    Fresh-cut potatoes are prone to surface browning and physiological degradation. Chlorogenic acid (CGA), a natural phenolic antioxidant, has demonstrated preservative properties in various postharvest products. However, the underlying mechanisms of its application on maintaining quality remain unclear. Therefore, the effect of exogenous CGA treatment on quality deterioration of potato slices and the mechanisms involved were investigated. Results revealed CGA treatment retarded the browning coloration, suppressed microbial growth and inhibited the declines in starch, and ascorbic acid contents in potato slices. Meanwhile, the treatment activated the phenylpropanoid pathway but decreased the activities of phenolic decomposition-related enzymes such as polyphenol oxidase (PPO) and tyrosinase and downregulated StPPO expression. Moreover, the treated slices exhibited reduced accumulation of reactive oxygen species and increased activity of antioxidant enzymes. Additionally, they displayed enhanced 2,2-diphenyl-1-picrylhydrazyl radicals scavenging capacity and higher ATP levels. Therefore, these findings indicated that CGA treatment was effective for quality maintenance and antioxidant capacity enhancement in fresh-cut potatoes, thereby providing potential strategies for the preservation and processing of fresh-cut produce.
  9. Assessment of tumourigenic potential in long-term cryopreserved human adipose-derived stem cells
    Yong KW, Safwani WKZW, Xu F, Zhang X, Choi JR, Abas WABW, et al.
    J Tissue Eng Regen Med, 2017 08;11(8):2217-2226.
    PMID: 26756982 DOI: 10.1002/term.2120
    Cryopreservation represents an efficient way to preserve human mesenchymal stem cells (hMSCs) at early culture/passage, and allows pooling of cells to achieve sufficient cells required for off-the-shelf use in clinical applications, e.g. cell-based therapies and regenerative medicine. To fully apply cryopreserved hMSCs in a clinical setting, it is necessary to evaluate their biosafety, e.g. chromosomal abnormality and tumourigenic potential. To date, many studies have demonstrated that cryopreserved hMSCs display no chromosomal abnormalities. However, the tumourigenic potential of cryopreserved hMSCs has not yet been evaluated. In the present study, we cryopreserved human adipose-derived mesenchymal stem cells (hASCs) for 3 months, using a slow freezing method with various cryoprotective agents (CPAs), followed by assessment of the tumourigenic potential of the cryopreserved hASCs after thawing and subculture. We found that long-term cryopreserved hASCs maintained normal levels of the tumour suppressor markers p53, p21, p16 and pRb, hTERT, telomerase activity and telomere length. Further, we did not observe significant DNA damage or signs of p53 mutation in cryopreserved hASCs. Our findings suggest that long-term cryopreserved hASCs are at low risk of tumourigenesis. These findings aid in establishing the biosafety profile of cryopreserved hASCs, and thus establishing low hazardous risk perception with the use of long-term cryopreserved hASCs for future clinical applications. Copyright © 2016 John Wiley & Sons, Ltd.
  10. Cryopreservation of Human Mesenchymal Stem Cells for Clinical Applications: Current Methods and Challenges
    Yong KW, Wan Safwani WK, Xu F, Wan Abas WA, Choi JR, Pingguan-Murphy B
    Biopreserv Biobank, 2015 Aug;13(4):231-9.
    PMID: 26280501 DOI: 10.1089/bio.2014.0104
    Mesenchymal stem cells (MSCs) hold many advantages over embryonic stem cells (ESCs) and other somatic cells in clinical applications. MSCs are multipotent cells with strong immunosuppressive properties. They can be harvested from various locations in the human body (e.g., bone marrow and adipose tissues). Cryopreservation represents an efficient method for the preservation and pooling of MSCs, to obtain the cell counts required for clinical applications, such as cell-based therapies and regenerative medicine. Upon cryopreservation, it is important to preserve MSCs functional properties including immunomodulatory properties and multilineage differentiation ability. Further, a biosafety evaluation of cryopreserved MSCs is essential prior to their clinical applications. However, the existing cryopreservation methods for MSCs are associated with notable limitations, leading to a need for new or improved methods to be established for a more efficient application of cryopreserved MSCs in stem cell-based therapies. We review the important parameters for cryopreservation of MSCs and the existing cryopreservation methods for MSCs. Further, we also discuss the challenges to be addressed in order to preserve MSCs effectively for clinical applications.
  11. Fulltext Phenotypic and functional characterization of long-term cryopreserved human adipose-derived stem cells
    Yong KW, Pingguan-Murphy B, Xu F, Abas WA, Choi JR, Omar SZ, et al.
    Sci Rep, 2015;5:9596.
    PMID: 25872464 DOI: 10.1038/srep09596
    Cryopreservation represents an effective technique to maintain the functional properties of human adipose-derived stem cells (ASCs) and allows pooling of cells via long-term storage for clinical applications, e.g., cell-based therapies. It is crucial to reduce freezing injury during the cryopreservation process by loading the ASCs with the optimum concentration of suitable cryoprotective agents (CPAs). In this study, human ASCs were preserved for 3 months in different combinations of CPAs, including 1) 0.25 M trehalose; 2) 5% dimethylsulfoxide (DMSO); 3) 10% DMSO; 4) 5% DMSO + 20% fetal bovine serum (FBS); 5) 10% DMSO + 20% FBS; 6) 10% DMSO + 90% FBS. Interestingly, even with a reduction of DMSO to 5% and without FBS, cryopreserved ASCs maintained high cell viability comparable with standard cryomedium (10% DMSO + 90% FBS), with normal cell phenotype and proliferation rate. Cryopreserved ASCs also maintained their differentiation capability (e.g., to adipocytes, osteocytes and chondrocytes) and showed an enhanced expression level of stemness markers (e.g., NANOG, OCT-4, SOX-2 and REX-1). Our findings suggest that 5% DMSO without FBS may be an ideal CPA for an efficient long-term cryopreservation of human ASCs. These results aid in establishing standardized xeno-free long-term cryopreservation of human ASCs for clinical applications.
  12. Fulltext Mechanoregulation of cardiac myofibroblast differentiation: implications for cardiac fibrosis and therapy
    Yong KW, Li Y, Huang G, Lu TJ, Safwani WK, Pingguan-Murphy B, et al.
    Am J Physiol Heart Circ Physiol, 2015 Aug 15;309(4):H532-42.
    PMID: 26092987 DOI: 10.1152/ajpheart.00299.2015
    Cardiac myofibroblast differentiation, as one of the most important cellular responses to heart injury, plays a critical role in cardiac remodeling and failure. While biochemical cues for this have been extensively investigated, the role of mechanical cues, e.g., extracellular matrix stiffness and mechanical strain, has also been found to mediate cardiac myofibroblast differentiation. Cardiac fibroblasts in vivo are typically subjected to a specific spatiotemporally changed mechanical microenvironment. When exposed to abnormal mechanical conditions (e.g., increased extracellular matrix stiffness or strain), cardiac fibroblasts can undergo myofibroblast differentiation. To date, the impact of mechanical cues on cardiac myofibroblast differentiation has been studied both in vitro and in vivo. Most of the related in vitro research into this has been mainly undertaken in two-dimensional cell culture systems, although a few three-dimensional studies that exist revealed an important role of dimensionality. However, despite remarkable advances, the comprehensive mechanisms for mechanoregulation of cardiac myofibroblast differentiation remain elusive. In this review, we introduce important parameters for evaluating cardiac myofibroblast differentiation and then discuss the development of both in vitro (two and three dimensional) and in vivo studies on mechanoregulation of cardiac myofibroblast differentiation. An understanding of the development of cardiac myofibroblast differentiation in response to changing mechanical microenvironment will underlie potential targets for future therapy of cardiac fibrosis and failure.
  13. Fulltext Paracrine Effects of Adipose-Derived Stem Cells on Matrix Stiffness-Induced Cardiac Myofibroblast Differentiation via Angiotensin II Type 1 Receptor and Smad7
    Yong KW, Li Y, Liu F, Bin Gao, Lu TJ, Wan Abas WA, et al.
    Sci Rep, 2016 10 05;6:33067.
    PMID: 27703175 DOI: 10.1038/srep33067
    Human mesenchymal stem cells (hMSCs) hold great promise in cardiac fibrosis therapy, due to their potential ability of inhibiting cardiac myofibroblast differentiation (a hallmark of cardiac fibrosis). However, the mechanism involved in their effects remains elusive. To explore this, it is necessary to develop an in vitro cardiac fibrosis model that incorporates pore size and native tissue-mimicking matrix stiffness, which may regulate cardiac myofibroblast differentiation. In the present study, collagen coated polyacrylamide hydrogel substrates were fabricated, in which the pore size was adjusted without altering the matrix stiffness. Stiffness is shown to regulate cardiac myofibroblast differentiation independently of pore size. Substrate at a stiffness of 30 kPa, which mimics the stiffness of native fibrotic cardiac tissue, was found to induce cardiac myofibroblast differentiation to create in vitro cardiac fibrosis model. Conditioned medium of hMSCs was applied to the model to determine its role and inhibitory mechanism on cardiac myofibroblast differentiation. It was found that hMSCs secrete hepatocyte growth factor (HGF) to inhibit cardiac myofibroblast differentiation via downregulation of angiotensin II type 1 receptor (AT1R) and upregulation of Smad7. These findings would aid in establishment of the therapeutic use of hMSCs in cardiac fibrosis therapy in future.
  14. Soluble dietary fiber from Prunus persica dregs alleviates gut microbiota dysfunction through lead excretion
    Yao M, Guo X, Shao X, Wei Y, Zhang X, Wang H, et al.
    Food Chem Toxicol, 2023 May;175:113725.
    PMID: 36925041 DOI: 10.1016/j.fct.2023.113725
    Lead (Pb) can pollute the environment and food through air, water and other means, resulting in human exposure to lead pollution, and there is no threshold level of lead toxicity, even small doses of lead will have a range of harmful effects in humans. This study demonstrates for the first time that dietary addition of soluble dietary fiber (SDF) from Prunus persica dregs reduces lead bioaccumulation in mice, and eliminates lead through feces. Compared with lead-exposed mice, SDF supplementation effectively prevented lead-induced changes in colon tissue, and increased expression of tight junction proteins (ZO-1 and occludin). We analyzed the effects of SDF on gut microbiota and metabolites by a combination of 16S rRNA high-throughput sequencing and untargeted metabolomics. The results showed that SDF altered lead-induced perturbations in the layout and structure of the gut microbiota, including increased Desulfovibrio and Alistipes abundance and decreased Bacteroidetes abundance. Meanwhile, we also provide evidence that SDF supplementation alters the levels of amino acids, bile acids, and lipids in the gut, and that these metabolites are closely associated with microbiota with good lead binding capacity. Therefore, we speculate that SDF has the potential to provide a protective effect against intestinal damage by promoting lead excretion.
  15. Vale Professor Xiaoxian Liu
    Xu F, Binns C, Low WY
    Asia Pac J Public Health, 2020 5 16;32(2-3):134-135.
    PMID: 32410510 DOI: 10.1177/1010539520915009
  16. Fulltext Effects of tai chi on postural balance and quality of life among the elderly with gait disorders: A systematic review
    Xu F, Soh KG, Chan YM, Bai XR, Qi F, Deng N
    PLoS One, 2023;18(9):e0287035.
    PMID: 37768953 DOI: 10.1371/journal.pone.0287035
    BACKGROUND: Tai Chi is good for improving the physical fitness of older adults. But few studies have reported the effects of Tai Chi on the postural balance and quality of life of older adults with gait disorders.

    OBJECTIVE: This review aimed to assess the influence of tai chi on postural stability and quality of life in older adults with abnormal gait.

    METHOD: According to the literature retrieval principles, the works published from the inception date to May 2023 were retrieved, including the following databases: PubMed, Scopus, Web of Science, China National Knowledge Infrastructure, EBSCOhost, and Google Scholar. Subsequently, literature screening and quality assessment were performed.

    RESULTS: A total of 16 randomized controlled trials were included in this study, Tai Chi intervention can affect populations with Parkinson's disease (PD), no exercise, mild cognitive impairment (MCI), chronic stroke, sedentary, fear of falling, or history of falling. Postural instability is associated with balance, gait, the Unified Parkinson's Disease Rating Scale Motor Subscale 3 (UPDRS III), mobility, lower body strength, and falls. Only two articles looked at quality of life. The Yang style is the most commonly used in the intervention. Nonetheless, most studies were performed on female participants, hence, more research on older male populations is needed.

    CONCLUSION: Tai Chi intervention benefits postural balance in patients with gait disorders. 12 weeks is the most common intervention period for patients with gait disorders. The frequency of intervention is seven articles twice a week, and the intervention time is about 60 minutes. The Tai Chi intervention methods in this study involve Yang Style, Sun Style, Taoist Tai Chi, and Health Qigong Tai Chi, but the Yang Style Tai Chi intervention is the most widely used.

  17. Fulltext Comparative Analysis of Pediatric COVID-19 Infection in Southeast Asia, South Asia, Japan, and China
    Wong JJM, Abbas Q, Chuah SL, Malisie RF, Pon KM, Katsuta T, et al.
    Am J Trop Med Hyg, 2021 Jun 15;105(2):413-420.
    PMID: 34129517 DOI: 10.4269/ajtmh.21-0299
    There is a scarcity of data regarding coronavirus disease 2019 (COVID-19) infection in children from southeast and south Asia. This study aims to identify risk factors for severe COVID-19 disease among children in the region. This is an observational study of children with COVID-19 infection in hospitals contributing data to the Pediatric Acute and Critical Care COVID-19 Registry of Asia. Laboratory-confirmed COVID-19 cases were included in this registry. The primary outcome was severity of COVID-19 infection as defined by the World Health Organization (WHO) (mild, moderate, severe, or critical). Epidemiology, clinical and laboratory features, and outcomes of children with COVID-19 are described. Univariate and multivariable logistic regression models were used to identify risk factors for severe/critical disease. A total of 260 COVID-19 cases from eight hospitals across seven countries (China, Japan, Singapore, Malaysia, Indonesia, India, and Pakistan) were included. The common clinical manifestations were similar across countries: fever (64%), cough (39%), and coryza (23%). Approximately 40% of children were asymptomatic, and overall mortality was 2.3%, with all deaths reported from India and Pakistan. Using the multivariable model, the infant age group, presence of comorbidities, and cough on presentation were associated with severe/critical COVID-19. This epidemiological study of pediatric COVID-19 infection demonstrated similar clinical presentations of COVID-19 in children across Asia. Risk factors for severe disease in children were age younger than 12 months, presence of comorbidities, and cough at presentation. Further studies are needed to determine whether differences in mortality are the result of genetic factors, cultural practices, or environmental exposures.
  18. Risk Stratification in Pediatric Acute Respiratory Distress Syndrome: A Multicenter Observational Study
    Wong JJ, Phan HP, Phumeetham S, Ong JSM, Chor YK, Qian S, et al.
    Crit Care Med, 2017 Jul 26.
    PMID: 28749854 DOI: 10.1097/CCM.0000000000002623
    OBJECTIVES: The Pediatric Acute Lung Injury Consensus Conference developed a pediatric specific definition for acute respiratory distress syndrome (PARDS). In this definition, severity of lung disease is stratified into mild, moderate, and severe groups. We aim to describe the epidemiology of patients with PARDS across Asia and evaluate whether the Pediatric Acute Lung Injury Consensus Conference risk stratification accurately predicts outcome in PARDS.

    DESIGN: A multicenter, retrospective, descriptive cohort study.

    SETTING: Ten multidisciplinary PICUs in Asia.

    PATIENTS: All mechanically ventilated children meeting the Pediatric Acute Lung Injury Consensus Conference criteria for PARDS between 2009 and 2015.

    INTERVENTIONS: None.

    MEASUREMENTS AND MAIN RESULTS: Data on epidemiology, ventilation, adjunct therapies, and clinical outcomes were collected. Patients were followed for 100 days post diagnosis of PARDS. A total of 373 patients were included. There were 89 (23.9%), 149 (39.9%), and 135 (36.2%) patients with mild, moderate, and severe PARDS, respectively. The most common risk factor for PARDS was pneumonia/lower respiratory tract infection (309 [82.8%]). Higher category of severity of PARDS was associated with lower ventilator-free days (22 [17-25], 16 [0-23], 6 [0-19]; p < 0.001 for mild, moderate, and severe, respectively) and PICU free days (19 [11-24], 15 [0-22], 5 [0-20]; p < 0.001 for mild, moderate, and severe, respectively). Overall PICU mortality for PARDS was 113 of 373 (30.3%), and 100-day mortality was 126 of 317 (39.7%). After adjusting for site, presence of comorbidities and severity of illness in the multivariate Cox proportional hazard regression model, patients with moderate (hazard ratio, 1.88 [95% CI, 1.03-3.45]; p = 0.039) and severe PARDS (hazard ratio, 3.18 [95% CI, 1.68, 6.02]; p < 0.001) had higher risk of mortality compared with those with mild PARDS.

    CONCLUSIONS: Mortality from PARDS is high in Asia. The Pediatric Acute Lung Injury Consensus Conference definition of PARDS is a useful tool for risk stratification.

  19. Fulltext Calcium Involved in the Enrichment of γ-Aminobutyric Acid (GABA) in Broccoli Sprouts under Fructose Treatment
    Wei Q, Xie K, Wang H, Shao X, Wei Y, Chen Y, et al.
    Plants (Basel), 2023 Jan 04;12(2).
    PMID: 36678938 DOI: 10.3390/plants12020224
    The effect of fructose on γ-aminobutyric acid (GABA) content and its metabolic pathway in broccoli sprouts was investigated. The results demonstrated that the fructose treatment not only significantly increased the fresh weight, GABA, and glutamate contents in sprouts, but also promoted the activity of glutamic acid decarboxylase (GAD) and the expressions of BoGAD1 and BoGAD2. Meanwhile, fructose treatment inhibited the stem length of broccoli sprouts and enhanced the abscisic acid (ABA) production in comparison with the control. Ca2+, CaM contents, and BoCaM2 expression in broccoli sprouts were also stimulated after fructose treatment. Exogenous fructose increased inositol trisphosphate (IP3) content and activated the activity of phosphatidylinositol-specific phospholipase C (PI-PLC) and the expression of BoPLC2, contributing to Ca2+ influx into the cells. These results suggested that Ca2+ played an essential role in GABA enrichment under fructose treatment, which may be associated with GAD and PI-PLC.
  20. Ethyl cinnamate suppresses tumor growth through anti-angiogenesis by attenuating VEGFR2 signal pathway in colorectal cancer
    Wang S, Yang J, Kuang X, Li H, Du H, Wu Y, et al.
    J Ethnopharmacol, 2024 May 23;326:117913.
    PMID: 38360380 DOI: 10.1016/j.jep.2024.117913
    ETHNOPHARMACOLOGICAL RELEVANCE: Kaempferia galanga Linn. is an aromatic medicinal herb with extensively applied in India, China, Malaysia and other South Asia countries for thousands of years. It has been mentioned to treat abdominal tumors. Ethyl cinnamate (EC), one of the main chemical constituents of the rhizome of K. galanga, exhibited nematocidal, sedative and vasorelaxant activities. However, its anti-angiogenic activity, and anti-tumor effect have not been investigated.

    AIM OF THE STUDY: To investigate the anti-angiogenic mechanism of EC and its anti-tumor effect by suppressing angiogenesis.

    MATERIALS AND METHODS: The in vitro anti-angiogenic effect was evaluated using HUVECs model induced by VEGF and zebrafish model in vivo. The influence of the EC on phosphorylation of VEGFR2 and its downstream signaling pathways were evaluated by western blotting assay. Molecule docking technology was conducted to explore the interaction between EC and VEGFR2. SPR assay was used for detecting the binding affinity between EC and VEGFR2. To further investigate the molecular mechanism of EC on anti-angiogenesis, VEGFR2 knockdown in HUVECs and examined the influence of the EC. Anti-tumor activity of EC was evaluated using colony formation assay and apoptosis assay. The inhibitory effect of EC on tumor growth was explored using HT29 colon cancer xenograft model.

    RESULTS: EC obviously inhibited proliferation, migration, invasion and tube formation of VEGF-induced HUVECs. EC also induced apoptosis of HUVECs. Moreover, it inhibited the development of vessel formation in zebrafish. Further investigations demonstrated that EC could suppress the phosphorylation of VEGFR2, and its downstream signaling pathways were altered in VEGF-induced HUVECs. EC formed a hydrogen bond to bind with the ATP binding site of the VEGFR2, and EC-VEGFR2 interaction was shown in SPR assay. The suppressive effect of EC on angiogenesis was abrogated after VEGFR2 knockdown in HUVECs. EC inhibited the colon cancer cells colony formation and induced apoptosis. In addition, EC suppressed tumor growth in colon cancer xenograft model, and no detectable hepatotoxicity and nephrotoxicity. In addition, it inhibited the phosphorylation of VEGFR2, and its downstream signal pathways in tumor.

    CONCLUSIONS: EC could inhibit tumor growth in colon cancer by suppressing angiogenesis via VEGFR2 signaling pathway, and suggested EC as a promising candidate for colon cancer treatment.

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