Browsing by Author "Jheng, Jia-Rong"

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    Orally delivered perilla (Perilla frutescens) leaf extract effectively inhibits SARS-CoV-2 infection in a Syrian hamster model
    (Elsevier, 2022-06-15) Chin, Yuan-Fan; Tang, Wen-Fan; Chang, Yu-Hsiu; Chang, Tein-Yao; Lin, Wen-Chin; Lin, Chia-Yi; Yang, Chuen-Mi; Wu, Hsueh-Ling; Liu, Ping-Cheng; Sun, Jun-Ren; Hsu, Shu-Chen; Lee, Chia-Ying; Lu, Hsuan-Ying; Chang, Jia-Yu; Jheng, Jia-Rong; Chen, Cheng Cheung; Kau, Jyh-Hwa; Huang, Chih-Heng; Chiu, Cheng-Hsun; Hung, Yi-Jen; Tsai, Hui-Ping; Horng, Jim-Tong; Medicine, School of Medicine
    On analyzing the results of cell-based assays, we have previously shown that perilla (Perilla frutescens) leaf extract (PLE), a food supplement and orally deliverable traditional Chinese medicine approved by the Taiwan Food and Drug Administration, effectively inhibits SARS-CoV-2 by directly targeting virions. PLE was also found to modulate virus-induced cytokine expression levels. In this study, we explored the anti-SARS-CoV-2 activity of PLE in a hamster model by examining viral loads and virus-induced immunopathology in lung tissues. Experimental animals were intranasally challenged with different SARS-CoV-2 doses. Jugular blood samples and lung tissue specimens were obtained in the acute disease stage (3–4 post-infection days). As expected, SARS-CoV-2 induced lung inflammation and hemorrhagic effusions in the alveoli and perivascular areas; additionally, it increased the expression of several immune markers of lung injury – including lung Ki67-positive cells, Iba-1-positive macrophages, and myeloperoxidase-positive neutrophils. Virus-induced lung alterations were significantly attenuated by orally administered PLE. In addition, pretreatment of hamsters with PLE significantly reduced viral loads and immune marker expression. A purified active fraction of PLE was found to confer higher antiviral protection. Notably, PLE prevented SARS-CoV-2-induced increase in serum markers of liver and kidney function as well as the decrease in serum high-density lipoprotein and total cholesterol levels in a dose-dependent fashion. Differently from lung pathology, monitoring of serum biomarkers in Syrian hamsters may allow a more humane assessment of the novel drugs with potential anti-SARS-CoV-2 activity. Our results expand prior research by confirming that PLE may exert an in vivo therapeutic activity against SARS-CoV-2 by attenuating viral loads and lung tissue inflammation, which may pave the way for future clinical applications.
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    Plasma Proteomics Identifies B2M as a Regulator of Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction
    (Wolters Kluwer, 2024) Jheng, Jia-Rong; DesJardin, Jacqueline T.; Chen, Yi-Yun; Huot, Joshua R.; Bai, Yang; Cook, Todd; Hibbard, Lainey M.; Rupp, Jennifer M.; Fisher, Amanda; Zhang, Yingze; Duarte, Julio D.; Desai, Ankit A.; Machado, Roberto F.; Simon, Marc A.; Lai, Yen-Chun; Medicine, School of Medicine
    Background: Pulmonary hypertension (PH) represents an important phenotype in heart failure with preserved ejection fraction (HFpEF). However, management of PH-HFpEF is challenging because mechanisms involved in the regulation of PH-HFpEF remain unclear. Methods: We used a mass spectrometry-based comparative plasma proteomics approach as a sensitive and comprehensive hypothesis-generating discovery technique to profile proteins in patients with PH-HFpEF and control subjects. We then validated and investigated the role of one of the identified proteins using in vitro cell cultures, in vivo animal models, and independent cohort of human samples. Results: Plasma proteomics identified high protein abundance levels of B2M (β2-microglobulin) in patients with PH-HFpEF. Interestingly, both circulating and skeletal muscle levels of B2M were increased in mice with skeletal muscle SIRT3 (sirtuin-3) deficiency or high-fat diet-induced PH-HFpEF. Plasma and muscle biopsies from a validation cohort of PH-HFpEF patients were found to have increased B2M levels, which positively correlated with disease severity, especially pulmonary capillary wedge pressure and right atrial pressure at rest. Not only did the administration of exogenous B2M promote migration/proliferation in pulmonary arterial vascular endothelial cells but it also increased PCNA (proliferating cell nuclear antigen) expression and cell proliferation in pulmonary arterial vascular smooth muscle cells. Finally, B2m deletion improved glucose intolerance, reduced pulmonary vascular remodeling, lowered PH, and attenuated RV hypertrophy in mice with high-fat diet-induced PH-HFpEF. Conclusions: Patients with PH-HFpEF display higher circulating and skeletal muscle expression levels of B2M, the magnitude of which correlates with disease severity. Our findings also reveal a previously unknown pathogenic role of B2M in the regulation of pulmonary vascular proliferative remodeling and PH-HFpEF. These data suggest that circulating and skeletal muscle B2M can be promising targets for the management of PH-HFpEF.